vitamin-k-semiquinone-radical and Vitamin-K-Deficiency

Vitamin K is essential for the process of coagulation. In its absence, severe and sometimes fatal bleeding events can occur, especially in newborns. Vitamin K prophylaxis at birth has been shown to prevent morbidity and mortality associated with vitamin K deficiency bleeding (VKDB) and is recommended by multiple organizations including the American Academy of Pediatrics and the World Health Organization. Pediatricians should feel comfortable explaining the risks and benefits of vitamin K prophylaxis to families and should be equipped to recognize signs of VKDB, especially given increasing rates of parental refusal. This article aims to improve understanding of VKDB, including prevention, early recognition, and treatment.

Topics: Child; Hemorrhage; Humans; Infant, Newborn; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Vitamin K occupies a unique and often obscured place among its fellow fat-soluble vitamins. Evidence is mounting, however, that vitamin K (VK) may play an important role in the visual system apart from the hepatic carboxylation of hemostatic-related proteins. However, to our knowledge, no review covering the topic has appeared in the medical literature. Recent studies have confirmed that matrix Gla protein (MGP), a vitamin K-dependent protein (VKDP), is essential for the regulation of intraocular pressure in mice. The PREDIMED (Prevención con Dieta Mediterránea) study, a randomized trial involving 5860 adults at risk for cardiovascular disease, demonstrated a 29% reduction in the risk of cataract surgery in participants with the highest tertile of dietary vitamin K1 (PK) intake compared with those with the lowest tertile. However, the specific requirements of the eye and visual system (EVS) for VK, and what might constitute an optimized VK status, is currently unknown and largely unexplored. It is, therefore, the intention of this narrative review to provide an introduction concerning VK and the visual system, review ocular VK biology, and provide some historical context for recent discoveries. Potential opportunities and gaps in current research efforts will be touched upon in the hope of raising awareness and encouraging continued VK-related investigations in this important and highly specialized sensory system.

Topics: Animals; Mice; Sense Organs; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency; Vitamins

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Humans; Hyperargininemia; Vitamin K; Vitamin K Deficiency

Vitamin K (VK) plays many important functions in the body. The most important of them include the contribution in calcium homeostasis and anticoagulation. Vascular calcification (VC) is one of the most important mechanisms of renal pathology. The most potent inhibitor of this process-matrix Gla protein (MGP) is VK-dependent. Chronic kidney disease (CKD) patients, both non-dialysed and hemodialysed, often have VK deficiency. Elevated uncarboxylated matrix Gla protein (ucMGP) levels indirectly reflected VK deficiency and are associated with a higher risk of cardiovascular events in these patients. It has been suggested that VK intake may reduce the VC and related cardiovascular risk. Vitamin K intake has been suggested to reduce VC and the associated cardiovascular risk. The role and possibility of VK supplementation as well as the impact of anticoagulation therapy on VK deficiency in CKD patients is discussed.

Topics: Anticoagulants; Blood Coagulation; Bone and Bones; Calcium; Calcium-Binding Proteins; Cardiovascular Diseases; Extracellular Matrix Proteins; Humans; Matrix Gla Protein; Renal Dialysis; Renal Insufficiency, Chronic; Vascular Calcification; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

Chronic kidney disease (CKD) is commonly associated with vitamin K deficiency. Some of the serious complications of CKD are represented by cardiovascular disease (CVD) and skeletal fragility with an increased risk of morbidity and mortality. A complex pathogenetic link between hormonal and ionic disturbances, bone tissue and metabolism alterations, and vascular calcification (VC) exists and has been defined as chronic kidney disease-mineral and bone disorder (CKD-MBD). Poor vitamin K status seems to have a key role in the progression of CKD, but also in the onset and advance of both bone and cardiovascular complications. Three forms of vitamin K are currently known: vitamin K1 (phylloquinone), vitamin K2 (menaquinone), and vitamin K3 (menadione). Vitamin K plays different roles, including in activating vitamin K-dependent proteins (VKDPs) and in modulating bone metabolism and contributing to the inhibition of VC. This review focuses on the biochemical and functional characteristics of vitamin K vitamers, suggesting this nutrient as a possible marker of kidney, CV, and bone damage in the CKD population and exploring its potential use for promoting health in this clinical setting. Treatment strategies for CKD-associated osteoporosis and CV disease should include vitamin K supplementation. However, further randomized clinical studies are needed to assess the safety and the adequate dosage to prevent these CKD complications.

Topics: Bone and Bones; Cardiovascular Diseases; Chronic Kidney Disease-Mineral and Bone Disorder; Female; Humans; Male; Renal Insufficiency, Chronic; Vascular Calcification; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

This narrative review aimed to summarize the current evidence on the connection between dysbiosis and vitamin K deficiency in patients with chronic kidney disease (CKD). The presence of dysbiosis (perturbations in the composition of the microbiota) has been described in several non-communicable diseases, including chronic kidney disease, and it has been hypothesized that dysbiosis may cause vitamin K deficiency. Patients with CKD present both vitamin K deficiency and gut dysbiosis; however, the relationship between gut dysbiosis and vitamin K deficiency remains to be addressed.. Recently, few studies in animals have demonstrated that a dysbiotic environment is associated with low production of vitamin K by the gut microbiota. Vitamin K plays a vital role in blood coagulation as well as in the cardiovascular and bone systems. It serves as a cofactor for γ-glutamyl carboxylases and thus is essential for the post-translational modification and activation of vitamin K-dependent calcification regulators, such as osteocalcin, matrix Gla protein, Gla-rich protein, and proteins C and S. Additionally, vitamin K executes essential antioxidant and anti-inflammatory functions. Dietary intake is the main source of vitamin K; however, it also can be produced by gut microbiota. This review discusses the effects of uremia on the imbalance in gut microbiota, vitamin K-producing bacteria, and vitamin K deficiency in CKD patients, leading to a better understanding and raising hypothesis for future clinical studies.

Topics: Animals; Dysbiosis; Humans; Renal Insufficiency, Chronic; Uremia; Vitamin K; Vitamin K Deficiency

Intestinal diseases, such as inflammatory bowel diseases (IBDs) and colorectal cancer (CRC) generally characterized by clinical symptoms, including malabsorption, intestinal dysfunction, injury, and microbiome imbalance, as well as certain secondary intestinal disease complications, continue to be serious public health problems worldwide. The role of vitamin K (VK) on intestinal health has drawn growing interest in recent years. In addition to its role in blood coagulation and bone health, several investigations continue to explore the role of VK as an emerging novel biological compound with the potential function of improving intestinal health. This study aims to present a thorough review on the bacterial sources, intestinal absorption, uptake of VK, and VK deficiency in patients with intestinal diseases, with emphasis on the effect of VK supplementation on immunity, anti-inflammation, intestinal microbes and its metabolites, antioxidation, and coagulation, and promoting epithelial development. Besides, VK-dependent proteins (VKDPs) are another crucial mechanism for VK to exert a gastroprotection role for their functions of anti-inflammation, immunomodulation, and anti-tumorigenesis. In summary, published studies preliminarily show that VK presents a beneficial effect on intestinal health and may be used as a therapeutic drug to prevent/treat intestinal diseases, but the specific mechanism of VK in intestinal health has yet to be elucidated.

Topics: Colorectal Neoplasms; Gastrointestinal Microbiome; Humans; Inflammatory Bowel Diseases; Intestinal Mucosa; Vitamin K; Vitamin K Deficiency

In Chronic Kidney Disease, vascular calcification (VC) is highly prevalent even at early stages and is gradually enhanced, along with disease progression to End-Stage Renal Disease (ESRD). The calcification pattern in uremia includes all types of mineralization and contributes to the heavy cardiovascular (CV) burden that is common in these patients. Ectopic mineralization is the result of the imbalance between inhibitors and promoters of vascular calcification, with the latter overwhelming the former. The most powerful, natural inhibitor of calcification is Matrix Gla Protein (MGP), a small vitamin K dependent protein, secreted by chondrocytes and vascular smooth muscle cells. In uremia, MGP was reported as the only molecule able to reverse VC by "sweeping" calcium and hydroxyapatite crystals away from the arterial wall. To become biologically active, this protein needs to undergo carboxylation and phosphorylation, reactions highly dependent on vitamin K status. The inactive form of MGP reflects the deficiency of vitamin K and has been associated with CV events and mortality in ESRD patients. During the past decade, vitamin K status has emerged as a novel risk factor for vascular calcification and CV disease in various populations, including dialysis patients. This review presents evidence regarding the association between vitamin K and CV disease in ESRD patients, which are prone to atherosclerosis and atheromatosis.

Topics: Animals; Blood Vessels; Calcium-Binding Proteins; Extracellular Matrix Proteins; Humans; Kidney Failure, Chronic; Matrix Gla Protein; Risk Factors; Signal Transduction; Treatment Outcome; Vascular Calcification; Vitamin K; Vitamin K Deficiency

Vascular calcification is a common and important cardiovascular risk factor in patients with chronic kidney disease (CKD). Recent advances in the understanding of the biology of vascular calcification implicate vitamin K-dependent proteins as important regulators in this process. This review highlights recent key advances in vascular biology, epidemiology, and clinical trials in this rapidly evolving field.. Vitamin K deficiency is associated with increasing severity of vascular calcification among patients with CKD, but the relationship with cardiovascular disease and mortality is inconsistent. Vitamin K may reduce calcification propensity by improving the activity of vitamin K-dependent calcification inhibitors or by down-regulating components of the innate immune system to reduce inflammation. However, recent randomized controlled trials in patients with diabetes, CKD, renal transplant, and on hemodialysis have failed to demonstrate improvement in vascular calcification or stiffness after vitamin K treatment.. Current evidence does not support a clinically useful role for vitamin K supplementation to prevent or reverse vascular calcification in patients with CKD. Knowledge gaps remain, particularly whether higher doses of vitamin K, longer duration of supplementations, or use a vitamin K as a part of a package of measures to counteract vascular calcification might be effective.

Topics: Humans; Renal Dialysis; Renal Insufficiency, Chronic; Vascular Calcification; Vitamin K; Vitamin K Deficiency

Vitamin K, well known for its role in coagulation, encompasses 2 major subgroups: vitamin K1 is exclusively synthesized by plants, whereas vitamin K2 mostly originates from bacterial synthesis. Vitamin K serves as a cofactor for the enzyme γ-glutamyl carboxylase, which carboxylates and thereby activates various vitamin K-dependent proteins. Several vitamin K-dependent proteins are synthesized in bone, but the role of vitamin K for bone health in chronic kidney disease patients, in particular the prevention of osteoporosis, is still not firmly established. Herein, we focus on another prominent action of vitamin K, in particular vitamin K2 (namely, the activation of matrix γ-carboxyglutamic acid protein, the most potent inhibitor of cardiovascular calcifications). Multiple observational studies link relative vitamin K deficiency or low intake to cardiovascular calcification progress, morbidity, and mortality. Patients with advanced chronic kidney disease are particularly vitamin K deficient, in part because of dietary restrictions but possibly also due to impaired endogenous recycling of vitamin K. At the same time, this population is characterized by markedly accelerated cardiovascular calcifications and mortality. High-dose dietary supplementation with vitamin K2, in particular the most potent form, menaquinone 7, can potently reduce circulating levels of dephosphorylated uncarboxylated (i.e., inactive matrix γ-carboxyglutamic acid protein) in patients with end-stage kidney disease. However, despite this compelling data basis, several randomized controlled trials with high-dose menaquinone 7 supplements in patients with advanced chronic kidney disease have failed to confirm cardiovascular benefits. Herein, we discuss potential reasons and solutions for this.

Topics: Humans; Renal Dialysis; Renal Insufficiency, Chronic; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

Vitamin K (VK) is a ligand of the pregnane X receptor (PXR), which plays a critical role in the detoxification of xenobiotics and metabolism of bile acids. VK

Topics: Animals; Bile Acids and Salts; Cholestasis, Intrahepatic; Dietary Supplements; Humans; Mice; Pregnane X Receptor; Vitamin K; Vitamin K Deficiency

Vitamin K is a key cofactor for the activation of proteins involved in blood coagulation, apoptosis, bone mineralization regulation, and vessel health. Scientific evidence shows an important role of activated osteocalcin and matrix-Gla protein in bone and vessels, markedly affected along the course of chronic kidney disease (CKD). In fact, CKD corresponds to an unique condition of vitamin K deficiency caused by dietary restriction, intestinal dysfunction, and impaired vitamin K recycling. Clinical data suggest that vitamin K status can be modulated and this prompts us to speculate whether patients with CKD might benefit from vitamin K supplementation. However, as important as whether the improvement in vitamin K status would be able to result in better bone quality, less vascular calcification, and lower mortality rates, several issues need to be clarified. These include better standardized methods for measuring vitamin K levels, and definition of the optimal concentration range for supplementation in different subgroups. Here, we review the literature data concerning the impact of vitamin K deficiency and supplementation on CKD-associated mineral and bone disorders (CKD-MBD). We present and discuss the available evidence from basic science and clinical studies, and highlight perspectives for further research.

Topics: Chronic Kidney Disease-Mineral and Bone Disorder; Humans; Molecular Structure; Vitamin K; Vitamin K Deficiency

Vitamin K is a cofactor of γ-glutamyl carboxylase, which plays an important role in the activation of γ-carboxyglutamate (gla)-containing proteins that negatively regulate calcification. Thus, vitamin K status might be associated with osteoarthritis (OA), in which cartilage calcification plays a role in the pathogenesis of the disease. This review collates the evidence on the relationship between vitamin K status (circulating or dietary intake level of vitamin K, or circulating uncarboxylated gla proteins) and OA from human observational studies and clinical trial, to examine its potential as an agent in preventing OA. The current literature generally agrees that a sufficient level of vitamin K is associated with a lower risk of OA and pathological joint features. However, evidence from clinical trials is limited. Mechanistic study shows that vitamin K activates matrix gla proteins that inhibit bone morphogenetic protein-mediated cartilage calcification. Gla-rich proteins also inhibit inflammatory cascade in monocytic cell lines, but this function might be independent of vitamin K-carboxylation. Although the current data are insufficient to establish the optimal dose of vitamin K to prevent OA, ensuring sufficient dietary intake seems to protect the elderly from OA.

Topics: Biomarkers; Calcium; Dietary Supplements; Disease Susceptibility; Humans; Osteoarthritis; Population Surveillance; Vitamin K; Vitamin K Deficiency

Chronic kidney disease (CKD) patients have a higher risk of cardiovascular (CVD) morbidity and mortality compared to the general population. The links between CKD and CVD are not fully elucidated but encompass both traditional and uremic-related risk factors. The term CKD-mineral and bone disorder (CKD-MBD) indicates a systemic disorder characterized by abnormal levels of calcium, phosphate, PTH and FGF-23, along with vitamin D deficiency, decreased bone mineral density or altered bone turnover and vascular calcification. A growing body of evidence shows that CKD patients can be affected by subclinical vitamin K deficiency; this has led to identifying such a condition as a potential therapeutic target given the specific role of Vitamin K in metabolism of several proteins involved in bone and vascular health. In other words, we can hypothesize that vitamin K deficiency is the common pathogenetic link between impaired bone mineralization and vascular calcification. However, some of the most common approaches to CKD, such as (1) low vitamin K intake due to nutritional restrictions, (2) warfarin treatment, (3) VDRA and calcimimetics, and (4) phosphate binders, may instead have the opposite effects on vitamin K metabolism and storage in CKD patients.

Topics: Calcium; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Hyperparathyroidism; Osteocalcin; Phosphates; Renal Insufficiency, Chronic; Risk Factors; Vascular Calcification; Vitamin K; Vitamin K Deficiency; Warfarin

Malabsorption and deficiency of fat-soluble vitamins K may occur in cystic fibrosis, a genetic disorder affecting multiple organs. Vitamin K is known to play an important role in both blood coagulation and bone formation, hence the role of supplementation of vitamin K in this category needs to be reviewed. This is an updated version of the review.. To assess the effects of vitamin K supplementation in people with cystic fibrosis and to investigate the hypotheses that vitamin K will decrease deficiency-related coagulopathy, increase bone mineral density, decrease risk of fractures and improve quality of life in people with CF. Also to determine the optimal dose and route of administration of vitamin K for people with CF (for both routine and therapeutic use).. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 12 August 2019.. Randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in patients with cystic fibrosis.. Two authors independently screened papers, extracted trial details and assessed their risk of bias. The quality of the evidence was assessed using the GRADE criteria.. Three trials (total 70 participants, aged 8 to 46 years) assessed as having a moderate risk of bias were included. One trial compared vitamin K to placebo, a second to no supplementation and the third compared two doses of vitamin K. No trial in either comparison reported our primary outcomes of coagulation and quality of life or the secondary outcomes of nutritional parameters and adverse events. Vitamin K versus control Two trials compared vitamin K to control, but data were not available for analysis. One 12-month trial (n = 38) compared 10 mg vitamin K daily or placebo in a parallel design and one trial (n = 18) was of cross-over design with no washout period and compared 5 mg vitamin K/week for four-weeks to no supplementation for four-weeks. Only the 12-month trial reported on the primary outcome of bone formation; we are very uncertain whether vitamin K supplementation has any effect on bone mineral density at the femoral hip or lumbar spine (very low-quality evidence). Both trials reported an increase in serum vitamin K levels and a decrease in undercarboxylated osteocalcin levels. The cross-over trial also reported that levels of proteins induced by vitamin K absence (PIVKA) showed a decrease and a return to normal following supplementation, but due to the very low-quality evidence we are not certain that this is due to the intervention. High-dose versus low-dose vitamin K One parallel trial (n = 14) compared 1 mg vitamin K/day to 5 mg vitamin K/day for four weeks. The trial did report that there did not appear to be any difference in serum undercarboxylated osteocalcin or vitamin K levels (very low-quality evidence). While the trial reported that serum vitamin K levels improved with supplementation, there was no difference between the high-dose and low-dose groups.. There is very low-quality evidence of any effect of vitamin K in people with cystic fibrosis. While there is no evidence of harm, until better evidence is available the ongoing recommendations by national CF guidelines should be followed.

Topics: Adolescent; Adult; Biomarkers; Blood Coagulation; Bone Density; Child; Cystic Fibrosis; Dietary Supplements; Fractures, Bone; Humans; Middle Aged; Osteocalcin; Osteogenesis; Protein Precursors; Prothrombin; Quality of Life; Randomized Controlled Trials as Topic; Vitamin K; Vitamin K Deficiency; Vitamins

Vitamin K is essential for blood coagulation and plays an important role in extrahepatic metabolism, such as in bone and blood vessels, and in energy metabolism. This review discusses the assessment of vitamin K sufficiency and the role of vitamin K in bone health. To elucidate the exact role of vitamin K in other organs, accurate tools for assessing vitamin K deficiency or insufficiency are crucial. Undercarboxylated vitamin K-dependent protein levels can be measured to evaluate tissue-specific vitamin K deficiency/insufficiency. Vitamin K has genomic action through steroid and xenobiotic receptor (SXR); however, the importance of this action requires further study. Recent studies have revealed that the bone-specific, vitamin K-dependent protein osteocalcin has a close relationship with energy metabolism through insulin sensitivity. Among the organs that produce vitamin K-dependent proteins, bone has attracted the most attention, as vitamin K deficiency has been consistently associated with bone fractures. Although vitamin K treatment addresses vitamin K deficiency and is believed to promote bone health, the corresponding findings on fracture risk reduction are conflicting. We also discuss the similarity of other vitamin supplementations on fracture risk. Future clinical studies are needed to further elucidate the effect of vitamin K on fracture risk.

Topics: Adult; Aged; Aged, 80 and over; Bone and Bones; Bone Density; Female; Fractures, Bone; Humans; Male; Middle Aged; Osteocalcin; Vitamin K; Vitamin K Deficiency; Young Adult

Vascular calcification is a known complication of chronic kidney disease (CKD). The prevalence of vascular calcification in patients with non-dialysis-dependent CKD stages 3-5 has been shown to be as high as 79% (20). Vascular calcification has been associated with increased risk for mortality, hospital admissions, and cardiovascular disease (6, 20, 50, 55). Alterations in mineral and bone metabolism play a pivotal role in the pathogenesis of vascular calcification in CKD. As CKD progresses, levels of fibroblast growth factor-23, parathyroid hormone, and serum phosphorus increase and levels of 1,25-(OH)

Topics: Animals; Anticoagulants; Arteries; Dietary Supplements; Humans; Iatrogenic Disease; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Signal Transduction; Vascular Calcification; Vitamin K; Vitamin K Deficiency; Warfarin

Vitamin K acts as a coenzyme of carboxylase, catalyzing the carboxylation of several vitamin K dependent proteins. Beyond its well-known effects on blood coagulation, it also exerts relevant effects on bone and the vascular system. In this review, we point out the relevance of an adequate vitamin K intake to obtain sufficient levels of carboxylated (active form) vitamin K dependent proteins (such as Osteocalcin and matrix Gla protein) to prevent bone health. Another bone-related action of Vitamin K is being a ligand of the nuclear steroid and xenobiotic receptor (SXR). We also discuss the recommended intake, deficiency, and assessment of vitamin K. Furthermore, we review the few available studies that have as pre-specified outcome bone fractures, indicating that we need more clinical studies to confirm that vitamin K is a potential therapeutic agent for bone fractures.

Topics: Fractures, Bone; Humans; Osteoporosis; Pregnane X Receptor; Vitamin K; Vitamin K Deficiency

The cardinal biological role of vitamin K is to act as cofactor for the carboxylation of a number of vitamin K-dependent proteins, some of which are essential for coagulation, bone formation and prevention of vascular calcification. Functional vitamin K deficiency is common and severe among dialysis patients and has garnered attention as a modifiable risk factor in this population. However, no single biochemical parameter can adequately assess vitamin K status. For each biological function of vitamin K, the degree of carboxylation of the relevant vitamin K-dependent protein most accurately reflects vitamin K status. Dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP) is the best biomarker for vascular vitamin K status when cardiovascular endpoints are studied. Dp-ucMGP levels are severely elevated in haemodialysis patients and correlate with markers of vascular calcification and mortality in some but not all studies. The aetiology of vitamin K deficiency in haemodialysis is multifactorial, including deficient intake, uraemic inhibition of the vitamin K cycle and possibly interference of vitamin K absorption by phosphate binders. The optimal vitamin K species, dose and duration of supplementation to correct vitamin K status in dialysis patients are unknown. Dp-ucMGP levels dose-proportionally decrease with supraphysiological vitamin K2 supplementation, but do not normalize even with the highest doses. In the general population, long-term vitamin K1 or K2 supplementation has beneficial effects on cardiovascular disease, bone density and fracture risk, and insulin resistance, although some studies reported negative results. In haemodialysis patients, several trials on the effects of vitamin K on surrogate markers of vascular calcification are currently ongoing.

Topics: Biomarkers; Dietary Supplements; Humans; Longitudinal Studies; Renal Dialysis; Risk Factors; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency; Vitamins

Vascular calcification (VC) is common in advanced chronic kidney disease (CKD), contributes to cardiovascular disease (CVD), and associates with increased mortality. Major risk factors for VC in CKD are increasing age, dialysis vintage, and positive net calcium-phosphate balance. To date, no specific therapy that prevents progression or facilitates regression of VC beyond careful attention to calcium and phosphate balance exists. Accumulating evidence demonstrates that CKD patients may incur subclinical vitamin K deficiency. This deficiency may be induced by exhaustion of vitamin K due to its high requirement by vitamin K-dependent proteins to inhibit VC. This review analyzes the pathophysiological mechanisms and clinical consequences of vitamin K deficiency with emphasis on its involvement on vascular calcification in CKD and end-stage renal disease and its relationship to the bone-vascular axis.

Topics: Humans; Kidney Failure, Chronic; Uremia; Vascular Calcification; Vitamin K; Vitamin K Deficiency

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Cardiovascular Diseases; Female; Humans; Male; Middle Aged; Prognosis; Risk Assessment; Risk Factors; Vitamin K; Vitamin K Deficiency

Vascular calcification is a critical complication in patients with chronic kidney disease (CKD) because it is predictive of cardiovascular events and mortality. In addition to the traditional mechanisms associated with endothelial dysfunction and the osteoblastic transformation of vascular smooth muscle cells (VSMCs), the regulation of calcification inhibitors, such as calciprotein particles (CPPs) and matrix vesicles plays a vital role in uremic vascular calcification in CKD patients because of the high prevalence of vitamin K deficiency. Vitamin K governs the gamma-carboxylation of matrix Gla protein (MGP) for inhibiting vascular calcification, and the vitamin D binding protein receptor is related to vitamin K gene expression. For patients with chronic kidney disease, adequate use of vitamin D supplements may play a role in vascular calcification through modulation of the calciprotein particles and matrix vesicles (MVs).

Topics: Calcium-Binding Proteins; Dietary Supplements; Extracellular Matrix Proteins; Humans; Hyperphosphatemia; Matrix Gla Protein; Myocytes, Smooth Muscle; Renal Insufficiency, Chronic; Vascular Calcification; Vitamin D; Vitamin D Deficiency; Vitamin K; Vitamin K Deficiency

Vitamin K is a composite term referring to a group of fat-soluble vitamins that function as a cofactor for the enzyme γ-glutamyl carboxylase (GGCX), which activates a number of vitamin K-dependent proteins (VKDPs) involved in haemostasis and vascular and bone health. Accumulating evidence demonstrates that chronic kidney disease (CKD) patients suffer from subclinical vitamin K deficiency, suggesting that this represents a population at risk for the biological consequences of poor vitamin K status. This deficiency might be caused by exhaustion of vitamin K due to its high requirements by vitamin K-dependent proteins to inhibit calcification.

Topics: Bone and Bones; Carbon-Carbon Ligases; Dietary Supplements; Humans; Nutritional Status; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Vitamin K; Vitamin K Deficiency; Warfarin

Matrix Gla Protein (MGP), a small Gla vitamin K-dependent protein, is the most powerful natural occurring inhibitor of calcification in the human body. To become biologically active, MGP must undergo vitamin K-dependent carboxylation and phosphorylation. Vitamin K deficiency leads to the inactive uncarboxylated, dephosphorylated form of MGP (dpucMGP). We aimed to review the existing data on the association between circulating dpucMGP and vascular calcification, renal function, mortality, and cardiovascular disease in distinct populations. Moreover, the association between vitamin K supplementation and serum levels of dpucMGP was also reviewed.

Topics: Biological Transport; Calcium-Binding Proteins; Cardiovascular Diseases; Dietary Supplements; Extracellular Matrix Proteins; Gene Expression Regulation; Humans; Matrix Gla Protein; Phosphorylation; Protein Processing, Post-Translational; Renal Insufficiency, Chronic; Survival Analysis; Vascular Calcification; Vascular Stiffness; Vitamin K; Vitamin K Deficiency

Patients receiving vitamin K antagonists (VKAs) with an international normalized ratio (INR) between 4.5 and 10 are at increased risk of bleeding. We systematically reviewed the literature to evaluate the effectiveness and safety of administering vitamin K in patients receiving VKA therapy with INR between 4.5 and 10 and without bleeding. Medline, Embase, and Cochrane databases were searched for relevant randomized controlled trials in April 2018. Search strategy included terms vitamin K administration and VKA-related terms. Reference lists of relevant studies were reviewed, and experts in the field were contacted for relevant papers. Two investigators independently screened and collected data. Risk ratios (RRs) were calculated, and certainty of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. Six studies (1074 participants) were included in the review and meta-analyses. Pooled estimates indicate a nonsignificant increased risk of mortality (RR = 1.42; 95% confidence interval [CI], 0.62-2.47), bleeding (RR = 2.24; 95% CI, 0.81-7.27), and thromboembolism (RR = 1.29; 95% CI, 0.35-4.78) for vitamin K administration, with moderate certainty of the evidence resulting from serious imprecision as CIs included potential for benefit and harm. Patients receiving vitamin K had a nonsignificant increase in the likelihood of reaching goal INR (1.95; 95% CI, 0.88-4.33), with very low certainty of the evidence resulting from serious risk of bias, inconsistency, and imprecision. Our findings indicate that patients on VKA therapy who have an INR between 4.5 and 10.0 without bleeding are not likely to benefit from vitamin K administration in addition to temporary VKA cessation.

Topics: Anticoagulants; Hemorrhage; Humans; International Normalized Ratio; Risk Assessment; Vitamin K; Vitamin K Deficiency

Currently, 1-2% of the population in developed countries are under treatment with oral anticoagulants. An appropriate strategy to deal with this increase in demand of treatment with oral anticoagulants and to manage the costs is the transfer of part or all of the responsibility for managing treatment to the patients. The use of information technology, particularly electronic health software, can be an appropriate method to improve the quality of self-management of treatment with these drugs. Therefore, this systematic review investigated studies that discuss the characteristics of electronic health software in self-management of oral anticoagulation therapy.. A systematic review based on PRISMA protocol was conducted. In this study, articles were investigated that were in English. Articles existing in Cochrane, EMBASE and PubMed databases were searched up to 14 May 2017. Then, articles searched through Google Scholar were added to this study.. The common characteristics used in most software included 'encryption in exchanging information', having an 'instruction module' and 'being Android-based'. In terms of functionality, 'communication between the patient and healthcare team' existed in most of the software.. The results of the study showed that the accuracy of administration of the dose of the drug using computer to reach a target international normalized ratio level was not less than those administered with experienced medical staff. In addition, the results indicated that important characteristics of the software include encryption in exchanging information, instruction module and Android-based instruction module. The most important characteristic was the interaction between the patient and the healthcare team.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Disease Management; Female; Humans; International Normalized Ratio; Male; Middle Aged; Self-Management; Software; Therapy, Computer-Assisted; Vitamin K; Vitamin K Deficiency

To provide information on the pathogenesis, clinical features, diagnosis, and treatment of calciphylaxis.. This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care.. After participating in this educational activity, the participant should be better able to:1. Recognize the pathogenesis and clinical features of and risk factors for calciphylaxis.2. Explain the diagnosis and management of a patient with calciphylaxis.. Calciphylaxis is a cutaneous ischemic infarct caused by total occlusion of blood vessels initiated by vascular calcification. Until recently, treatments have been limited to controlling its risk factors and optimizing wound care. However, recent advances in clinical understanding of the mechanism of calciphylaxis have identified promising potential therapeutic targets. This article is a narrative review summarizing the clinical features, diagnosis, pathogenesis, and treatment of calciphylaxis.

Topics: Calciphylaxis; Chelating Agents; Humans; Kidney Failure, Chronic; Kidney Transplantation; Pain Management; Renal Dialysis; Risk Factors; Thiosulfates; Thrombosis; Vascular Calcification; Vitamin K; Vitamin K Deficiency; Wound Healing

Cystic fibrosis (CF) is an inherited genetic disorder with multiorgan involvement. Gastrointestinal tract dysfunction leads to fat and fat-soluble vitamins (A,D,E,K) malabsorption and deficiency of these vitamins. Subclinical vitamin K (VK) deficiency seems to be a common problem in CF patients. However, despite the rest of fat-soluble vitamins being routinely supplemented, this is not a universal clinical practice for VK. Inefficient levels of VK may have significant effects on blood coagulation and bone formation. There are also some data indicating that VK may play a key role on regulation of inflammation. Supplementing CF patients with VK seems rational, but the appropriate dosing regimens are still a matter of debate. This review will try to delineate the problem and communicate the latest opinions on this controversial issue.

Topics: Blood Coagulation; Cystic Fibrosis; Humans; Osteogenesis; Vitamin K; Vitamin K Deficiency

Vitamin K, a fat-soluble vitamin, is involved in blood coagulation, bone mineralization, inhibition of vascular calcification, and regulation of numerous enzyme systems. Patients who undergo bariatric surgery (BS), especially procedures that involve a malabsorptive component, are prone to develop vitamin K deficiency (VKD). The causes of VKD include decreased absorptive surface areas, steatorrhea, bacterial overgrowth, marked reduction of carriers of vitamin K, decrease in vitamin K intake, and modifications of gut microbiota. Data on vitamin K status among BS patients are scarce and the strength of evidence supporting vitamin K supplementation is weak. Thus, this systematic review summarized the scientific literature on vitamin K and examined the status among patients before and after BS, as well as among pregnant women with a history of BS. A MEDLINE/Pubmed and Embase electronic search was performed. After a thorough screening of 204 titles, 19 articles were selected by 2 independent reviewers. Five studies on BS candidates (n = 750), 12 studies after BS (n = 1442), and 4 studies on pregnant woman after BS (n = 83, of them n = 7 from case reports) were included. Results of the current review suggest that patients who undergo major malabsorptive surgeries are at a higher risk of developing VKD and should be better monitored. At this point, it is still unclear whether supplementation of vitamin K is required, and what oral dose or vitamer type should be used to normalize serum levels after different types of bariatric procedures. It should be noted that the current protocols for VKD treatment are still experiential in these patients. It is also unknown at what intervals screening tests for vitamin K should be performed and what assay is most appropriate for screening purposes. Future studies are needed to answer these unresolved issues.

Topics: Adult; Aged; Bariatric Surgery; Female; Humans; Malabsorption Syndromes; Male; Middle Aged; Obesity, Morbid; Postoperative Complications; Pregnancy; Vitamin K; Vitamin K Deficiency; Young Adult

Fibrosing interstitial pneumonias are associated with various stages of fibrosis. The cause of this group of syndromes remains largely unknown. For most of these diseases, a genetic basis, environmental factors and certain triggers have been suggested as possible risk factors. Various studies have found an association between genetic polymorphisms, or the presence of certain variant alleles, and the occurrence and/or progression of interstitial pneumonias of unknown origin. An acute exacerbation of idiopathic pulmonary fibrosis shows characteristics of diffuse alveolar haemorrhage (DAH). DAH can be aggravated by vitamin K deficiency. This review deals with pharmacogenetic factors underlying interindividual differences of vitamin K status in patients with interstitial pneumonias and the possibilities for a personalized approach to patient management.. DAH has been associated with the presence of variant alleles in vitamin K epoxide reductase complex 1, cytochrome P450 (CYP)2C9 and CYP2C19 genes. Vitamin K deficiency has been associated with an increased risk for the development of DAH and progression and/or deterioration of interstitial pneumonias. This is in line with plausible pathophysiological mechanisms. However, clinical use should be confirmed.. DAH has been associated with vitamin K deficiency and suggested as potential trigger of fibrosing interstitial pneumonias. Information on genetic variation might benefit ongoing/new clinical trials, design of which should reflect needs to address relevance of testing gene variants. Whether vitamin K supplementation may prevent exacerbations or progression of interstitial pneumonias needs to be explored in future studies.

Topics: Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C9; Disease Progression; Hemorrhage; Humans; Idiopathic Pulmonary Fibrosis; Pharmacogenomic Variants; Pulmonary Alveoli; Risk Factors; Vitamin K; Vitamin K Deficiency; Vitamin K Epoxide Reductases

Vitamin K, a fat soluble vitamin, is a necessary cofactor for the activation of coagulation factors II, VII, IX, X, and protein C and S. In neonatal period, vitamin K deficiency may lead to Vitamin K Deficiency Bleeding (VKDB).. We present the case of a 2 months and 20 days Caucasian male, presented for bleeding from the injections sites of vaccines. At birth oral vitamin K prophylaxis was administered. Neonatal period was normal. He was exclusively breastfed and received a daily oral supplementation with 25 μg of vitamin K. A late onset vitamin K deficiency bleeding was suspected. Intravenous Vitamin K was administered with complete recovery.. Nevertheless the oral prophylaxis, our case developed a VKDB: it is necessary to revise the current guidelines in order to standardize timing and dosage in different clinical conditions.

Topics: Administration, Oral; Antifibrinolytic Agents; Hemorrhage; Humans; Infant; Male; Practice Guidelines as Topic; Vitamin K; Vitamin K Deficiency

Topics: Animals; Cardiovascular Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney; Metabolome; Proteins; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Vitamin K; Vitamin K Deficiency

Cystic fibrosis is a genetic disorder which can lead to multiorgan dysfunction. Malabsorption of fat and fat-soluble vitamins (A, D, E, K) may occur and can cause subclinical deficiencies of some of these vitamins. Vitamin K is known to play an important role in both blood coagulation and bone formation. Supplementation with vitamin K appears to be one way of addressing the deficiency, but there is very limited agreement on the appropriate dose and frequency of use of these supplements. This is an updated version of the review.. To assess the effects of vitamin K supplementation in people with cystic fibrosis and to determine the optimal dose and route of administration of vitamin K for both routine and therapeutic use.. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 30 January 2017.. Randomised and quasi-randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in children or adults diagnosed with cystic fibrosis (by sweat test or genetic testing).. Two authors independently screened papers, extracted trial details and assessed their risk of bias.. Two trials (total of 32 participants) each lasting one month were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial in children (aged 8 to 18 years); and the other (with an older cohort) had a cross-over design comparing supplements to no treatment, but no separate data were reported for the first intervention period. Neither of the trials addressed any of the primary outcomes (coagulation, bone formation and quality of life). Both trials reported the restoration of serum vitamin K and undercarboxylated osteocalcin levels to the normal range after one month of daily supplementation with 1 mg of vitamin K.. Evidence from randomised controlled trials on the benefits of routine vitamin K supplementation for people with CF is currently weak and limited to two small trials of short duration. However, no harm was found and until further evidence is available, the present recommendations should be adhered to.

Topics: Adolescent; Adult; Blood Coagulation; Child; Cystic Fibrosis; Dietary Supplements; Humans; Osteogenesis; Quality of Life; Randomized Controlled Trials as Topic; Vitamin K; Vitamin K Deficiency; Vitamins

Subclinical vitamin K deficits refer to carboxylation defects of different types of vitamin K-dependent hepatic and extrahepatic so-called Gla proteins without prolongation of the prothrombin time. This condition has been reported in different clinical situations due to insufficient supply or malabsorption of vitamin K as well as drug interactions. This review discusses the effects of different vitamin K subspecies on tumour growth and the possible anti-tumour effects of increased vitamin K intake. Blocking carboxylation of vitamin K-dependent proteins with warfarin anticoagulation - what are the risks/benefits for carcinogenesis? Previous studies on both heparin and low molecular weight heparin blocking of the vitamin K-dependent factors X and II have shown tumour suppressive effects. Vitamin K has anti-inflammatory effects that could also impact carcinogenesis, but little data exists on this subject.

Topics: Animals; Carcinogenesis; Cell Proliferation; Humans; Neoplasms; Risk Factors; Vitamin K; Vitamin K Deficiency

Cardiovascular diseases are prevalent in patients with chronic obstructive pulmonary disease (COPD). Their coexistence implies that many COPD patients require anticoagulation therapy. Although more and more replaced by direct oral anticoagulants, vitamin K antagonists (VKAs) are still widely used. VKAs induce profound deficiency of vitamin K, a key activator in the coagulation pathway. It is recognized however that vitamin K is also an essential cofactor in the activation of other extrahepatic proteins, such as matrix Gla protein (MGP), a potent inhibitor of arterial calcification. No or insufficient MGP activation by the use of VKAs is associated with a rapid progression of vascular calcification, which may enhance the risk for overt cardiovascular disease. Vitamin K consumption, on the other hand, seems to have a protective effect on the mineralization of arteries. Furthermore, vascular calcification mutually relates to elastin degradation, which is accelerated in patients with COPD associating with impaired survival. In this commentary, we hypothesize that vitamin K is a critical determinant to the rate of elastin degradation. We speculate on the potential link between poor vitamin K status and crucial mechanisms of COPD pathogenesis and raise concerns about the use of VKAs in patients with this disease. Future intervention studies are needed to explore if vitamin K supplementation is able to reduce elastin degradation and vascular calcification in COPD patients.

Topics: Animals; Cardiovascular Diseases; Dietary Supplements; Humans; Pulmonary Disease, Chronic Obstructive; Vascular Calcification; Vitamin K; Vitamin K Deficiency

With the discovery that vitamin K-dependent matrix Gla-protein (MGP) is a strong and modifiable factor in the prevention of arterial calcification, vitamin K was put forward as novel treatment option in cardiovascular disease. The vasculoprotective properties of vitamin K are in part based on the ability to improve gamma-glutamylcarboxylation of MGP, which is a prerequisite for MGP as a calcification inhibitor. Data from experimental animal models reveal that high intake of vitamin K can prevent and even reverse vascular calcifications. In addition, clinical data demonstrate that prescription of vitamin K antagonists for long-term oral anticoagulant therapy accelerates vascular calcification. However, controlled data from randomized prospective vitamin K interventional trials are lacking, thereby weakening a general recommendation for supplementation. The present article summarizes our current knowledge on the association between vitamin K and cardiovascular health. Additionally, we focus on an outlook on important ongoing prospective vitamin K intervention studies. These studies address the issues whether vitamin K substitution helps modifying relevant cardiovascular surrogates such as vascular calcification and whether non-vitamin K oral anticoagulants provide an alternative to support cardiovascular health benefits. So research about cardiovascular protection by vitamin K is an evolving field in which we expect a boost of novel and relevant evidence shortly.

Topics: Animals; Anticoagulants; Atherosclerosis; Dietary Supplements; Humans; Osteocalcin; Protective Factors; Risk Assessment; Risk Factors; Treatment Outcome; Vascular Calcification; Vascular Diseases; Vitamin K; Vitamin K Deficiency

Cystic fibrosis is a genetic disorder which can lead to multiorgan dysfunction. Malabsorption of fat and fat-soluble vitamins (A, D, E, K) may occur and can cause subclinical deficiencies of some of these vitamins. Vitamin K is known to play an important role in both blood coagulation and bone formation. Supplementation with vitamin K appears to be one way of addressing the deficiency, but there is very limited agreement on the appropriate dose and frequency of use of these supplements.. To assess the effects of vitamin K supplementation in people with cystic fibrosis and to determine the optimal dose and route of administration of vitamin K for both routine and therapeutic use.. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 08 October 2014.. Randomised and quasi-randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in children or adults diagnosed with cystic fibrosis (by sweat test or genetic testing).. Two authors independently screened papers, extracted trial details and assessed their risk of bias.. Two trials (total of 32 participants) each lasting one month were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial in children (aged 8 to 18 years); and the other (with an older cohort) had a cross-over design comparing supplements to no treatment, but no separate data were reported for the first intervention period. Neither of the trials addressed any of the primary outcomes (coagulation, bone formation and quality of life). Both trials reported the restoration of serum vitamin K and undercarboxylated osteocalcin levels to the normal range after one month of daily supplementation with 1 mg of vitamin K.. Evidence from randomised controlled trials on the benefits of routine vitamin K supplementation for people with CF is currently weak and limited to two small trials of short duration. However, no harm was found and until further evidence is available, the present recommendations should be adhered to.

Topics: Adolescent; Adult; Blood Coagulation; Child; Cystic Fibrosis; Dietary Supplements; Humans; Osteogenesis; Quality of Life; Randomized Controlled Trials as Topic; Vitamin K; Vitamin K Deficiency; Vitamins

Vitamins D and K are essential for maintaining bone and its deficiency has been associated with several chronic diseases.. To know the intake of vitamins D and K in female population and analyze their involvement on health.. Literature research regarding the topic.. Intake of vitamin D in the Spanish female population from 17 to 60 years is lower than the estimated average requirement in the 95.5% of the studied participants and 30.2% of the Spanish population does not meet the established adequate intake for vitamin K. Several studies have emphasized the importance of maintaining optimal nutrition status of vitamin D for its role in the maintenance of bone, but also for its involvement in body weight control and prevention of diseases (cardiovascular disease, type 2 diabetes, cancer). Vitamin K deficiency is also associated with decreased bone density and increased cardiovascular risk besides exerting a protective effect against type 2 diabetes.. In female population, the intake of vitamin K, but especially vitamin D, is often lower than recommended. Since a worse nutritional status in these vitamins is associated with damage in bone health, weight control, as well as an increased risk of several diseases, it seems appropriate to monitor and improve their intake.. Introducción: las vitaminas D y K juegan un papel esencial en el mantenimiento del hueso, y su deficiencia se ha asociado con diversas enfermedades crónicas. Objetivos: conocer la ingesta de vitaminas D y K en la población femenina y analizar la implicación de su deficiencia en la salud. Métodos: búsqueda bibliográfica en relación con el tema. Resultados: la ingesta de vitamina D en la población femenina española de 17 a 60 años es inferior al EAR en un 96,5% de las mujeres, y un 30,2% de la población española no cubre las IA de vitamina K. Diversos estudios han puesto de relieve la importancia de mantener una situación nutricional de vitamina D óptima, por su papel en el mantenimiento del hueso, pero también por su participación en el control de peso corporal y en la prevención de enfermedades (cardiovasculares, diabetes tipo 2, cáncer, etc.). El déficit de vitamina K también se asocia con una menor densidad ósea y un aumento del riesgo cardiovascular, además de ejercer un efecto protector frente a la diabetes tipo 2. Conclusiones: en el colectivo femenino, la ingesta de vitamina K, pero especialmente la de vitamina D es, con frecuencia, inferior a la recomendada. Dado que una peor situación nutricional en estas vitaminas se asocia con perjuicios en la salud ósea y en el control de peso, así como con un mayor riesgo de padecer diversas enfermedades, parece conveniente vigilar y mejorar el aporte dietético.

Topics: Bone Density; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dietary Supplements; Female; Health Status; Humans; Nutritional Requirements; Nutritional Status; Spain; Vitamin D; Vitamin D Deficiency; Vitamin K; Vitamin K Deficiency; Women's Health

Vitamin K is routinely administered after birth in the UK to prevent haemorrhagic disease of the newborn. Despite this, vitamin K-deficient coagulopathy still occurs in infants with high morbidity and mortality. Up to 50% of late onset bleeding presents with intracranial haemorrhage. The risk of developing vitamin K coagulopathy is higher in infants with cystic fibrosis (CF) and those that are exclusively breast fed due to low vitamin K levels in breast milk and intestinal changes in bacterial flora. Oral vitamin K supplementation is a simple addition to routine CF treatment during infancy to prevent complications from significant coagulopathy.

Topics: Administration, Oral; Cystic Fibrosis; Humans; Infant; Infant, Newborn; Intracranial Hemorrhages; Male; Tomography, X-Ray Computed; Vitamin K; Vitamin K Deficiency; Vitamins

Vitamin K is one of several nutrients that have been linked with bone health. In particular, there is an emerging literature regarding the questionable efficacy of vitamin K supplementation in reducing age-related bone loss. This review aims to summarize the role of vitamin K in bone health in older adults and discuss the clinical implications from a select few human studies. The evidence for vitamin K supplementation in older adults is mixed. Although the observational studies have shown linkages between vitamin K intake and lower risk of fractures in this population, the current evidence from randomized controlled trials is not strongly supportive of vitamin K supplementation in older adults for the intent of improving bone health.

Topics: Aging; Bone and Bones; Diet; Dietary Supplements; Evidence-Based Medicine; Health Promotion; Humans; Nutrition Policy; Osteoporosis; Reproducibility of Results; Vitamin K; Vitamin K Deficiency

In the past few decades vitamin K has emerged from a single-function "haemostasis vitamin" to a "multi-function vitamin." The use of vitamin K antagonists (VKA) inevitably showed that the inhibition was not restricted to vitamin K dependent coagulation factors but also synthesis of functional extrahepatic vitamin K dependent proteins (VKDPs), thereby eliciting undesired side effects. Vascular calcification is one of the recently revealed detrimental effects of VKA. The discovery that VKDPs are involved in vascular calcification has propelled our mechanistic understanding of this process and has opened novel avenues for diagnosis and treatment. This review addresses mechanisms of VKDPs and their significance for physiological and pathological calcification.

Topics: Animals; Anticoagulants; Biomedical Research; Blood Coagulation; Calcification, Physiologic; Calcinosis; Humans; Models, Biological; Vitamin K; Vitamin K Deficiency

Aside from its important role in blood clotting, vitamin K is an important dietary factor in regulating bone and cartilage mineralization. The vitamin K requirements to maintain musculoskeletal health may be more than the current recommendations and subclinical vitamin K deficiency may be involved in the pathogenesis of osteoporosis and osteoarthritis. Observational studies suggest that diets low in vitamin K are associated with increased risk of fractures and osteoarthritis in older adults. However, so far randomized controlled trials of vitamin K supplementation in Caucasian populations have not shown clinically significant improvements in bone mineral density at major skeletal sites. Supplementation with vitamin K may reduce the risk of fractures, but this conclusion comes from clinical trials with methodological limitations. At this time, only one randomized controlled trial has examined the effect of vitamin K supplementation on radiographic hand osteoarthritis and found no overall effect. Large well-designed randomized controlled trials are needed to compare the efficacies of vitamin K1 and K2 on fractures and osteoarthritis among older adults. In summary, currently there is not enough evidence to recommend the use of vitamin K supplements for the prevention of bone loss, fractures, or osteoarthritis in postmenopausal women.

Topics: Aging; Animals; Female; Health Status; Humans; Musculoskeletal Development; Musculoskeletal Physiological Phenomena; Musculoskeletal System; Osteoarthritis; Osteoporosis, Postmenopausal; Postmenopause; Vitamin K; Vitamin K Deficiency

The mechanisms of vascular calcifications in chronic renal failure are complex. Apart for clotting factors, vitamin K-dependent proteins include matrix Gla protein. Glutamic acid residues in matrix Gla protein are carboxylated by vitamin K-dependent gamma-carboxylase, which enables it to inhibit calcification. The purpose of this review is to discuss available evidence implicating vitamin K as a modifiable risk factor in the pathogenesis of vascular calcification in renal diseases.

Topics: Effect Modifier, Epidemiologic; Humans; Models, Biological; Nutritional Physiological Phenomena; Renal Insufficiency, Chronic; Risk Factors; Vascular Calcification; Vitamin K; Vitamin K Deficiency

Cystic fibrosis is a genetic disorder which can lead to multiorgan dysfunction. Malabsorption of fat and fat-soluble vitamins (A, D, E, K) may occur and can cause subclinical deficiencies of some of these vitamins. Vitamin K is known to play an important role in both blood coagulation and bone formation. Supplementation with vitamin K appears to be one way of addressing the deficiency, but there is very limited agreement on the appropriate dose and frequency of use of these supplements.. To assess the effects of vitamin K supplementation in people with cystic fibrosis and to determine the optimal dose and route of administration of vitamin K for both routine and therapeutic use.. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 11 October 2012.. Randomised and quasi-randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in children or adults diagnosed with cystic fibrosis (by sweat test or genetic testing).. Two authors independently screened papers, extracted trial details and assessed their risk of bias.. Two trials (total of 32 participants) were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial; and the other had a cross-over design, but no separate data were reported for the first intervention period. Neither of the trials addressed any of the primary outcomes (coagulation, bone formation and quality of life). Both trials reported the restoration of serum vitamin K and undercarboxylated osteocalcin levels to the normal range after one month of daily supplementation with 1 mg of vitamin K.. Evidence from randomised controlled trials on the benefits of routine vitamin K supplementation for people with CF is currently weak and limited to two small trials of short duration. However, no harm was found and until further evidence is available, the present recommendations should be adhered to.

Topics: Blood Coagulation; Cystic Fibrosis; Dietary Supplements; Humans; Osteogenesis; Quality of Life; Randomized Controlled Trials as Topic; Vitamin K; Vitamin K Deficiency; Vitamins

Hepatic vitamin K-dependent proteins (e.g., Factors II, VII, IX and X) form part of the clotting cascade. Factor II (FII)/Prothrombin incorporates 10 Glu residues on the N-terminal region that are γ-carboxylated to Gla residues by the action of γ-glutamyl carboxylase to confer biological activity. Vitamin K is also required for the normal function of Matrix Gla Protein (MGP)--one of several non-clotting-related extra-hepatic vitamin K-dependent proteins. MGP is known to have protective action against vascular calcification--indeed it is a powerful tissue-bound inhibitory mechanism and can be found in blood vessel walls. The mature protein is also dependent on activation by γ-glutamyl carboxylase enzyme to convert Glu residues in its amino acid sequence to Gla. This reaction can only take place when the enzyme is activated in the presence of vitamin K. It is of great potential interest to investigate whether subtle deficiencies of vitamin K may, through its effect on the action of MGP, be a contributing factor to vascular calcification in CKD patients, in whom CV disease is greatly accelerated and in whom vascular calcification is not only common, but progresses aggressively, and is something for which as yet there is no clinically applicable remedy.

Topics: Adult; Aged; Biomarkers; Calcinosis; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Protein Precursors; Prothrombin; Renal Insufficiency, Chronic; Vascular Diseases; Vitamin K; Vitamin K Deficiency

Osteocalcin originates from osteoblastic synthesis and is deposited into bone or released into circulation, where it correlates with histological measures of bone formation. The presence of 3 vitamin K-dependent γ carboxyglutamic acid residues is critical for osteocalcin's structure, which appears to regulate the maturation of bone mineral. In humans, the percentage of the circulating osteocalcin that is not γ-carboxylated (percent ucOC) is used as a biomarker of vitamin K status. In contrast, when ucOC is not corrected for total osteocalcin, the interpretation of this measure is confounded by osteoblastic activity, independent of vitamin K. Observational studies using percent ucOC have led to the conclusion that vitamin K insufficiency leads to age-related bone loss. However, clinical trials do not provide overall support for the suggestion that vitamin K supplementation of the general population will reduce bone loss or fracture risk. More recently, results from in vitro and in vivo studies using animal models indicate that ucOC is an active hormone with a positive role in glucose metabolism. By inference, vitamin K, which decreases ucOC, would have a detrimental effect. However, in humans this hypothesis is not supported by the limited data available, nor is it supported by what has been established regarding osteocalcin chemistry. In summary, the specific function of osteocalcin in bone and glucose metabolism has yet to be elucidated.

Topics: Animals; Biomarkers; Bone Remodeling; Glutamic Acid; Humans; Osteocalcin; Vitamin K; Vitamin K Deficiency

Topics: Adult; Blood Coagulation; Female; Humans; Infant, Newborn; Liver; Male; Mutation; Vitamin K; Vitamin K Deficiency

Cystic fibrosis is a genetic disorder which can lead to multiorgan dysfunction. Malabsorption of fat and fat-soluble vitamins (A, D, E, K) may occur and can cause subclinical deficiencies of some of these vitamins. Vitamin K is known to play an important role in both blood coagulation and bone formation. Supplementation with vitamin K appears to be one way of addressing the deficiency, but there is very limited agreement on the appropriate dose and frequency of use of these supplements.. To assess the effects of vitamin K supplementation in people with cystic fibrosis and to determine the optimal dose and route of administration of vitamin K for both routine and therapeutic use.. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 15 April 2010.. Randomised and quasi-randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in children or adults diagnosed with cystic fibrosis (by sweat test or genetic testing).. Two authors independently screened papers, extracted trial details and assessed their risk of bias.. Two trials (total of 32 participants) were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial; and the other had a cross-over design, but no separate data were reported for the first intervention period. Neither of the trials addressed any of the primary outcomes (coagulation, bone formation and quality of life). Both trials reported the restoration of serum vitamin K and undercarboxylated osteocalcin levels to the normal range after one month of daily supplementation with 1 mg of vitamin K.. Evidence from randomised controlled trials on the benefits of routine vitamin K supplementation for people with CF is currently weak and limited to two small trials of short duration. However, no harm was found and until further evidence is available, the present recommendations should be adhered to.

Topics: Blood Coagulation; Cystic Fibrosis; Dietary Supplements; Humans; Osteogenesis; Quality of Life; Randomized Controlled Trials as Topic; Vitamin K; Vitamin K Deficiency; Vitamins

The function of vitamin K is to serve as a co-factor during the post-translational carboxylation of glutamate (Glu) residues into γ-carboxyglutamate (Gla) residues. The vital importance of the Gla-proteins essential for normal haemostasis is well recognized. During recent years, new Gla-containing proteins have been discovered and the vitamin K-dependent carboxylation is also essential for their function. It seems, however, that our dietary vitamin K intake is too low to support the carboxylation of at least some of these Gla-proteins. According to the triage theory, long-term vitamin K inadequacy is an independent, but modifiable risk factor for the development of degenerative diseases of ageing including osteoporosis and atherosclerosis.

Topics: 1-Carboxyglutamic Acid; Bone and Bones; Humans; Neurodegenerative Diseases; Osteoporosis; Vitamin K; Vitamin K Deficiency; Vitamins

Vitamin K is the most common 'drug' administered to babies born in the western world. For many decades vitamin K prophylaxis has been a routine treatment at birth for preterm infants. Despite universal use in preterm infants, very little work has been done to date to refine vitamin K dosage in this population or to assess vitamin K status after prophylaxis. Current regimens of prophylaxis used for preterm infants vary widely in terms of dose, route of administration, and formulation used.

Topics: Chemoprevention; Humans; Infant Formula; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Nutrition Policy; Premature Birth; Vitamin K; Vitamin K Deficiency

Relatively little is known about the vitamin K status and requirements in term and preterm infants, though hemorrhagic disease of the newborn infant continues to be a worldwide problem. This brief review of vitamin K metabolism, vitamin K dependent proteins, and the vitamin K cycle covers some new thoughts about the importance of vitamin K to human health including the preterm infant. A review of perinatal vitamin K metabolism concludes that little vitamin K actually crosses the placenta from mother to infant. The neonatal sources of vitamin K are generally limited to the vitamin K prophylaxis given at the time of birth, dietary sources, and questionable amounts from vitamin K present in the intestinal tract synthesized from bacteria. Preterm infants receive large quantities of vitamin K from prophylaxis, TPN solutions, infant formula and breast milk fortifiers. Thus, vitamin serum concentration in preterm infants is up to one hundred times higher than those found in adults and 10-20 times those found in term formula-fed infants. Though no toxicity has been reported, the elevation of epoxide reductase (VKOR) from the vitamin K cycle found in the serum of preterm infants is worthy of additional study. PIVKA-II (abnormal prothrombin) is not a reliable indicator of vitamin K deficiency in preterm or term infants.

Topics: Adult; Humans; Infant Nutritional Physiological Phenomena; Infant, Newborn; Models, Biological; Vitamin K; Vitamin K Deficiency

Hereditary combined vitamin K-dependent clotting factors deficiency (VKCFD) is a rare congenital bleeding disorder resulting from variably decreased levels of coagulation factors II, VII, IX and X as well as natural anticoagulants protein C, protein S and protein Z. The spectrum of bleeding symptoms ranges from mild to severe with onset in the neonatal period in severe cases. The bleeding symptoms are often life-threatening, occur both spontaneously and in a surgical setting, and usually involve the skin and mucosae. A range of non-haemostatic symptoms are often present, including developmental and skeletal anomalies. VKCFD is an autosomal recessive disorder caused by mutations in the genes of either gamma-glutamyl carboxylase or vitamin K2,3-epoxide reductase complex. These two proteins are necessary for gamma-carboxylation, a post-synthetic modification that allows coagulation proteins to display their proper function. The developmental and skeletal anomalies seen in VKCFD are the result of defective gamma-carboxylation of a number of non-haemostatic proteins. Diagnostic differentiation from other conditions, both congenital and acquired, is mandatory and genotype analysis is needed to confirm the defect. Vitamin K administration is the mainstay of therapy in VKCFD, with plasma supplementation during surgery or severe bleeding episodes. In addition, prothrombin complex concentrates and combination therapy with recombinant activated FVII and vitamin K supplementation may constitute alternative treatment options. The overall prognosis is good and with the availability of several effective therapeutic options, VKCFD has only a small impact on the quality of life of affected patients.

Topics: Blood Coagulation Disorders, Inherited; Blood Coagulation Factors; Blood Proteins; Carbon-Carbon Ligases; Humans; Infant, Newborn; Protein C; Protein S; Recombinant Proteins; Vitamin K; Vitamin K Deficiency

The considerable variability in the warfarin dose-response relationship between individuals, is explained mainly by genetic variation in its major metabolic (CYP2C9) and target (VKORC1) enzymes. Despite the predominance of pharmacogenetics, environmental factors also affect the pharmacokinetics and pharmacodynamics of warfarin, and are often overlooked. Among these factors, dietary and supplemental vitamin K consumption is a controllable contributor to within-, and between-patient variability of warfarin sensitivity. In this commentary we review the current role of vitamin K in warfarin anticoagulation therapy, with emphasis on the following: 1 The effect of dietary and supplemental vitamin K on warfarin anticoagulation, beyond the impact of genetic variability in CYP2C9 and VKORC1. We deal separately with the effects of vitamin K on warfarin dose requirements during the induction of therapy, as opposed to its effect on stability of anticoagulation control during maintenance therapy. 2 The role of vitamin K supplementation in warfarin treated patients with vitamin K deficiency as well as in patients with unstable warfarin anticoagulation, and 3 The role of therapeutic vitamin K in cases of warfarin over-anticoagulation.

Topics: Anticoagulants; Aryl Hydrocarbon Hydroxylases; Blood Coagulation; Cytochrome P-450 CYP2C9; Dietary Supplements; Dose-Response Relationship, Drug; Drug Interactions; Humans; Mixed Function Oxygenases; Mutation; Vitamin K; Vitamin K Deficiency; Vitamin K Epoxide Reductases; Warfarin

Vitamin K is well known for its role in the synthesis of a number of blood coagulation factors. Vitamin K is also an important factor for bone metabolism via gamma-carboxylation of vitamin K-dependent proteins such as osteocalcin, matrix Gla protein, and protein S. Recent studies suggest that there is potential vitamin K insufficiency in bone, even in sufficient vitamin K status for blood coagulation. In the present review, the studies concerning relationship between vitamin K status and fracture are reviewed.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Calcium-Binding Proteins; Extracellular Matrix Proteins; Female; Fractures, Bone; Humans; Male; Matrix Gla Protein; Middle Aged; Osteocalcin; Vitamin K; Vitamin K Deficiency; Young Adult

Vitamins D and K are lipid-phase nutrients that are pleiotropic - endowed with versatile homeostatic capacities at the organ, tissue, and cellular levels. Their metabolic and physiologic roles overlap considerably, as evidenced in the bone and cardiovascular systems. Vitamin D₃ (cholecalciferol, D₃) is the prehormone for the vitamin D endocrine system. Vitamin D₃ undergoes initial enzymatic conversion to 25-hydroxyvitamin D (25D, calcidiol), then to the seco-steroid hormone 1alpha, 25-dihydroxyvitamin D (1,25D, calcitriol). Beyond its endocrine roles in calcium homeostasis, 1,25D likely has autocrine, paracrine, and intracrine effects. At least 17 tissues likely synthesize 1,25D, and 35 carry the vitamin D receptor (VDR). Vitamin D functional deficiency is widespread in human populations. Vitamin K₁ (phylloquinone) is more abundant in foods but less bioactive than the vitamin K₂ menaquinones (especially MK-4, menatetrenone). Menadione (vitamin K₃) has minimal K activity. Vitamin K compounds undergo oxidation-reduction cycling within the endoplasmic reticulum membrane, donating electrons to activate specific proteins via enzymatic gamma-carboxylation of glutamate groups before being enzymatically re-reduced. Warfarin inhibits this vitamin K reduction, necessitating K supplementation during anticoagulation therapy. Along with coagulation factors (II, VII, IX, X, and prothrombin), protein C and protein S, osteocalcin (OC), matrix Gla protein (MGP), periostin, Gas6, and other vitamin K-dependent (VKD) proteins support calcium homeostasis, facilitate bone mineralization, inhibit vessel wall calcification, support endothelial integrity, are involved in cell growth control and tissue renewal, and have numerous other effects. This review updates vitamin D and K skeletal and cardiovascular benefits and evidence for their synergy of action.

Topics: Bone and Bones; Bone Density; Bone Diseases; Calcification, Physiologic; Cardiovascular Diseases; Cardiovascular System; Cholecalciferol; Fractures, Bone; Humans; Nutritional Physiological Phenomena; Osteoblasts; Osteocytes; Vitamin D Deficiency; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K 3; Vitamin K Deficiency

Vitamin K deficiency bleeding (VKDB) is a rare and potentially life-threatening bleeding disorder of early infancy. Vitamin K stores are low at birth; thereafter breast-fed infants are at risk because of low concentrations in human milk. Classical VKDB occurs in the first week of life, is related to delayed or inadequate feeding and is readily prevented by small doses of vitamin K at birth. Late VKDB peaks at 3-8 weeks, typically presents with intracranial haemorrhage often due to undiagnosed cholestasis with resultant malabsorption of vitamin K. Diagnosis can be difficult but PIVKA-II measurements can provide confirmation even several days post-treatment. Without vitamin K prophylaxis, the incidence of late VKDB in Europe is 4-7 cases per 10(5) births; it is higher in SE Asia where in rural, low-income areas some 0.1% of affected infants may suffer intracranial bleeding. Late VKDB is largely preventable with parenteral vitamin K providing the best protection. The efficacy of oral prophylaxis is related to the dose and frequency of administration. Most multi-dose oral regimens provide protection for all except a small reservoir of infants with undetected hepatobiliary disease. Targeted surveillance of high-risk groups (e.g. biliary atresia) offers a novel approach to assess efficacy of prophylaxis.

Topics: Humans; Infant, Newborn; Vitamin K; Vitamin K Deficiency

This review summarizes current knowledge on vitamin K for the paediatrician. Vitamin K is a fat-soluble vitamin, present in plants as phylloquinone and produced by bacteria as menaquinone. It is acting as a co-factor for gamma-glutamyl carboxylase. This enzyme is responsible for post-translational modification of some glutamate side chains to gamma-carboxyglutamate. The majority of gamma-carboxylated proteins function in blood coagulation; others play a role in calcium homeostasis.. Newborn babies are at particular risk of vitamin K deficiency, as placental transfer is limited and human milk is a poor source. Vitamin K prophylaxis at birth effectively prevents vitamin K deficiency bleeding (VKDB), formerly known as "haemorrhagic disease of the newborn". Recent epidemiological studies provide data on the effectiveness of different administration routes and dosing schemes. Infants of mothers taking drugs that inhibit vitamin K are at risk of early VKDB and should receive 1 mg intramuscular (i.m.) as soon as possible after birth. Classic VKDB is prevented by intramuscular as well as by oral administration of 1 mg vitamin K. In exclusively breast-fed infants, single i.m. administration at birth is also effectively preventing (rare) late VKDB but single oral administration is not. If given orally, prophylaxis should be continued by either weekly administration of 1 mg till 12 weeks or repeating 2 mg at weeks 1 and 4. Daily administration of 25 microg offers insufficient protection. The only infants not fully protected in this way are those with yet unrecognised liver disease.. Further work is needed before firm recommendations can be made regarding dose in preterm infants and in patients with fat malabsorption/cholestasis or regarding the role of vitamin K in the prevention of osteoporosis.

Topics: Administration, Oral; Blood Coagulation; Breast Feeding; Calcium; Dose-Response Relationship, Drug; Drug Administration Schedule; Homeostasis; Humans; Infant, Newborn; Infant, Premature, Diseases; Injections, Intramuscular; Liver; Risk Factors; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

All vitamin K-dependent coagulation factors require normal function of gamma-glutamyl carboxylase and vitamin K epoxide reductase enzyme complex (VKORC1). Heritable dysfunction of gamma-glutamyl carboxylase or of the VKORC1 complex results in the secretion of poorly carboxylated vitamin K-dependent proteins that play a role in coagulation. The following review will summarize the clinical manifestations of vitamin K-dependent coagulation factors deficiency I and II and will provide a detailed explanation about the gene and protein structure, the function of the protein, and an analysis of the previously reported mutations. Laboratory assays used for diagnosis will be discussed, and treatment for various clinical settings will be recommended.

Topics: Blood Coagulation Factors; Carbon-Carbon Ligases; Child; Female; Humans; Infant; Infant, Newborn; Mixed Function Oxygenases; Partial Thromboplastin Time; Phenotype; Prenatal Diagnosis; Preoperative Care; Prothrombin Time; Vitamin K; Vitamin K Deficiency; Vitamin K Epoxide Reductases

The triage theory posits that some functions of micronutrients (the approximately 40 essential vitamins, minerals, fatty acids, and amino acids) are restricted during shortage and that functions required for short-term survival take precedence over those that are less essential. Insidious changes accumulate as a consequence of restriction, which increases the risk of diseases of aging. For 16 known vitamin K-dependent (VKD) proteins, we evaluated the relative lethality of 11 known mouse knockout mutants to categorize essentiality. Results indicate that 5 VKD proteins that are required for coagulation had critical functions (knockouts were embryonic lethal), whereas the knockouts of 5 less critical VKD proteins [osteocalcin, matrix Gla protein (Mgp), growth arrest specific protein 6, transforming growth factor beta-inducible protein (Tgfbi or betaig-h3), and periostin] survived at least through weaning. The VKD gamma-carboxylation of the 5 essential VKD proteins in the liver and the 5 nonessential proteins in nonhepatic tissues sets up a dichotomy that takes advantage of the preferential distribution of dietary vitamin K1 to the liver to preserve coagulation function when vitamin K1 is limiting. Genetic loss of less critical VKD proteins, dietary vitamin K inadequacy, human polymorphisms or mutations, and vitamin K deficiency induced by chronic anticoagulant (warfarin/coumadin) therapy are all linked to age-associated conditions: bone fragility after estrogen loss (osteocalcin) and arterial calcification linked to cardiovascular disease (Mgp). There is increased spontaneous cancer in Tgfbi mouse knockouts, and knockdown of Tgfbi causes mitotic spindle abnormalities. A triage perspective reinforces recommendations of some experts that much of the population and warfarin/coumadin patients may not receive sufficient vitamin K for optimal function of VKD proteins that are important to maintain long-term health.

Topics: Aging; Animals; Anticoagulants; Blood Coagulation; Disease; Humans; Liver; Mice; Mice, Knockout; Mutation; Polymorphism, Genetic; Proteins; Vitamin K; Vitamin K Deficiency

Vitamin D and K are nutrients necessary for bone health. Vitamin D insufficiency, which is milder than vitamin D deficiency to cause rickets and osteomalacia, is associated with increased fracture risk. Serum 25 (OH) D concentration, a good marker for vitamin D status, must be higher than the traditional held consensus of 20 ng/mL for bone health. Daily dose of 800 IU or higher is considered to be necessary for fracture prevention. Recently, much attention has been paid on extra-hepatic actions of vitamin K including bone. Elevated serum concentration of undercarboxylated osteocalcin, a sensitive marker for vitamin K inadequacy in the bone, is a risk factor for fracture independent of bone mineral density.

Topics: Biomarkers; Fats; Fractures, Bone; Humans; Osteocalcin; Osteomalacia; Rickets; Risk; Solubility; Vitamin D; Vitamin D Deficiency; Vitamin K; Vitamin K Deficiency

Vitamin K (as phylloquinone and menaquinones) is an essential cofactor for the conversion of peptide-bound glutamate to gamma-carboxy glutamic acid (Gla) residues in a number of specialized Gla-containing proteins. The only unequivocal deficiency outcome is a bleeding syndrome caused by an inability to synthesize active coagulation factors II, VII, IX, and X, although there is growing evidence for roles for vitamin K in bone and vascular health. An adult daily intake of about 100 microg of phylloquinone is recommended for the maintenance of hemostasis. Traditional coagulation tests for assessing vitamin K status are nonspecific and insensitive. Better tests include measurements of circulating vitamin K and inactive proteins such as undercarboxylated forms of factor II and osteocalcin to assess tissue and functional status, respectively. Common risk factors for vitamin K deficiency in the hospitalized patient include inadequate dietary intakes, malabsorption syndromes (especially owing to cholestatic liver disease), antibiotic therapy, and renal insufficiency. Pregnant women and their newborns present a special risk category because of poor placental transport and low concentrations of vitamin K in breast milk. Since 2000, the Food and Drug Administration has mandated that adult parenteral preparations should provide a supplemental amount of 150 microg phylloquinone per day in addition to that present naturally, in variable amounts, in the lipid emulsion. Although this supplemental daily amount is probably beneficial in preventing vitamin K deficiency, it may be excessive for patients taking vitamin K antagonists, such as warfarin, and jeopardize their anticoagulant control. Natural forms of vitamin K have no proven toxicity.

Topics: Adult; Anticoagulants; Antifibrinolytic Agents; Bacteria; Blood Coagulation; Bone and Bones; Colon; Diet; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Health; Hospitalization; Humans; Infant, Newborn; Liver Diseases; Nutritional Requirements; Parenteral Nutrition; Practice Guidelines as Topic; Pregnancy; Vitamin K; Vitamin K Deficiency

Insufficient vitamin K nutrition is one of the risks for bone fracture. Vitamin K is clinically applied to osteoporosis treatment in Japan and Asian countries, as the administration has preventive effects on bone fracture. Recent studies have revealed that vitamin K functions as a ligand for Steroid and Xenobiotic Receptor (SXR), as well as a cofactor for gamma-carboxylase. In osteoblastic cells, several SXR responsive genes have been identified, including tsukushi, matrilin-2, CD14, and Msx2. Working together with gamma-carboxylated bone proteins, these SXR targets will function in the vitamin K-mediated bone protection. It has been also suggested that vitamin K could prevent or treat the hepatocellular carcinoma (HCC) in some clinical studies. SXR may also contribute to the vitamin K-dependent reduction of HCC.

Topics: Carbon-Carbon Ligases; Carcinoma, Hepatocellular; Coenzymes; Fractures, Spontaneous; Humans; Ligands; Liver Neoplasms; Osteoblasts; Osteoporosis; Pregnane X Receptor; Receptors, Steroid; Vitamin K; Vitamin K Deficiency

Coagulation factors do not cross the placental barrier but are synthesized independently by the conceptus. At birth, activities of the vitamin K dependent factors II, VII, IX, and X and the concentrations of the contact factors XI and XII are reduced to about 50% of normal adult values. The levels of the factors V, VIII, XIII, and fibrinogen are similar to adult values. Plasma concentrations of the naturally occurring anticoagulant proteins (antithrombin, protein C, and protein S) are significantly lower at birth than during the adult years. Plasminogen is reduced by approximately 50%. Platelet counts are within the normal range, regarding function, however, neonatal platelets seem to be hyporeactive. The von Willebrand factor contains large multimers and its concentration is increased. Properties and functions of vitamin K as well as requirement and plasma concentrations in newborns are reviewed. Regarding vitamin K deficiency bleeding (VKDB), the classical nomenclature is used: "early" (presenting within the first 24 h of life), "classical" (day 1-7 after birth), and "late" (8 days to 6 months). After the presentation of the history of vitamin K prophylaxis, vitamin K levels are described as can be expected after the administration of prophylactic doses at various routes. Subsequently, the actual schedule of vitamin K prophylaxis as recommended by the "Osterreichische Gesellschaft für Kinder- und Jugendheilkunde" is given as follows: i) the oral treatment of healthy full-term babies and orally fed preterm babies, ii) the parenteral treatment of small preterm and sick full-term babies, and iii) the treatment of mothers under medication with enzyme-inducing drugs with vitamin K during the last 15-30 days of pregnancy. The regimes of prophylactic vitamin K treatment of different countries are also given. Finally, the therapeutic use of vitamin K is addressed; the potential use of fresh-frozen plasma, prothrombin complex preparations, and recombinant factor VIIa is discussed.

Topics: Administration, Oral; Adult; Age Factors; Antithrombins; Austria; Blood Coagulation; Blood Coagulation Factors; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Infusions, Parenteral; Maternal-Fetal Exchange; Practice Guidelines as Topic; Pregnancy; Protein C; Protein S; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding; von Willebrand Factor

A protective role for vitamin K in bone health has been suggested based on its role as an enzymatic cofactor. In observational studies, vitamin K insufficiency is generally associated with lower bone mass and increased hip fracture risk. However, these findings are not supported in randomized controlled trials (RCT) of phylloquinone (vitamin K(1)) supplementation and bone loss at the hip in the elderly. This suggests that increased vegetable and legume intakes may simultaneously improve measures of vitamin K status and skeletal health, even though the mechanisms underlying these improvements may be independent of each other. Menaquinone-4 (vitamin K(2)), when given at pharmacological doses, appears to protect against fracture risk and bone loss at the spine. However, there are emerging data that suggest the efficacy of vitamin K supplementation on bone loss is inconclusive.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bone and Bones; Bone Density; Child; Child, Preschool; Dietary Supplements; Female; Humans; Male; Middle Aged; Osteoporosis; Randomized Controlled Trials as Topic; Vitamin K; Vitamin K 1; Vitamin K Deficiency

Naturally occurring vitamin K compounds comprise a plant form, phylloquinone (vitamin K(1)) and a series of bacterial menaquinones (MKs) (vitamin K(2)). Structural differences in the isoprenoid side chain govern many facets of metabolism of K vitamins including the way they are transported, taken up by target tissues, and subsequently excreted. In the post-prandial state, phylloquinone is transported mainly by triglyceride-rich lipoproteins (TRL) and long-chain MKs mainly by low-density lipoproteins (LDL). TRL-borne phylloquinone uptake by osteoblasts is an apoE-mediated process with the LRP1 receptor playing a predominant role. One K(2) form, MK-4, has a highly specific tissue distribution suggestive of local synthesis from phylloquinone in which menadione is an intermediate. Both phylloquinone and MKs activate the steroid and xenobiotic receptor (SXR) that initiates their catabolism, but MK-4 specifically upregulates two genes suggesting a novel MK-4 signalling pathway. Many studies have shown specific clinical benefits of MK-4 at pharmacological doses for osteoporosis and cancer although the mechanism(s) are poorly understood. Other putative non-cofactor functions of vitamin K include the suppression of inflammation, prevention of brain oxidative damage and a role in sphingolipid synthesis. Anticoagulant drugs block vitamin K recycling and thereby the availability of reduced vitamin K. Under extreme blockade, vitamin K can bypass the inhibition of Gla synthesis in the liver but not in the bone and the vessel wall. In humans, MK-7 has a greater efficacy than phylloquinone in carboxylating both liver and bone Gla proteins. A daily supplement of phylloquinone has shown potential for improving anticoagulation control.

Topics: Animals; Anticoagulants; Blood Proteins; Hepatocytes; Humans; Osteocytes; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

Vitamin K is a nutrient originally identified as an essential factor for blood coagulation. Accumulated evidence indicates that subclinical non-hemostatic vitamin K deficiency in extrahepatic tissues, particularly in bone, exists widely in the otherwise healthy adult population. Both vitamin K1 and K2 have been shown to exert protective effects against osteoporosis. The new biological functions of vitamin K in bone are considered to be attributable, at least in part, to promotion of gamma-carboxylation of glutamic acid residues in vitamin K-dependent proteins, which is shared by both vitamins K1 and K2. A recent evidence of significant correlation between polymorphism of gamma-glutamyl carboxylase gene and bone mineral density supports the role of gamma-carboxylation-dependent actions of vitamin K. In contrast, vitamin K2-specific,gamma-carboxylation-unrelated functions have recently attracted scientific attention. Recent findings of vitamin K2-specific transactivation of steroid and xenobiotic receptor (SXR/PXR) may lead to new research avenue. The impact of genotype of apoE, a major vitamin K transporter, on ostepporosis as well as Alzheimer disease and atherosclerosis, raises a question whether vitamin K is involved in the pathogenesis of these diseases. Molecular bases of coagulation-unrelated pleiotropic actions of vitamin K and its implications in bone health deserve further investigations.

Topics: Adult; Bone and Bones; Humans; Osteoporosis; Vitamin K; Vitamin K Deficiency

Vitamin K, discovered in the 1930s, functions as cofactor for the posttranslational carboxylation of glutamate residues. Gammacarboxy glutamic acid (Gla)-residues were first identified in prothrombin and coagulation factors in the 1970s; subsequently, extra-hepatic Gla proteins were described, including osteocalcin and matrix Gla protein (MGP). Impairment of the function of osteocalcin and MGP due to incomplete carboxylation results in an increased risk for developing osteoporosis and vascular calcification, respectively, and is an unexpected side effect of treatment with oral anticoagulants. It is conceivable that other side effects, possible involving growth-arrest-specific gene 6 (Gas6) protein will be identified in forthcoming years. In healthy individuals, substantial fractions of osteocalcin and MGP circulate as incompletely carboxylated species, indicating that the majority of these individuals is subclinically vitamin K-deficient. Potential new application areas for vitamin K are therefore its use in dietary supplements and functional foods for healthy individuals to prevent bone and vascular disease, as well as for patients on oral anticoagulant treatment to offer them protection against coumarin-induced side effects and to reduce diet-induced fluctuations in their INR values.

Topics: Animals; Blood Coagulation; Calcium-Binding Proteins; Drug Therapy, Combination; Extracellular Matrix Proteins; Humans; Matrix Gla Protein; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Animals; Anticoagulants; Calcinosis; Chronic Disease; Humans; Renal Dialysis; Renal Insufficiency; Vascular Diseases; Vitamin K; Vitamin K Deficiency; Warfarin

Vitamin K's effects extend beyond blood clotting to include a role in bone metabolism and potential protection against osteoporosis. Vitamin K is required for the gamma-carboxylation of osteocalcin. Likewise, this gamma-carboxylation also occurs in the liver for several coagulation proteins. This mechanism is interrupted by coumarin-based anticoagulants in both the liver and bone.. A thorough review of the literature on vitamin K, osteocalcin and their role in bone metabolism and osteoporosis, as well as the potential bone effects of anticoagulant therapy was conducted.. Epidemiological studies and clinical trials consistently indicate that vitamin K has a positive effect on bone mineral density and decreases fracture risk. Typical dietary intakes of vitamin K are below the levels associated with better BMD and reduced fracture risk; thus issues of increasing dietary intakes, supplementation, and/or fortification arise. To effectively address these issues, large-scale, intervention trials of vitamin K are needed. The effects of coumarin-based anticoagulants on bone health are more ambiguous, with retrospective studies suggesting that long-term therapy adversely affects vertebral BMD and fracture risk. Anticoagulants that do not affect vitamin K metabolism are now available and make clinical trials feasible to answer the question of whether coumarins adversely affect bone. The research suggests that at a minimum, clinicians should carefully assess anticoagulated patients for osteoporosis risk, monitor BMD, and refer them to dietitians for dietary and supplement advice on bone health. Further research is needed to make more efficacious decisions about vitamin K intake, anticoagulant therapy, and bone health.

Topics: Anticoagulants; Bone and Bones; Bone Density; Coumarins; Humans; Nutritional Requirements; Osteocalcin; Osteoporosis; Risk Factors; Time Factors; Vitamin K; Vitamin K Deficiency

Undercarboxylated osteocalcin (ucOC) is a sensitive marker of vitamin K (VK) status. Serum ucOC concentration in perimenopausal women is significantly higher than that in premenopausal women. In addition, serum ucOC concentration is closely associated with not only FSH concentration but also estradiol concentration. Serum ucOC concentration rapidly increases in women after bilateral oophorectomy. The effect of hormone therapy (HT) on alternate days on ucOC concentration is weaker than the effect of HT daily and ucOC concentration after 12 months of HT daily may be decreased due to the conversion of ucOC to carboxylated OC by the effect of VK through increased TG induced by oral conjugated equine estrogen (CEE) . Additionally, the effect of HT with transdermal estradiol on ucOC concentration in women is weaker than the effect of HT with oral CEE.

Topics: Biomarkers; Estradiol; Estrogen Replacement Therapy; Female; Femoral Neck Fractures; Follicle Stimulating Hormone; Humans; Menopause; Osteocalcin; Osteoporosis, Postmenopausal; Ovariectomy; Risk; Triglycerides; Vitamin K; Vitamin K Deficiency

Vitamin K (VK) is well known for its role in the synthesis of a number of blood coagulation factors. VK is also an important factor for bone metabolism via gamma-carboxylation of VK-dependent proteins such as osteocalcin, matrix Gla protein, and protein S. Recently, it is rare that severe VK deficiency is observed. However, low dietary VK intake or low VK status has been shown to be associated with low bone mineral density and increased hip fracture risk. These studies suggest that there is potential VK insufficiency in bone, even in sufficient VK status for blood coagulation. In the present review, the studies concerning relationship between serum VK concentration and bone health, including pharmacokinetics of VK analogues (such as phylloquinone and menaquinone) and factors which affect on blood circulation of VK, are reviewed.

Topics: Adult; Aged; Biomarkers; Bone and Bones; Bone Density; Calcium-Binding Proteins; Extracellular Matrix Proteins; Female; Hip Fractures; Humans; Male; Matrix Gla Protein; Middle Aged; Nutrition Assessment; Osteocalcin; Osteoporosis; Risk; Vitamin K; Vitamin K Deficiency

Biliary atresia (BA) is a rare disease, characterized by progressive and obliterative cholangiopathy, and is one of the major causes of secondary vitamin K deficiency in infancy. We describe 15 infants (10 female, 5 male) with BA, presenting with intracranial hemorrhage (ICH), including 10 subdural hemorrhages, 4 subarachnoid hemorrhages, 2 intraventricular hemorrhages, and 1 intraparenchymal hemorrhage. The age at onset of ICH ranged from 26 to 79 (mean 54.2) days. Eight patients underwent successful surgical evacuation of ICH, following administration of vitamin K. All 15 patients underwent Kasai portoenterostomy for BA 8-30 days after onset. During a mean follow-up period of 86.8 (range 2-352) months, 4 patients died of liver failure despite lack of neurological sequelae. Two patients underwent living-related donor and 1 patient living-unrelated donor liver transplantation. Only 2 patients suffered neurological signs and symptoms, including mental retardation and epilepsy, whereas 3 were noted to have temporary hemiparesis which recovered completely during the follow-up period. The possibility of BA should be considered in the treatment of ICH due to vitamin K deficiency, since it is reported to be one of the major causes of secondary vitamin K deficiency. Urgent surgical intervention for ICH can be performed successfully following sufficient administration of vitamin K or fresh frozen human plasma. Moreover, early performance of Kasai portoenterostomy is possible even for patients who have undergone craniotomy.

Topics: Biliary Atresia; Epilepsy; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Intellectual Disability; Intracranial Hemorrhages; Liver Failure; Liver Transplantation; Male; Paresis; Vitamin K; Vitamin K Deficiency; Vitamins

Calcium intake was reported to be associated with peak bone mass. Vitamin D insufficiency, which is less severe than deficiency, is prevalent in the elderly and known to cause osteoporosis. Protein malnutrition increases the fracture risk due to decreased bone mineral density and muscle weakness. Other nutrients have also been reported to be associated with osteoporosis. Thus nutritional aspect of osteoporosis should be interpreted from the broader perspectives. Since nutritional status greatly varies from one nation to another, we must add our original evidence in Japan to the report from WHO.

Topics: Calcium; Calcium, Dietary; Dietary Proteins; Humans; Japan; Nutritional Physiological Phenomena; Nutritional Status; Osteoporosis; Protein Deficiency; Vitamin D; Vitamin D Deficiency; Vitamin K; Vitamin K Deficiency; World Health Organization

This paper reviews the interventions to stabilize calcium balance and bone metabolism and prevent bone loss in astronauts during space flight. Weightlessness during space flight results in calcium, vitamin D, and vitamin K deficiency, increases urinary calcium excretion, decreases intestinal calcium absorption, and increases serum calcium level, with decreased levels of serum parathyroid hormone and calcitriol. Bone resorption is increased, whereas bone formation is decreased. The loss of bone mineral density (BMD) in the spine, femoral neck and trochanter, and pelvis is 1.0-1.6% per month. High calcium intake and vitamin D supplementation during space flight does not affect bone metabolism, but prevents an elevation of serum calcium level through increased calcitriol level, while vitamin K counteracts the reduction in bone formation. However, there are no data to show the efficacy of pharmaceutical agents for prevention of development of osteoporosis in astronauts during flight, although the preventative effect of bisphosphonates, testosterone, and vitamin K2 on cancellous bone loss in the tibia or BMD loss in the hindlimb was reported in tail-suspended mature rats. It still remains uncertain whether these agents can prevent cortical bone loss caused by weightlessness in tail-suspended rats. Therefore, in addition to calcium, vitamin D, and vitamin K supplementation, agents that have both potent anti-resorptive and anabolic effects on cancellous and cortical bone may be needed to stabilize calcium balance and bone metabolism and prevent bone loss in astronauts during space flight.

Topics: Aerospace Medicine; Animals; Astronauts; Biomarkers; Bone and Bones; Bone Density; Bone Resorption; Calcium; Calcium, Dietary; Dietary Supplements; Diphosphonates; Energy Intake; Humans; Osteoporosis; Rats; Sodium Chloride, Dietary; Space Flight; Testosterone; Vitamin D; Vitamin D Deficiency; Vitamin K; Vitamin K 2; Vitamin K Deficiency; Weightlessness; Weightlessness Countermeasures; Weightlessness Simulation

There has been relatively little research emphasis on the effect of vitamin K on bone health during childhood. Recent interesting data from an observational study of healthy young girls (aged 3-16 years) in the United States suggests that better vitamin K status is associated with lower levels of markers of bone resorption and bone formation, suggesting a lower rate of bone turnover. However, in that study, vitamin K status was not consistently associated with bone mineral content or gain in bone mineral content over 4 years. There is a need for randomized phylloquinone supplementation trials to better understand the role of vitamin K on bone acquisition in growing children.

Topics: Adult; Bone and Bones; Bone Density; Bone Development; Child; Female; Humans; Male; Nutritional Status; Vitamin K; Vitamin K Deficiency; Vitamins

Topics: Cystic Fibrosis; Humans; Vitamin K; Vitamin K Deficiency

Vitamin K is well known for its role in the synthesis of a number of blood coagulation factors. During recent years vitamin K-dependent proteins were discovered to be of vital importance for bone and vascular health. Recommendations for dietary vitamin K intake have been made on the basis of the hepatic requirements for the synthesis of blood coagulation factors. Accumulating evidence suggests that the requirements for other functions than blood coagulation may be higher. This paper is the result of a closed workshop (Paris, November 2002) in which a number of European vitamin K experts reviewed the available data and formulated their standpoint with respect to recommended dietary vitamin K intake and the use of vitamin K-containing supplements.

Topics: Antifibrinolytic Agents; Arteriosclerosis; Bone and Bones; Calcinosis; Dietary Supplements; Fractures, Bone; Humans; Nutritional Requirements; Osteocalcin; Osteoporosis; Safety; Vitamin K; Vitamin K Deficiency

To assess growing evidence that vitamin K (phylloquinone) plays an important role in bone health and, subsequently, in prevention of osteoporotic fractures.. We searched MEDLINE from January 1972 to December 2002 using the key words vitamin K and bone health. We reviewed 30 articles that seemed relevant or had a human focus. All evidence can be categorized as level II.. Evidence suggests that dietary phylloquinone intake of <100 microg daily might not be optimal for bone health. Low intake of vitamin K could contribute to osteoporosis and subsequent fracture due to the undercarboxylation of osteocalcin.. Family physicians need to be aware of the importance of encouraging adequate vitamin K intake, particularly among institutionalized elderly people, to prevent increased bone resorption. Further study is needed to determine the exact role of vitamin K in bone metabolism, and methods of assessing vitamin K requirements need to be standardized.

Topics: Aged; Bone Resorption; Clinical Trials as Topic; Epidemiologic Studies; Family Practice; Female; Fractures, Bone; Humans; Male; Nutrition Policy; Osteocalcin; Osteoporosis; Vitamin K; Vitamin K Deficiency

Several acquired bleeding disorders in the developing world have impacts on health, including late vitamin K deficiency bleeding (VKDB) in infants, dengue haemorrhagic fever (DHF), and malaria. This paper describes their clinical manifestations, mechanisms involved, and treatment.

Topics: Antimalarials; Blood Coagulation Disorders; Developing Countries; Hemorrhage; Humans; Infant; Infant, Newborn; Malaria, Falciparum; Risk Factors; Severe Dengue; Vitamin K; Vitamin K Deficiency

Topics: Aging; Anti-Bacterial Agents; Biomarkers; Chromatography, High Pressure Liquid; Electrochemistry; Humans; Kidney Diseases; Neoplasms; Protein Precursors; Prothrombin; Reference Values; Risk Factors; Specimen Handling; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

Osteoporosis is a serious public health concern. Skeletal fragility, leading to spine and hip fractures, is a major source of morbidity and mortality. Adequate calcium intake from childhood to the end of life is critical for the formation and retention of a healthy skeleton. It is important to prevent bone loss from occurring, to identify potential risk factors, and to correct them. Many genetic and lifestyle factors influence the risk for osteoporosis. Among these, diet is believed to be one of the most important, especially the roles of calcium and vitamin D. Deficiency in other dietary factors--eg, protein, vitamin K, vitamin A, phytoestrogens, and other nutrients--might also contribute to the risk for osteoporosis. In this article, the roles of diet and nutritional supplementation in preventing and treating osteoporosis are reviewed.

Topics: Adolescent; Adult; Aged; Bone and Bones; Calcium, Dietary; Child; Child, Preschool; Diet; Dietary Supplements; Estrogens, Non-Steroidal; Female; Fractures, Bone; Humans; Infant; Infant, Newborn; Isoflavones; Life Style; Male; Middle Aged; Nutritional Requirements; Nutritional Status; Osteoporosis; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Quality of Life; Risk Factors; United States; Vitamin A; Vitamin A Deficiency; Vitamin D; Vitamin D Deficiency; Vitamin K; Vitamin K Deficiency

Vitamin K-deficiency bleeding (VKDB) is rare, unpredictable, and life-threatening. Warning signs such as minimal bleeds, evidence of cholestasis, and failure to thrive often are present but overlooked. Therefore VK prophylaxis is necessary, at least for breastfed infants. Most effective is the intramuscular application, which unfortunately has real disadvantages (trauma, poor acceptance by parents) and potential risks due to very high VK levels, since VK affects not only coagulation but all processes associated with carboxylation. Three oral doses of VK protect many babies (2-mg doses giving better protection than 1 mg) but the prevention of VKDB is not assured even with the mixed-micelle preparation. Use of small VK doses either daily or weekly seems to give effective prophylaxis without the adverse effects of intramuscular VK application. The risks of VKDB are minimized if prophylaxis recommendations are followed and if warning signs are recognized and promptly acted upon. The next goal is the search for methods of identifying early the few infants destined to bleed so that targeted prophylaxis can replace the current "prophylaxis for all."

Topics: Child; Hemorrhage; Humans; Infant, Newborn; Practice Guidelines as Topic; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Calcification, Physiologic; Dietary Supplements; Humans; Nutritional Requirements; Nutritional Status; Osteocalcin; Risk Factors; Vitamin K; Vitamin K Deficiency

Vitamin K-dependent factors are lower in neonates than in adults, and these anomalies are more prevalent in preterm neonates and in breast-fed infants. Vitamin K deficiency can account for vitamin K deficiency bleeding (VKDB) which occurs in 3 forms--early, classic and late. Vitamin K should be administered to all neonates at birth or immediately afterwards. However, the protocols for administration (route of administration, dosage, number of doses) remain a subject of discussion. Oral administration of a single dose of vitamin K protects against classical and early VKDB, but is less effective than intramuscular (IM) prophylaxis for the prevention of late VKDB. Although an increased risk of solid tumour, associated vitamin K administration, can be definitively excluded, a low potential risk of lymphoblastic leukaemia in childhood can not be ruled out. For formula-fed neonates without risk of haemorrhage, a 2 mg oral dose of vitamin K at birth, followed by a second 2 mg oral dose between day 2 and 7, is probably sufficient to prevent VKDB. For infants who are exclusively or nearly exclusively breast-fed, weekly oral administration of 2mg (or 25 microg/day) vitamin K after the initial 2 oral doses is justified at completion of breast-feeding. For neonates at high risk of haemorrhage (premature, neonatal disease, birth asphyxia, difficult delivery, any illness which will delay feeding, known hepatic disease, maternal drugs inhibiting vitamin K activity), the first dose must be administered by the IM or slow intravenous route. Doses should be repeated, particularly in premature infants, by a route of administration decided for each dose according to the clinical state of the infant. For infants of mothers treated with drugs inhibiting vitamin K activity, antenatal maternal prophylaxis (10 to 20 mg/day orally for 15 to 30 days before delivery) prevents early VKDB. After neonatal prophylaxis, as for infants at high risk of haemorrhage, doses need to be repeated at a rate and route of administration decided for each dose, according to the clotting factor profile specific for each infant.

Topics: Anticonvulsants; Female; Hemorrhage; Humans; Infant, Newborn; Neoplasms; Pregnancy; Prenatal Care; Risk Factors; Vitamin K; Vitamin K Deficiency

Anaphylactoid reactions in patients receiving intravenously administered vitamin K have been reported in the literature. To summarize the known data on anaphylactoid reactions from administration of vitamin K, we reviewed all published and unpublished reports of this adverse reaction. Published reports were obtained through medline (1966--1999) and EMBASE (1971--1999) searches of the English language literature and review of references from identified case reports. Unpublished reports were obtained using the Spontaneous Reporting System Adverse Reaction database of the United States Food and Drug Administration (FDA) between August 1968 and September 1997. All adverse drug reactions to vitamin K were categorized by route of drug administration, dose and standard adverse reaction code. In the FDA reports, we defined anaphylactoid reactions as any adverse drug reaction coded as either anaphylaxis, allergic reaction, apnea, dyspnea, death, heart arrest, hypotension, shock or vasodilatation. Additionally, all fatal and life-threatening FDA reported reactions were reviewed to determine if they could represent an anaphylactoid reaction missed by the above definition. The literature review uncovered a total of 23 cases (3 fatal) of anaphylactoid reactions from intravenous vitamin K. The FDA database contained a total of 2236 adverse drug reactions reported in 1019 patients receiving vitamin K by all routes of administration. Of the 192 patients with reactions reported for intravenous vitamin K, 132 patients (69 %) had a reaction defined as anaphylactoid, with 24 fatalities (18 %) attributed to the vitamin K reaction. There were 21 patients with anaphylactoid reactions and 4 fatalities reported with doses of intravenous vitamin K of less than 5 mgs. For the 217 patients with reactions reported due to vitamin K via a non-intravenous route of administration, 38 patients had reactions meeting the definition of anaphylactoid (18 %), with 1 fatality (3 %) attributed to the drug. The absolute risk of an anaphylactoid reaction to intravenous vitamin K cannot be determined by this study, but the relatively small number of documented cases despite widespread use of this drug suggest that the reaction is rare. Anaphylactic reactions and case fatality reports were found even when intravenous vitamin K was given at low doses by slow dilute infusion. The pathogenesis of this reaction is unknown and may be multifactorial with etiologies including vasodilation induced by the so

Topics: Adverse Drug Reaction Reporting Systems; Anaphylaxis; Animals; Anticoagulants; Drug Administration Routes; Drug Hypersensitivity; Drug Interactions; Hemorrhage; Humans; United States; United States Food and Drug Administration; Vasodilation; Vitamin K; Vitamin K Deficiency

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Humans; Liver Diseases; Liver Transplantation; Vitamin K; Vitamin K Deficiency

Topics: Anticonvulsants; Humans; Infant, Newborn; Prognosis; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Vitamin K deficiency can cause bleeding in an infant in the first weeks of life. This is known as Hemorrhagic Disease of the Newborn (HDN). HDN is divided into three categories: early, classic and late HDN. Early HDN occurs within 24 hours post partum and falls outside the scope of this review. Classic HDN occurs on days one to seven; common bleeding sites are gastrointestinal, cutaneous, nasal and from a circumcision. Late HDN occurs from week 2-12; the most common bleeding sites are intracranial, cutaneous, and gastrointestinal. Vitamin K is commonly given prophylactically after birth for the prevention of HDN, but the preferred route is uncertain.. To review the evidence from randomized trials in order to determine the effectiveness of vitamin K prophylaxis in the prevention of classic and late HDN. Main questions are: Is one dose of vitamin K, given after birth, able to significantly reduce the incidence of classic and late HDN? Is there a significant difference between the oral route and the intramuscular route in preventing classic and late HDN? Are multiple oral doses of vitamin K, given after birth, able to significantly reduce the incidence of classic and late HDN?. The standard search strategy of the Cochrane Neonatal Review Group was used.. All trials using random or quasi-random patient allocation, in which methods of vitamin K prophylaxis in infants were compared to each other, placebo or no treatment, were included.. Data were extracted independently by each author and were analysed with the standard methods of the Cochrane Collaboration and its Neonatal Review Group, using relative risk, risk difference and weighted mean difference.. Two eligible randomized trials, each comparing a single dose of intramuscular vitamin K with placebo or nothing, assessed effect on clinical bleeding. One dose of vitamin K reduced clinical bleeding at 1-7 days, including bleeding after circumcision, and improved biochemical indices of coagulation status. Eleven additional eligible randomized trials compared either a single oral dose of vitamin K with placebo or nothing, a single oral with a single intramuscular dose of vitamin K, or three oral doses with a single intramuscular dose. None of these trials assessed clinical bleeding. Oral vitamin K improved biochemical indices of coagulation status at 1-7 days. There was no evidence of a difference between the oral and intramuscular route in effects on biochemical indices of coagulation status. A single oral compared with a single intramuscular dose resulted in lower plasma vitamin K levels at two weeks and one month, whereas a 3-dose oral schedule resulted in higher plasma vitamin K levels at two weeks and at two months than did a single intramuscular dose.. A single dose (1.0 mg) of intramuscular vitamin K after birth is effective in the prevention of classic HDN. Either intramuscular or oral (1.0 mg) vitamin K prophylaxis improves biochemical indices of coagulation status at 1-7 days. Neither intramuscular nor oral vitamin K has been tested in randomized trials with respect to effect on late HDN. Oral vitamin K, either single or multiple dose, has not been tested in randomized trials for its effect on either classic or late HDN.

Topics: Humans; Infant, Newborn; Infant, Premature; Randomized Controlled Trials as Topic; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Administration, Oral; Female; Humans; Infant, Newborn; Injections, Intramuscular; Male; Neoplasms; Risk Factors; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Newborn babies are born vitamin K deficient; however, the deficiency is not sufficiently severe to cause a vitamin K deficiency coagulopathy and haemorrhagic disease of the newborn (HDN). Severe vitamin K deficiency can develop quickly in breast-fed newborns and can result in the appearance of classic HDN during the first week of life or late HDN during the first 2 months of life. Both forms of the disease can be severe, causing brain damage and death. Classic and late HDN are prevented by the intramuscular administration of vitamin K at birth. Oral prophylaxis prevents classic HDN but is ineffective in preventing late HDN. Despite proven effectiveness of intramuscular vitamin K prophylaxis there have been concerns about the need for, and safety of, this therapy. This review provides evidence that there is need for intramuscular vitamin K prophylaxis for all babies in order to eradicate haemorrhagic disease of the newborn and concludes that there is no evidence that this therapy is harmful.

Topics: Administration, Oral; Blood Coagulation; Humans; Infant, Newborn; Injections, Intramuscular; Neoplasms; Risk Factors; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Vitamin K deficiency remains a world-wide problem in the newborn. Vitamin K traverses the placenta from mother to infant very poorly and is present only in very low concentrations in human milk. Thus, it is not surprising that the newborn infant has undetectable vitamin K serum levels with abnormal amounts of the coagulation proteins and undercarboxylated prothrombin. Hemorrhagic disease of the newborn, secondary to vitamin K deficiency, remains largely a disease of breastfed infants. Lactating mothers easily achieve the recommended dietary allowance for vitamin K (1 microg kg(-1) d(-1)) and the breast milk concentration is readily increased by increasing maternal vitamin K intake. Breastfed infants do not receive the recommended vitamin K intake via human milk. To prevent vitamin K deficiency in the newborn, intramuscular or oral vitamin K prophylaxis is necessary.

Topics: Adult; Breast Feeding; Comorbidity; Female; Humans; Incidence; Infant, Newborn; Male; Milk, Human; Neoplasms; Randomized Controlled Trials as Topic; Risk Assessment; Socioeconomic Factors; United States; Vitamin K; Vitamin K Deficiency; World Health Organization

The current daily recommended dietary allowance for vitamin K is 1 microg/kg. Reliable measurements of vitamin K content in foods are now available, and data from 11 studies of vitamin K intake indicate that the mean intake of young adults is approximately 80 microg phylloquinone/d and that older adults consume approximately 150 microg/d. The vitamin K concentration in most foods is very low (<10 microg/100 g), and the majority of the vitamin is obtained from a few leafy green vegetables and four vegetable oils (soybean, cottonseed, canola and olive) that contain high amounts. Limited data indicate that absorption of phylloquinone from a food matrix is poor. Hydrogenated oils also contain appreciable amounts of 2', 3'-dihydrophylloquinone of unknown physiological importance. Menaquinones absorbed from the diet or the gut appear to provide only a minor portion of the human daily requirement. Measures of the extent to which plasma prothrombin or serum osteocalcin lack essential gamma-carboxyglutamic acid residues formed by vitamin K action, or the urinary excretion of this amino acid, provide more sensitive measures of vitamin K status than measures of plasma phylloquinone or insensitive clotting assays.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Diet; Female; Humans; Male; Middle Aged; Nutrition Policy; Vitamin K; Vitamin K Deficiency

Vitamin K deficiency leads to a deficit in vitamin K-dependent factors, resulting in either hypocoagulability and a decrease in the Quick one-stage prothrombin time expressed as the prothrombin time (PT), or in an increase in INR in patients receiving oral anticoagulation. The anesthesiologist's objective is to bring these values back into the safety range before surgery, i.e., above 50% for PT and below 1.5 for INR. The method to be used will be chosen according to the urgency of the correction. Safety ranges may be reached in 6-12 h following oral or parenteral administration of vitamin K. A 5-mg dose is usually sufficient. If the deficit in vitamin K-dependent factors requires immediate correction, intravenous administration of PPSB should be done. The minimum time during which antivitamin K treatment may be disrupted after surgery depends on both the possibility of restarting oral treatment and the risk of postoperative haemorrhage. During this period, the need for an anticoagulation treatment using heparin should be discussed according to the risk of thrombosis.

Topics: Blood Loss, Surgical; Coagulants; Humans; Risk Factors; Vitamin K; Vitamin K Deficiency

Vitamin K is a cofactor for the synthesis of blood coagulation Factors II, VII, IX and X, and inhibitors such as Protein C and S and bone matrix protein. Its active form is a coenzyme in the glutamic acid carboxylation. Vitamin K-dependent factors form enzymatic complexes with calcium and membrane phospholipids. The insufficiency of gamma glutamic carboxylation impairs the hemostatic function. Hereditary deficiencies, antibiotics and oral anticoagulants, decrease the capacity of complex formation giving way to hemorrhage or thrombosis, or bone mass disturbances which are easily treated with administration of Vitamin K. The main causes of Vitamin K deficiency are lack of hepatic storage in newborns, liver insufficiency, malabsorption, dietetic deficiency, therapy with the antibiotics and coumarin administration. For the study of Vitamin K there are methods to measure the Vit K dependent proteins and as well methods to measure specifically the quinonas.

Topics: Adult; Anticoagulants; Blood Coagulation; Blood Coagulation Factors; Coumarins; Enzymes; Humans; Infant, Newborn; Intestinal Absorption; Liver Diseases; Models, Biological; Osteocalcin; Vitamin K; Vitamin K Deficiency

Topics: Breast Feeding; Hemostatics; Humans; Infant, Newborn; Nurse Midwives; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Although the abundance of vitamin K-dependent proteins in bone suggests an important function, the precise role of vitamin K in skeletal health remains to be determined. Serum concentrations of vitamin K are reportedly reduced in older individuals and persons with osteoporotic fracture. Whether this is causally related to vitamin K insufficiency or simply reflects inadequate nutritional status is unclear. Circulating levels of undercarboxylated osteocalcin may be a sensitive marker of vitamin K inadequacy and have been reported to be increased in both postmenopausal women and individuals who sustained hip fracture. It is also possible that vitamin K indirectly affects the skeleton via control of renal calcium excretion. The effect of vitamin K antagonists (oral anticoagulants) on both renal calcium excretion and bone density is controversial. Thus, many of the reports implicating a role for vitamin K insufficiency in the development of osteoporosis are conflicting. This review summarizes current knowledge regarding a possible role of vitamin K insufficiency in the pathogenesis of osteoporosis.

Topics: Aged; Amino Acid Sequence; Calcium-Binding Proteins; Extracellular Matrix Proteins; Female; Humans; Matrix Gla Protein; Middle Aged; Molecular Sequence Data; Nutritional Physiological Phenomena; Osteocalcin; Osteoporosis; Vitamin K; Vitamin K Deficiency

Vitamin K is a fat-soluble vitamin crucial to the production of many proteins involved with the coagulation process. It is integral in the synthesis of coagulants (factors II, VII, IX and X) and anticoagulants (proteins C and S). It is generally recognised that routine administration of vitamin K (phytomenadione) shortly after birth will prevent major neonatal morbidity and mortality related to haemorrhage. Vitamin K supplementation during pregnancy is also recommended if mothers are on anticonvulsant therapy or prolonged treatment with certain antibiotics. These medications, if ingested by pregnant women, predispose the neonate to a bleeding tendency caused by vitamin K deficiency. Vitamin K treatment of pregnant mothers before premature delivery has also been suggested to reduce the incidence of severe intracranial haemorrhage (ICH) in premature neonates. Although further studies are pending, the data to date do not support using antenatal vitamin K for preventing ICH.

Topics: Anticonvulsants; Cerebral Hemorrhage; Epilepsy; Female; Hemorrhage; Humans; Infant, Newborn; Infant, Premature, Diseases; Leukemia; Placenta; Pregnancy; Pregnancy Complications; Vitamin K; Vitamin K Deficiency

Topics: Biological Transport; Blood Coagulation; Bone and Bones; Bone Development; Calcium; Food Analysis; Humans; Infant, Newborn; Nutritional Requirements; Osteocalcin; Risk Factors; Tissue Distribution; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Hemorrhage in the infant from vitamin K deficiency is still a concern in pediatrics. Vitamin K given intramuscularly will largely prevent hemorrhagic disease in the newborn, even in infants who are exclusively breast-fed and are thus at the greatest risk for bleeding. The vitamin K content of human milk is very low compared with standard infant formulas. Results with oral vitamin K prophylaxis, currently used in some countries following the association found in a single report between childhood cancer and intramuscular vitamin K, are far more controversial. Any role of vitamin K in the prevention of IVH in premature infants has not been sufficiently demonstrated. Ongoing developments in this field will lead to improved methods of detecting early vitamin K deficiency and perhaps suitable alternatives to intramuscular vitamin K prophylaxis in the newborn.

Topics: Cerebral Hemorrhage; Humans; Infant, Newborn; Infant, Premature, Diseases; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Vitamin K is a cofactor required for the formation of gamma-carboxyglutamate (Gla) residues in proteins. Osteoblasts produce at least three different Gla-containing proteins: osteocalcin, matrix Gla-protein, and protein S. After cellular secretion of these proteins, the main part of each remains bound to the hydroxyapatite matrix in bone, but their function remains unclear. Part of the newly synthesized osteocalcin is also set free into the bloodstream, where it may be used as a diagnostic marker for bone formation. Several studies have demonstrated that a poor vitamin K status is associated with an increased risk of osteoporotic bone fractures. Whether vitamin K supplementation will reduce the rate of bone loss in postmenopausal women remains a matter of debate.

Topics: Animals; Bone and Bones; Humans; Osteocalcin; Rats; Vitamin K; Vitamin K Deficiency

Ten patients with maxillonasal hypoplasia (Binder "syndrome"), who were prenatally exposed to phenytoin (usually in combination with other anticonvulsants), were identified retrospectively. In addition to their facial anomalies, 6 of the patients were radiographed neonatally and showed punctate calcification, characteristic of chondrodysplasia punctata. Evidence is presented that the facial abnormalities seen in these children are due to anticonvulsant-induced vitamin K deficiency, causing abnormal development of the cartilaginous nasal septum. We propose that early vitamin K supplementation of at-risk pregnancies may prevent the development of maxillonasal hypoplasia, which in some patients is severely disfiguring and causes great emotional distress. Correction of this facial defect requires surgical and dental treatment over a long period of time.

Topics: Abnormalities, Drug-Induced; Adult; Anticonvulsants; Child; Chondrodysplasia Punctata; Face; Female; Humans; Infant; Infant, Newborn; Male; Phenytoin; Pregnancy; Prenatal Exposure Delayed Effects; Vitamin K; Vitamin K Deficiency

Dicoumarol was found to be the causative agent of a haemorrhagic disease in cattle following the ingestion of spoiled sweet clover. Vitamin K deficiency in chickens caused bleeding. Dicoumarol was later determined to be a vitamin K antagonist. A more potent form of the drug was produced synthetically and, following its initial use as rat poison, was recognized as a potential anti-thrombotic treatment in humans. The mode of action of a coumarin derivative (i.e. warfarin) is described. The overall effect of high-dose and low-dose warfarin and the possibility of a transient state of hypercoagulability on the introduction and withdrawal of treatment is considered.

Topics: Animals; Anticoagulants; Blood Coagulation Factors; Coumarins; Hemostasis; Humans; Protein C; Protein S; Vitamin K; Vitamin K Deficiency; Warfarin

The microsomal mixed function oxidase system metabolizes xenobiotics (Phase I) to products that, if not activated and conjugated for excretion (Phase II), are capable of forming conjugates with cellular macromolecules, including DNA, resulting in toxic, mutagenic, or carcinogenic events. Benzo(a)pyrene (BP), a polycyclic aromatic hydrocarbon, is a model carcinogen for this system. Vitamin K1 (phylloquinone) is a regulator of BP metabolism. These studies demonstrate that K1 is capable of increasing Phase I metabolism and decreasing glutathione transferase activity (Phase II) in chick embryo liver; that deprivation of K1 reduces BP/DNA adducts in mouse liver and reduces tumor formation in mice given intraperitoneal BP; and that K1 supplementation increases BP induced tumor formation in mice. However, epidemiologic studies indicate that children of mothers who smoke during pregnancy may not be at increased risk of cancer. It is known that the placentas from these pregnancies exhibit markedly increased levels of arylhydrocarbon hydroxylase induced by the polycyclic aromatic hydrocarbons in tobacco smoke, but there is no corresponding increase in this enzyme activity in the fetus in such pregnancies. We suggest that the low vitamin K level is a secondary protective mechanism for xenobiotics, such as BP, that may escape the primary placental screen. The recently described role of vitamin K-dependent Gla protein as ligands for receptor tyrosine kinases, also establishes K as a link in cell growth and transformation. It is proposed that the small total body pool of K1 in the adult, which is sufficient only to meet continuing needs, and the even smaller pool in the fetus are protective. This protective effect of low K1 levels is particularly important in the presence of the high mitotic rates and rapid cell turnover in the avian embryo and mammalian fetus.

Topics: 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; Adult; Animals; Biotransformation; Carcinogens; Chick Embryo; Cocarcinogenesis; DNA Adducts; Female; Fetal Diseases; Fetus; Humans; Infant, Newborn; Liver; Maternal Exposure; Maternal-Fetal Exchange; Mice; Mice, Inbred ICR; Microsomes, Liver; Mixed Function Oxygenases; Neoplasms; Neoplasms, Experimental; Placenta; Pregnancy; Prenatal Exposure Delayed Effects; Smoking; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Warfarin; Xenobiotics

Coumarin derivatives and anticonvulsants administered during pregnancy enter the fetal circulation, interfering with the action of vitamin K. Vitamin K plays a crucial part in the gamma-carboxylation of glutamic acid residues of the vitamin K-dependent coagulation factors prothrombin, FVII, FIX, and FX. Other vitamin K-dependent proteins in the coagulation cascade are protein C and protein S. Vitamin K-dependent bone proteins are osteocalcin and gamma-carboxyglutamate matrix protein. Administration of coumarol derivatives results in under carboxylation of the vitamin K-dependent proteins. Anticoagulation therapy with warfarin is followed by an increased risk of embryopathy, which has been shown to be greatest between gestational weeks 6 and 12. Administration of warfarin is also followed by an increased risk both of fetal intraventricular hemorrhage, and of cerebral microbleedings, which may result in microencephaly and mental retardation. Treatment with coumarol derivatives should therefore be avoided during pregnancy, even in pregnant women with artificial heart valves, and replaced by heparin. Hemorrhage in the newborn related to the use of anticonvulsant drugs during pregnancy occurs very early within the first 24 hours, probably due to increased degradation of vitamin K. Transplacental administration of vitamin K has been shown to prevent neonatal hemorrhage induced by maternal anticonvulsant therapy. Prophylactic administration of vitamin K, especially by intramuscular injection, has been reported to be associated with an increased risk of childhood cancer. However, subsequent extensive studies have yielded no evidence of any relationship between prophylactic vitamin K administration and the occurrence of childhood cancer.

Topics: Abnormalities, Drug-Induced; Anticoagulants; Anticonvulsants; Blood Coagulation Factors; Child; Cohort Studies; Coumarins; Epilepsy; Female; Fetal Diseases; Hemorrhage; Humans; Infant, Newborn; Maternal-Fetal Exchange; Neoplasms; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Protein Processing, Post-Translational; Sweden; Thrombosis; United Kingdom; Vitamin K; Vitamin K Deficiency

A substantial effort has been made over the past decade to characterize the metabolism of the fat-soluble vitamins in chronic cholestasis to both improve the clinical care of affected patients and to understand the pathophysiology of the vitamin deficiency states. Cholestatic liver disease is a unique cause of fat malabsorption in which standard indices to evaluate vitamin status may be inaccurate. Thus, specific approaches to define vitamin status are being developed. Using the treatment modalities outlined in this review, fat-soluble vitamin deficiency should be a manageable problem and not lead to significant morbidity in patients with chronic cholestasis. The most subtle consequences of deficiency of each vitamin remains to be discovered.

Topics: Child; Cholestasis, Intrahepatic; Humans; Intestinal Absorption; Vitamin A; Vitamin A Deficiency; Vitamin D; Vitamin D Deficiency; Vitamin E; Vitamin E Deficiency; Vitamin K; Vitamin K Deficiency; Vitamins

To assess the advisability of routine vitamin K supplementation in patients with cystic fibrosis (CF).. Studies identified through a MEDLINE search with the use of MeSH terms vitamin K, cystic fibrosis, PIVKA-II (protein induced by vitamin K absence-II), coagulation abnormality and cystic fibrosis, and hepatic disorder and cystic fibrosis.. Six articles published between January 1981 and December 1992 were selected: one general review of vitamin K in infancy and five studies involving clinical trials of vitamin K supplementation or screening for fat-soluble vitamins, vitamin K or PIVKA-II in patients with CF. Review articles on nutrition in patients with CF, technical reports, letters, comments and case studies not bearing directly on these issues were excluded.. Findings in these articles were analysed and compared to determine whether routine supplementation in all patients with CF is indicated, whether specific subgroups of these patients are susceptible to vitamin K deficiency and areas in which future research is needed.. There is no consensus on routine vitamin K supplementation in patients with CF. Studies have found a few cases of vitamin K deficiency among the population of people with CF. In addition, various factors--including pancreatic failure, liver disease, bowel resection and long-term use of antibiotics--can put some of these patients at risk of vitamin K deficiency.. Specific indications for routine vitamin K supplementation in all patients with CF have not yet been identified. Pending further studies, it would be prudent to consider routine supplementation in patients with CF and severe noncholestatic and cholestatic liver disease, major small-bowel resection, pancreatic insufficiency or lung disease necessitating frequent use of antibiotics. A stronger body of evidence is needed as a basis for clinical strategies.

Topics: Administration, Oral; Adolescent; Adult; Age Factors; Anti-Bacterial Agents; Biomarkers; Child; Child, Preschool; Clinical Trials as Topic; Cystic Fibrosis; Food, Fortified; Humans; Infant; Infant, Newborn; Protein Precursors; Prothrombin; Vitamin K; Vitamin K Deficiency

The normal vitamin K status of the human embryo appears to be close to deficiency. Maternal dietary deficiency or use of a number of therapeutic drugs during pregnancy, may result in frank vitamin K deficiency in the embryo. First trimester deficiency results in maxillonasal hypoplasia in the neonate with subsequent facial and orthodontic implications. A rat model of the vitamin K deficiency embryopathy shows that the facial dysmorphology is preceded by uncontrolled calcification in the normally uncalcified nasal septal cartilage, and decreased longitudinal growth of the cartilage, resulting in maxillonasal hypoplasia. The developing septal cartilage is normally rich in the vitamin K-dependent protein matrix gla protein (MGP). It is proposed that functional MGP is necessary to maintain growing cartilage in a non-calcified state. Developing teeth contain both MGP and a second vitamin K-dependent protein, bone gla protein (BGP). It has been postulated that these proteins have a functional role in tooth mineralization. As yet this function has not been established and abnormalities in tooth formation have not been observed under conditions where BGP and MGP should be formed in a non-functional form.

Topics: 1-Carboxyglutamic Acid; Animals; Calcium-Binding Proteins; Extracellular Matrix Proteins; Facial Bones; Female; Humans; Matrix Gla Protein; Osteocalcin; Pregnancy; Rats; Skull; Vitamin K; Vitamin K Deficiency

Discussion about the efficacy and safety of vitamin K prophylaxis has recently restarted. In this review, new developments in diagnosis of vitamin K deficiency (including vitamin K plasma levels and protein induced by vitamin K absence [PIVKA]-II detection) and therapy of early, classic, and late hemorrhagic disease of the newborn are highlighted. Special attention is brought to the efficacy of preventing early and late hemorrhagic disease. The recently described association between intramuscular vitamin K administration and cancer is debated. The very high plasma levels, the intramuscular injection itself, or the adjuvants in the solution might all be responsible. These factors are all absent in oral administration. Therefore, we recommend repeated oral administration for preventing classic and late hemorrhagic disease of the newborn. Additionally, we recommend maternal supplementation of vitamin K for preventing early hemorrhagic disease of the newborn, especially when the mother is using medications that interfere with vitamin K metabolism.

Topics: Administration, Oral; Clinical Protocols; Humans; Infant, Newborn; Injections, Intramuscular; Intestinal Absorption; Neoplasms; Primary Prevention; Risk Factors; Time Factors; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

To review the function of vitamin K in clotting and methods of its analysis, to present results of previous studies on the role of dietary vitamin K in humans and animals, and to reanalyze these data in light of current methods.. A review of assumptions stated in the literature is presented, including the incorrect theory that a diet-induced deficiency of vitamin K is nonexistent and the unsubstantiated hypothesis that antibiotics can cause vitamin K deficiency by destroying intestinal bacteria.. The insistent belief that intestinal bacteria are an important source of vitamin K has led to erroneous conclusions about the sources of vitamin K for human nutrition. In the future, the importance of various sources of vitamin K, their pathways of absorption, and their susceptibility to administration of antibiotics should be evaluated without recourse to current assumptions.

Topics: Animals; Bacteria; Disease Models, Animal; Humans; Intestines; Vitamin K; Vitamin K Deficiency

Vitamin K is given to many babies born in the United Kingdom, but we still do not know if it has substantial hazards. Because the population exposed to vitamin K is very large even quite small hazards would involve many adverse events. It is therefore important to be able to put reasonably close bounds on the potential damage that vitamin K prophylaxis could cause. Past research has not allowed us to do this but a large randomised controlled clinical trial of vitamin K against no vitamin K, enrolling only infants at low risk of haemorrhagic disease, would do so. There is no question that vitamin K is a useful treatment in babies at highest risk of haemorrhagic disease: the question is whether the trend towards use of vitamin K in lower risk babies should be encouraged.

Topics: Adolescent; Adult; Child; Child, Preschool; Clinical Trials as Topic; England; Humans; Incidence; Infant; Infant, Newborn; Neoplasms; Risk Factors; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding; Wales

Vitamin K (phylloquinone, K1; menaquinone, K2) functions as an essential cofactor for the synthesis of the coagulation protein factors II, VII, IX, X and protein C and S by promoting a unique post-translational modification of specific glutamic acid residues to gamma-carboxylglutamic acid, thus mediating calcium binding to phospholipid surfaces. Vitamin K deficiency results in a depletion of liver stores of phylloquinone, decreased plasma levels of vitamin K1, increased levels of K1 epoxide, appearance of noncarboxylated protein (PIVKA), decreased levels of functioning vitamin K-dependent clotting factors and prolongation of the APTT, PT and thrombotest. When the progression of deficiency leads to abnormal clotting tests a generalized bleeding tendency occurs. Noncarboxylated prothrombin (PIVKA-II) determinations are a sensitive indicator of vitamin K deficiency. Although Vitamin K deficiency can occur at any age (warfarin, fasting, antibiotic therapy, malabsorption syndromes) the major public health problem is related to prevention of early, classic and late hemorrhagic disease of the newborn (HDN). A single dose of oral or parenteral vitamin K prevents classic HDN but the most effective way to prevent early HDN is by giving large doses to the mother prior to delivery (2 weeks). Late HDN in breastfed infant occurs with a prevalence of about 20 per 100,000 live births when no neonatal prophylaxis is given. Parenteral (1 mg) K1 prevents late HDN and single or repeated doses of oral vitamin K reduces the incidence but does not eliminate all late HDN. The optimal (cost, feasibility, effective) mode of neonatal prophylaxis remains to be determined.

Topics: Adult; Age Factors; Child; Humans; Infant, Newborn; Public Health; Vitamin K; Vitamin K Deficiency

Several publications during the past 10-15 years report on the identification of acarboxyprothrombin (PIVKA II) in a varying proportion of examined newborn and babies (1.9 to 81.5%). These findings prove that the relevant infants were suffering from vitamin K deficiency. Hence, the researchers recommend to continue the prophylactic administration of Vitamin K to newborn. Another argument in favour of vitamin K prophylaxis is supplied by the results of epidemiological studies on the frequency of haemorrhages in newborn and babies caused by vitamin K deficiency. In respect of avoidance of haemorrhages, a single intramuscular injection of vitamin K appears to be the safest mode of application, but repeated peroral administration seems to be practically equally effective. The very frequently performed intramuscular injection of vitamin K is criticised not only because of possible local complications but also because of the greatly enhanced vitamin K concentrations in the blood after the injection. This enhanced concentration is accused of being responsible for the increased risk of malignant tumour growth in those babies who received vitamin K via the i.m. route, compared with the children who had not been given any injection or to whom vitamin K had been administered orally. For this reason vitamin K prophylaxis should be effected in newborn via the oral route (repeated administration), whereas the i.m. route should be an exception. Recommendations to this effect are already on record.

Topics: Dose-Response Relationship, Drug; Drug Administration Schedule; Hemorrhagic Disorders; Humans; Infant, Newborn; Prothrombin Time; Vitamin K; Vitamin K Deficiency

Fat-soluble vitamin deficiency is known to result in various complications that may be prevented if the problem is recognized and managed appropriately. In infants and children with chronic cholestasis, replacement therapy of the fat-soluble vitamins, vitamins A, D, E, and K, may prove extremely difficult because low concentrations of intraluminal bile acids lead to malabsorption of these compounds and other fat-soluble substances. Recent progress in the use of a water-soluble form of vitamin E, d-alpha-tocopheryl polyethylene glycol-1000 succinate, has enabled correction of vitamin E-deficiency states in these patients. It has also allowed for the admixture and coadministration of other fat-soluble vitamins and compounds in d-alpha-tocopheryl polyethylene glycol-1000 succinate to enhance their absorption. For managing vitamin K deficiency, similar success has been achieved using a vitamin K compound solubilized in glycocholate and lecithin. Vitamin A deficiency has been implicated in the higher incidence of childhood mortality and morbidity in Third World countries. Increased risk of childhood cancer has recently been associated with intramuscular injection of vitamin K to newborns. Finally, it is worth noting that among the pediatric population, exclusively breastfed infants, in general, are at risk for hypovitaminosis D, and at even greater risk in the absence of adequate exposure to sunlight or when the maternal diet is not sufficient to provide for vitamin D requirements.

Topics: Breast Feeding; Child; Humans; Infant; Vitamin A; Vitamin D Deficiency; Vitamin E Deficiency; Vitamin K; Vitamin K Deficiency

Vitamin K has several biological functions in which the major role is a cofactor for gamma-carboxylation of glutamate residues in Gla proteins, such as, several coagulant and anticoagulant proteins for blood clotting. This enzymatic process can be wholly dissolved. If adequate amounts of vitamin K are absent or anticoagulant drugs are administered, this process will be incomplete and abnormal proteins will appear in the blood. Recently, it was found that this carboxylation is blocked by the antibiotics having the N-methyltetrazolethiol group. These antibiotics inhibit vitamin K epoxide reductase, stop the recycling of vitamin K and cause vitamin K deficiency. Vitamin K is also necessary for biosynthesis of osteocalcin, which is a important protein in the normal function of the bone.

Topics: Animals; Female; Humans; Infant; Male; Vitamin K; Vitamin K Deficiency

This article reviews our current knowledge of the assessment of vitamin K status in the human infant, where a deficiency state has been described. Laboratory measures for the functional assessment of vitamin K-dependent coagulation factors as well as the quantitative assay for vitamin K1 (phylloquinone) are reviewed. In addition, four different methods of measuring abnormal prothrombin, a protein induced by vitamin K absence (PIVKA-II), and its use in clinical pediatrics are discussed. Finally, additional methods are briefly described for assessing vitamin K status, including serum osteocalcin, urinary excretion of gamma-carboxyglutamic acid, and deficiencies of the enzymes necessary for the regeneration of phylloquinone in the so-called vitamin K cycle.

Topics: Antibodies, Monoclonal; Biomarkers; Female; Humans; Immunoelectrophoresis; Infant; Infant, Newborn; Osteocalcin; Pregnancy; Protein Precursors; Prothrombin; Vitamin K; Vitamin K Deficiency

Topics: Animals; Anti-Bacterial Agents; Humans; Hypoprothrombinemias; Risk Factors; Vitamin K; Vitamin K Deficiency

Topics: Cost-Benefit Analysis; Germany; Humans; Infant, Newborn; Public Health; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Vitamin K is a substrate for a liver microsomal enzyme that catalyzes the conversion of specific glutamyl residues to gamma-carboxyglutamyl residues in a limited number of proteins. These include the vitamin K-dependent clotting factors: prothrombin (factor II), factor VII, factor IX, and factor X. In the absence of vitamin K, nonfunctional clotting factors are synthesized and hemorrhage can result. A Recommended Dietary Allowance of 1 micrograms/kg body weight has been established for vitamin K. Advances in analytic techniques and more sensitive clotting factor assays will make it possible to define the human requirement for this vitamin more accurately. A limited amount of data on the vitamin K content of foods is now available and reasonable estimates of intake can be calculated. Green leafy vegetables constitute the major source of vitamin K in the diet.

Topics: Food Analysis; Hemorrhage; Humans; Microsomes, Liver; Molecular Structure; Vitamin K; Vitamin K Deficiency

Topics: Administration, Oral; Animals; Anticoagulants; Calcium; Coumarins; Humans; Vitamin K; Vitamin K Deficiency

Topics: Amino Acid Sequence; Humans; Infant, Newborn; Molecular Sequence Data; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Administration, Oral; Age Factors; Breast Feeding; Evaluation Studies as Topic; Humans; Infant, Newborn; Injections, Intramuscular; Prothrombin Time; Risk Factors; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Humans; Infant, Newborn; Proteins; Vitamin K; Vitamin K Deficiency

Topics: Humans; Vitamin K; Vitamin K Deficiency

Topics: Humans; Infant, Newborn; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Biomarkers; Breast Feeding; Humans; Infant, Newborn; Nervous System Diseases; Protein Precursors; Prothrombin; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Age Factors; Humans; Infant; Infant Food; Infant Nutritional Physiological Phenomena; Infant, Newborn; Vitamin K; Vitamin K Deficiency

The incidence of hemorrhagic disease of the newborn (HDNB) can be expected to increase in Canada as breast-feeding becomes more popular. There are three clinical patterns of hemorrhagic disease: early HDNB (usually related to maternal drug ingestion), classic HDNB (related to breast-feeding) and late hemorrhagic disease of infancy (related to the combination of breast-feeding and diseases that cause fat malabsorption). Despite the knowledge that the disease can virtually be prevented by the administration of vitamin K, not all newborns are being routinely considered for such treatment. The Canadian Paediatric Society has made several recommendations: (a) women who take drugs that interfere with vitamin K1 metabolism should receive oral doses of vitamin K1 daily for a minimum of 2 weeks before expected delivery; (b) all healthy term infants should receive a single dose of vitamin K1, orally or intramuscularly, within 6 hours after birth; (c) all other newborns, including preterm, low-birthweight and sick infants, should receive a single intramuscular dose of vitamin K1 within 6 hours after birth; and (d) infants at high risk for secondary late-onset hemorrhagic disease due to fat malabsorption should receive vitamin K1 orally every day or intramuscularly once a month.

Topics: Administration, Oral; Breast Feeding; Humans; Infant, Newborn; Injections, Intramuscular; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Vitamin K catalyzes the post-translational carboxylation of coagulation proteins C, S, and factors II, VII, XI, and X. Detection of the noncarboxylated forms allows an indirect and specific measure of the vitamin K deficiency found in early, classic, and late hemorrhagic disease of the newborn (HDN), malabsorption syndromes, and drug related (warfarin, anticonvulsants, and antibiotics) states. Idiopathic late HDN (CNS bleeding) occurs in exclusively breast-fed infants and is prevented by appropriate parenteral and oral vitamin K prophylaxis given at birth. All newborn infants and older infants with malabsorption syndromes should receive prophylactic vitamin K.

Topics: Child; Humans; Infant; Infant, Newborn; Male; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Avitaminosis; Chemical Phenomena; Chemistry; Humans; Metabolism, Inborn Errors; Nutritional Requirements; Vitamin A; Vitamin A Deficiency; Vitamin D; Vitamin D Deficiency; Vitamin E; Vitamin E Deficiency; Vitamin K; Vitamin K Deficiency; Vitamins

Topics: Antihypertensive Agents; Blood Coagulation Disorders; Cerebral Hemorrhage; Erythroblastosis, Fetal; Ethamsylate; Female; Humans; Hypertension; Immunoglobulins; Infant, Newborn; Phenobarbital; Plasmapheresis; Pregnancy; Rho(D) Immune Globulin; Vitamin K; Vitamin K Deficiency

Since the discovery of gamma-carboxyglutamic acid a decade ago, great progress has been made in advancing our knowledge of the function and metabolism of vitamin K. The distribution of this new amino acid in proteins of diverse origin and the presence of the vitamin K-dependent carboxylase in diverse tissues have emphasized the widespread significance in biology of a new triad: vitamin K, Gla, and calcium. New knowledge has been obtained on the importance of the utilization and reutilization of vitamin K, whose body pools are extremely low for a fat-soluble vitamin, for the posttranslational carboxylation of peptide-bound glutamate residues in the vitamin K-dependent proteins. The regulation of the activation of the vitamin K-vitamin K-epoxide cycle by drugs and nutrients appears to be the key to controlling the synthesis of vitamin K-dependent proteins, eight of which are involved in blood coagulation. The purification of the vitamin K-dependent gamma-glutamyl carboxylase has turned out to be a more formidable task than anyone had imagined. Many of the questions about its complicated mechanism, utilizing as it does four substrates (KH2, O2, CO2, and a Glu-containing peptide), cannot be answered until the enzyme is homogeneous. Basically, the vitamin K-dependent carboxylase system consists of a specialized microsomal electron transport system coupled to a carbon dioxide fixation. The reaction does not require ATP but apparently utilizes the energy of vitamin KH2 oxidation to perform the chemical work required in Gla synthesis. Why a quinone is employed in this system when other mechanisms exist for CO2 fixation is still mysterious unless the whole process goes by one electron transport. Whether the final CO2 addition to the gamma-methylene group of glutamic acid is a radical reaction is unsettled. Since this enzyme is an intrinsic membrane-bound protein, the scientific attack on its structure and function is at one of the present frontiers of molecular biology. A view of the synthesis of vitamin K-dependent proteins in the RER is shown in Figure 9. Finally, the nutritional requirements for vitamin K in humans are unknown. An unknown fraction of vitamin K in humans is derived from menaquinone biosynthesis in the intestinal flora. Contributions from diet and biosynthesis have not yet been quantitated. Sensitive HPLC methods for measuring plasma phylloquinone are now available, and related methods for measuring long-chain menaquinones can be developed.

Topics: 4-Hydroxycoumarins; Amino Acid Sequence; Animals; Carbon-Carbon Ligases; DNA; DNA, Recombinant; Electron Transport; Genetic Variation; Humans; Immunologic Techniques; Intestinal Absorption; Kinetics; Ligases; Microsomes, Liver; Mixed Function Oxygenases; Nutritional Requirements; Peptides; Protein Binding; Protein Precursors; Protein Sorting Signals; Prothrombin; Quinone Reductases; RNA, Messenger; Salicylates; Tissue Distribution; Vitamin A; Vitamin E; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Vitamin K Epoxide Reductases

Much has been learned in the past 10 years about the mechanism of action of coumarin anticoagulants and the role of vitamin K in the production of functional clotting factors. This paper reviews the mechanism for post-ribosomal modification of precursor proteins into functional clotting factors, the therapeutic uses of vitamin K, pharmacologic and therapeutic uses of vitamin K antagonists, and the current means of testing for vitamin K antagonism. In addition, information concerning newly discovered vitamin K-dependent proteins in other tissues and pathologic processing is discussed.

Topics: 1-Carboxyglutamic Acid; Animals; Anticoagulants; Calcium-Binding Proteins; History, 19th Century; History, 20th Century; Humans; Infant, Newborn; Liver; Protein Precursors; Prothrombin; Rodenticides; United States; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Adult; Animals; Blood Coagulation Factors; Drug Interactions; Humans; Male; Vitamin E; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Warfarin

Topics: Breast Feeding; Cerebral Hemorrhage; Child; Child, Preschool; Factor IX; Humans; Hypoprothrombinemias; Infant; Infant, Newborn; Infant, Newborn, Diseases; Liver Function Tests; Prothrombin; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

In summary, in this review on the function of vitamin K in post-translational modification of precursor proteins by carboxylation of certain glutamyl residues, I have tried to cover in particular the recent work on the reaction, the enzymes involved and the mechanisms being considered. In doing this I have also considered vitamin K, its discovery, its functional form and the possible relation of its metabolism to the carboxylation reaction. Equally the various vitamin K-dependent gla-containing proteins currently known have been described. The carboxylation of synthetic small molecule exogenous substrates and the synthesis and metabolism of the products of carboxylation are of great help in studying the reaction. Structural specificity of vitamin K analogs in vivo and in vitro has been compared and the use of various antagonists in vivo and in vitro considered in attempts to gain an understanding of the overall reaction. The reactions subsequent to carboxylation, e.g., the activation of prothrombin to thrombin via serine proteases and the related activation of the other vitamin K-dependent proteins have not been considered in this review. The review has not covered prothrombin or other vitamin K-dependent protein isolation, nor the determination of these proteins. As the vitamin K-dependent protein carboxylation story has developed over the past six years, a number of reviews have been written which help in keeping up with the various aspects of the field as it has expanded. These reviews refer to many of the papers I have had to eliminate due to space limitations. They are referenced as 469-489. The review is in no sense comprehensive and many papers have been missed or only mentioned. I have tried to concentrate on the more recent work and, thus, much of the very fine work of the 1940's on vitamin K chemistry is hardly mentioned. Some redundancy has been built into the organization of the review so that a reader can obtain a reasonable view of any one section without having to search the whole review for all possible relevant information on any particular part of the field.

Topics: Animals; Binding Sites; Blood Proteins; Carboxy-Lyases; Chemical Phenomena; Chemistry; In Vitro Techniques; Microsomes, Liver; Oxidation-Reduction; Protein Precursors; Prothrombin; Rats; Solubility; Structure-Activity Relationship; Vitamin K; Vitamin K Deficiency

Topics: Alcoholism; alpha-Tocopherol; Animals; Calcifediol; Factor VII; Humans; Hydroxycholecalciferols; Intestinal Absorption; Liver Diseases, Alcoholic; Prothrombin Time; Tocopherols; Vitamin D; Vitamin D Deficiency; Vitamin E; Vitamin E Deficiency; Vitamin K; Vitamin K 1; Vitamin K Deficiency

A new class of proteins has emerged, the so-called vitamin K-dependent calcium binding proteins, which are uniquely characterized by the presence of alpha-carboxyglutamic acid residues. These proteins have been identified in a variety of tissues and body fluids. The specialized nature of calcium binding by Gla residues promotes protein phospholipid interaction, which is important not only in blood coagulation but in many tissue processes involving calcium metabolism. What role other than the blood coagulation mechanism the vitamin K reaction may play in diseases in children is still unclear.

Topics: Blood Coagulation Factors; Calcium-Binding Proteins; Carbon-Carbon Ligases; Female; Humans; Infant, Newborn; Ligases; Milk, Human; Osteocalcin; Prothrombin; Vitamin E; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: 1-Carboxyglutamic Acid; Animals; Blood Coagulation; Calcium; Carboxylic Acids; Cattle; Factor IX; Factor VII; Factor X; Glycoproteins; Humans; Liver; Microsomes; Models, Biological; Phospholipids; Prothrombin; Rats; Thrombin; Vitamin K; Vitamin K Deficiency

Vitamin K receives less dietary attention and fewer assays in foods than other fat-soluble vitamins. It is widely distributed in foods, usually at low concentrations. The human requirement is small. Intestinal bacteria synthesize vitamin K, which presumably helps provide the metabolic requirements for vitamin K. An RDA for vitamin K has not been published, but infants fed milk-substitute formulas risk vitamin K deficiency and it is recommended that those formulas contain supplemental vitamin K. Vitamin K in foods includes phylloquinone (K1) found in plants and several menaquinones (K2) found in animals and synthesized by microorganisms. Many vitamin K methods were developed primarily to identify forms present and determine their relative bioactivities. Until recently bioassays with chicks were the only practical methods to determine vitamin K content of foods. Various physicochemical methods have been developed to determine vitamins K in pure solutions, concentrates, and pharmaceuticals. Because of low concentrations of vitamin K in foods and the extensive purifications of extracts required, there has been only limited use of physicochemical methods, such as column chromatography, thin-layer chromatography, and high-performance liquid chromatography, with foods; the latter method perhaps offers the greatest possibilities for further development.

Topics: Animals; Biological Assay; Chemical Phenomena; Chemistry; Chickens; Chromatography; Chromatography, Gas; Chromatography, High Pressure Liquid; Chromatography, Paper; Chromatography, Thin Layer; Food Analysis; Humans; Prothrombin Time; Spectrophotometry; Terminology as Topic; Vitamin K; Vitamin K Deficiency

Topics: Animals; Epoxy Compounds; Microsomes, Liver; Mitochondria, Liver; Mixed Function Oxygenases; Oxidation-Reduction; Prothrombin; Rats; Vitamin K; Vitamin K Deficiency

Topics: 4-Hydroxycoumarins; Animals; Blood Coagulation; Coumarins; Electron Transport; Glutamates; History, 20th Century; Humans; Microsomes, Liver; Protein Precursors; Prothrombin; Tricarboxylic Acids; Vitamin K; Vitamin K Deficiency

Topics: Administration, Oral; Animals; Anticoagulants; Blood Coagulation; Blood Coagulation Factors; Blood Proteins; Clofibrate; Coumarins; Dicumarol; Disulfiram; Ethyl Biscoumacetate; Female; Heparin; Intestinal Absorption; Liver; Phenylbutazone; Protein Binding; Prothrombin; Prothrombin Time; Rabbits; Rats; Salicylates; Sulfonamides; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Animals; Anticoagulants; Barbiturates; Blood Coagulation; Blood Coagulation Factors; Cholestyramine Resin; Clofibrate; Disulfiram; Diuretics; Dogs; Drug Interactions; Heparin; Humans; In Vitro Techniques; Intestinal Absorption; Kinetics; Liver Diseases; Phenylbutazone; Protein Binding; Prothrombin Time; Rats; Receptors, Drug; Salicylates; Serum Albumin; Time Factors; Vitamin K; Vitamin K Deficiency

Topics: Amino Acid Sequence; Animals; Cycloheximide; Humans; Microsomes, Liver; Models, Chemical; Molecular Weight; Peptide Fragments; Protein Precursors; Prothrombin; Vitamin K; Vitamin K Deficiency

Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Lactation; Lipids; Male; Nutritional Requirements; Pregnancy; Vitamin A; Vitamin A Deficiency; Vitamin D; Vitamin D Deficiency; Vitamin E; Vitamin E Deficiency; Vitamin K; Vitamin K Deficiency

Topics: Amino Acids; Animals; Cycloheximide; Enzyme Precursors; Liver; Microsomes, Liver; Models, Chemical; Prothrombin; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Adult; Ascorbic Acid; Flavonoids; Hemorrhage; Hemostasis; Humans; Male; Prothrombin; Vitamin K; Vitamin K Deficiency; Vitamins

Topics: Animals; Calcium; Cattle; Coumarins; Cross Reactions; Enzyme Activation; Enzyme Precursors; Ethers, Cyclic; Humans; Hypoprothrombinemias; Liver; Microsomes, Liver; Protein Binding; Prothrombin; Rats; Snakes; Venoms; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Animals; Breast Feeding; Cattle; Diet; Female; Humans; Hypoprothrombinemias; Infant Food; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Newborn, Diseases; Milk; Milk, Human; Nutritional Requirements; Pregnancy; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Anticoagulants; Biopsy; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Drug Resistance; Drug Synergism; Factor IX; Factor VII; Factor X; Fibrinolysis; Humans; Liver; Liver Diseases; Prothrombin; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Animals; Barium Sulfate; Blood Proteins; Chromatography; Electrophoresis, Polyacrylamide Gel; Male; Prothrombin; Rats; Tritium; Vitamin K; Vitamin K Deficiency

Topics: Factor IX; Factor V; Factor VII; Factor X; Humans; Hypoprothrombinemias; Infant, Newborn; Methods; Prothrombin Time; Vitamin K; Vitamin K Deficiency

Topics: Animals; Carbon Isotopes; Chickens; Leucine; Liver; Protein Biosynthesis; Prothrombin; Rats; RNA, Messenger; Vitamin K; Vitamin K Deficiency

Topics: Animals; Avitaminosis; Bacteria; Blood Coagulation; Cats; Cattle; Dogs; Electron Transport; Guinea Pigs; Humans; Intestinal Absorption; Light; Lipids; Methods; Mice; Nutritional Requirements; Oxidative Phosphorylation; Plants; Quinones; Rabbits; Rats; Ubiquinone; Viruses; Vitamin K; Vitamin K Deficiency

Topics: Adult; Aged; Animals; Anti-Bacterial Agents; Blood Coagulation; Humans; Infant; Infant, Newborn; Intestines; Parenteral Nutrition; Rats; Vitamin K; Vitamin K Deficiency

Topics: Child; Humans; Vitamin K; Vitamin K Deficiency

Topics: Animals; Diet; Haplorhini; Humans; Rats; Research; Vitamin K; Vitamin K Deficiency

Vitamin K antagonists (VKAs), although commonly used to reduce thromboembolic risk in atrial fibrillation, have been incriminated as probable cause of accelerated vascular calcification (VC) in patients on hemodialysis. Functional vitamin K deficiency may further contribute to their susceptibility for VC. We investigated the effect of vitamin K status on VC progression in 132 patients on hemodialysis with atrial fibrillation treated with VKAs or qualifying for anticoagulation.. Patients were randomized to VKAs with target INR 2-3, rivaroxaban 10 mg daily, or rivaroxaban 10 mg daily plus vitamin K2 2000. Baseline dp-ucMGP was severely elevated in all groups. Initiation or continuation of VKAs further increased dp-ucMGP, whereas levels decreased in the rivaroxaban group and to a larger extent in the rivaroxaban+vitamin K2 group, but remained nevertheless elevated. Changes in coronary artery, thoracic aorta, and cardiac valve calcium scores and pulse wave velocity were not significantly different among the treatment arms. All cause death, stroke, and cardiovascular event rates were similar between the groups. Bleeding outcomes were not significantly different, except for a lower number of life-threatening and major bleeding episodes in the rivaroxaban arms versus the VKA arm.. Withdrawal of VKAs and high-dose vitamin K2 improve vitamin K status in patients on hemodialysis, but have no significant favorable effect on VC progression. Severe bleeding complications may be lower with rivaroxaban than with VKAs.

Topics: Aged; Aged, 80 and over; Antifibrinolytic Agents; Atrial Fibrillation; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Humans; Male; Prospective Studies; Renal Dialysis; Rivaroxaban; Stroke; Vascular Calcification; Vitamin K; Vitamin K 2; Vitamin K Deficiency

Kidney transplant recipients (KTRs) experience substantial survival benefit compared with dialysis patients. However, their mortality and graft failure risk remain high. KTRs are often low in micronutrient status, including vitamins D and K. We investigated the association of both vitamins D and K status, and vitamin D treatment with all-cause mortality and death-censored graft failure.. We studied 461 KTRs from a single-centre study at median 6.1 years after transplantation. At baseline, vitamins D and K concentrations were measured by 25-hydroxyvitamin D [25(OH)D] and dephosphorylated uncarboxylated matrix gla protein (dp-ucMGP) and patients were categorized into: 25(OH)D <50/≥50 nmol/L and median dp-ucMGP <1057/≥1057 pmol/L.. Mean age was 52 ± 12 years, and 122 KTRs (26%) had low vitamins D and K status. During median 9.8 years follow-up, 128 patients (28%) died and 48 (10%) developed death-censored graft failure. Low vitamins D and K status was associated with 2.33 (1.26-4.30) [hazard ratio (95% confidence interval)] increased mortality risk and 3.25 (1.17-9.08) increased graft failure risk compared with KTR with 25(OH)D ≥50 nmol/L and dp-ucMGP <1057 pmol/L. Dp-ucMGP was strongly associated with mortality (per 500 pmol/L increase): 1.41 (1.08-1.41) for vitamin D treatment versus no treatment 1.07 (0.97-1.18), and graft failure 1.71 (1.17-2.49) for vitamin D treatment versus 1.19 (1.05-1.36) no treatment, P-interaction <0.07 for vitamin D treatment (n = 44).. Combined vitamins D and K deficiency are highly prevalent and are associated with increased mortality and graft failure risk compared with high vitamins D and K status. Low vitamin K status was strongly associated with an increased risk of premature mortality and graft failure for patients treated with vitamin D versus no vitamin D treatment.

Topics: Female; Graft Rejection; Graft Survival; Humans; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Prognosis; Prospective Studies; Survival Rate; Vitamin D; Vitamin K; Vitamin K Deficiency

To compare the prevalence of vitamin K deficiency after intramuscular vitamin K or no treatment in neonates with sepsis on prolonged (>7 days) antibiotic therapy.. Open label randomized controlled trial.. Level 3 Neonatal Intensive Care Unit (NICU).. Neonates with first episode of sepsis on antibiotics for ≥7 days were included. Neonates with clinical bleeding, vitamin K prior to start of antibiotic therapy (except the birth dose), cholestasis or prenatally diagnosed bleeding disorder were excluded.. Randomized to receive 1 mg vitamin K (n=41) or no vitamin K (n=39) on the 7th day of antibiotic therapy.. Vitamin K deficiency defined as Protein Induced by Vitamin K Absence (PIVKA-II) >>2 ng/mL after 7 ± 2 days of enrolment.. The prevalence of vitamin K deficiency was 100% (n=80) at enrolment and it remained 100% even after 7 ± 2 days of enrolment in both the groups.. Neonates receiving prolonged antibiotics have universal biochemical vitamin K deficiency despite vitamin K administration on 7th day of antibiotic therapy.

Topics: Anti-Bacterial Agents; Female; Follow-Up Studies; Humans; Infant, Newborn; Injections, Intramuscular; Intensive Care Units, Neonatal; Intensive Care, Neonatal; Lemierre Syndrome; Male; Prevalence; Treatment Outcome; Vitamin K; Vitamin K Deficiency; Vitamins

Vitamin K (VK)-dependent γ-glutamate carboxylation and serine phosphorylation activate matrix Gla protein (MGP) to a potent locally acting inhibitor of calcification. Nephrolithiasis represents a process of unwanted calcification associated with substantial mortality and high recurrence rates. We hypothesized that the risk of nephrolithiasis increases with VK shortage, as exemplified by higher plasma levels of desphospho-uncarboxylated MGP (dp-ucMGP).. In 1748 randomly recruited Flemish individuals (51.1% women; mean age 46.8 years), we determined dp-ucMGP and the prevalence of nephrolithiasis at baseline (April 1996-February 2015) and its incidence during follow-up until March 2016. We estimated the multivariable-adjusted relative risk associated with the doubling of dp-ucMGP, using logistic or Cox regression. We did a Mendelian randomization analysis using four MGP genotypes as instrumental variables.. With adjustments applied for sex, age and 24-h urinary volume and calcium excretion, the odds of having prevalent nephrolithiasis [n = 144 (8.2%)] associated with dp-ucMGP was 1.31 [95% confidence interval (CI) 1.04-1.64; P = 0.022]. dp-ucMGP levels were associated (P ≤ 0.001) with MGP variants rs2098435, rs4236 and rs2430692. In the Mendelian analysis, the causal odds ratio was 3.82 (95% CI 1.15-12.7; P = 0.029). The incidence of nephrolithiasis over 12.0 years (median) was 37 cases (0.2%). With similar adjustments as before, the hazard ratio in relation to dp-ucMGP was 2.48 (95% CI 1.71-3.61; P < 0.001). Additional adjustment for a nephrolithiasis propensity score produced consistent results.. Higher levels of inactive dp-ucMGP may be causally associated with the risk of nephrolithiasis. Whether or not VK deficiency plays a role in these observations remains to be firmly established.

Topics: Adult; Belgium; Biomarkers; Calcium-Binding Proteins; Extracellular Matrix Proteins; Female; Genotype; Humans; Incidence; Male; Matrix Gla Protein; Mendelian Randomization Analysis; Middle Aged; Nephrolithiasis; Phosphorylation; Prognosis; Vitamin K; Vitamin K Deficiency; Young Adult

Subclinical vitamin K deficiency is prevalent among renal transplant recipients and is associated with an increased risk of cardiovascular disease. However, the association between vitamin K supplementation and improvement of arterial stiffness has not been explored in the renal transplant population. The KING trial (vitamin K2 In reNal Graft) is a single-arm study that evaluated the association between the change in vitamin K status and indices of arterial stiffness following 8 weeks of menaquinone-7 (vitamin K2) supplementation (360 μg once daily) among renal transplant recipients (n = 60). Arterial stiffness was measured using carotid-femoral pulse wave velocity (cfPWV). Subclinical vitamin K deficiency was defined as plasma concentration of dephosphorylated-uncarboxylated matrix Gla protein (dp-ucMGP) >500 pmol/L.At baseline, 53.3% of the study subjects had subclinical vitamin K deficiency. Supplementation was associated with a 14.2% reduction in mean cfPWV at 8 weeks (cfPWV pre-vitamin K2 = 9.8 ± 2.2 m/s vs. cfPWV post-vitamin K2 = 8.4 ± 1.5 m/s; P < .001). Mean dp-ucMGP concentrations were also significantly reduced by 55.1% following menaquinone-7 supplementation with a reduction in the prevalence of subclinical deficiency by 40% (P = .001). When controlled for age, durations of hemodialysis and transplantation, and the change in 24-hour mean arterial pressure, the improvement in arterial stiffness was independently associated with the reduction in dp-ucMGP concentration (P = .014).Among renal transplant recipients with stable graft function, vitamin K2 supplementation was associated with improvement in subclinical vitamin K deficiency and arterial stiffness. (Clinicaltrials.gov: NCT02517580).

Topics: Adult; Biomarkers; Calcium-Binding Proteins; Dietary Supplements; Extracellular Matrix Proteins; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Matrix Gla Protein; Middle Aged; Pilot Projects; Prevalence; Prospective Studies; Pulse Wave Analysis; Renal Dialysis; Treatment Outcome; Vascular Calcification; Vascular Stiffness; Vitamin K; Vitamin K 2; Vitamin K Deficiency; Vitamins

To determine prophylactic role of single dose of vitamin K in prevention of antibiotic induced hypoprothrombinemia.. This prospective comparative study included critically ill children in age group 2 mo to 12 y, admitted to a tertiary care hospital in India, likely to receive prolonged antibiotic therapy. One hundred twenty children, 60 in each group (A & B) were enrolled in the study. Patient allocation was done on alternate basis. Group A children received prophylactic vitamin K while group B did not. Baseline coagulation studies and other investigations were done in all children. Coagulation studies were repeated on day 10 and day 14 of antibiotic therapy and in between if required clinically. Children who developed deranged INR were given therapeutic vitamin K. If deranged INR returns to normal at 12 h of vitamin K administration then it indirectly confirms vitamin K deficiency. Analysis was done by fisher's t test and chi square test.. In children on prolonged antibiotic therapy, vitamin K deficiency was a common problem (15%). It was common in male sex, severe grade of protein energy malnutrition (PEM), N-methylthiotetrazole (NMTT) group containing antibiotics use and duration of antibiotic more than 10 d. It was same in children whether they received or did not receive prophylactic vitamin K on day 1 of antibiotic therapy (95% CI; p value 0.79).. Vitamin K deficiency is common problem in patients on prolonged antibiotic therapy. There is no role of single dose of prophylactic vitamin K in preventing antibiotic induced hypoprothrombinemia.

Topics: Anti-Bacterial Agents; Blood Coagulation; Chemoprevention; Child; Child, Preschool; Critical Illness; Drug Administration Schedule; Drug Monitoring; Female; Hemostatics; Humans; Hypoprothrombinemias; Infant; International Normalized Ratio; Male; Treatment Outcome; Vitamin K; Vitamin K Deficiency

Vitamin K's recommended dietary allowance (RDA) is based on the hepatic requirement for clotting factor synthesis, but substantial concentrations of undercarboxylated extra-hepatic Gla-proteins are found in the circulation of non-supplemented individuals. This suggests that vitamin K intake above the RDA is required for an optimal extra-hepatic vitamin K status. Circulating uncarboxylated osteocalcin (ucOC) and desphospho-uncarboxylated matrix Gla-protein (dp-ucMGP) are considered markers of the vitamin K status in bone and the vasculature, respectively. We measured these markers in 896 samples of healthy volunteers and defined target groups for vitamin K supplementation based on increased levels indicative of tissue-specific vitamin K deficiency. We studied the response to vitamin K supplements at different states of vitamin K deficiency by measuring the circulating dp-ucMGP level in samples from two short-term trials on menaquinone-7 (MK-7, vitamin K2) supplementation in 42 children and 68 adults. Children had high ucOC levels (3.4-96.9 ng ml(-1)); other age groups had values in the range of 1.5-5.0 ng ml(-1). From the age of 40 years, dp-ucMGP levels gradually increased. Children and adults with more pronounced vitamin K deficiency gave the highest responses to MK-7 supplementation. Children and adults above 40 years showed the largest tissue-specific vitamin deficiency and accordingly may benefit from MK-7 supplementation to improve their extra-hepatic vitamin K status.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Calcium-Binding Proteins; Child; Child, Preschool; Dietary Supplements; Extracellular Matrix Proteins; Female; Healthy Volunteers; Humans; Male; Matrix Gla Protein; Middle Aged; Osteocalcin; Vitamin K; Vitamin K Deficiency; Young Adult

Osteocalcin (OC) is a vitamin K-dependent protein found in bone and in circulation. High serum γ-carboxylated OC reflects a high, and high uncarboxylated OC (ucOC) reflects a low vitamin K status. A revolutionary hypothesis is that ucOC acts as a hormone improving glucose handling and reducing fat mass. The objective was to test the logical extrapolation of the ucOC hormone hypothesis to humans that elevated ucOC is associated with higher body weight, BMI and fat mass. In a cross-sectional analysis, the associations of vitamin K status with circulating adiponectin and body composition were investigated in 244 postmenopausal women (study I). The effects of vitamin K treatment on adiponectin, body weight and BMI were investigated in archived samples from forty-two young men and women who received varying doses of menaquinone-7 during 12 weeks (study II) and from a cohort of 164 postmenopausal women who participated in a 3-year placebo-controlled trial on 45 mg menaquinone-4 (MK-4) (study III). No association was found between vitamin K status and circulating adiponectin before or after vitamin K supplementation. A higher carboxylation of OC was significantly correlated with lower body weight, BMI and fat mass of the trunk. Women taking MK-4 maintained their baseline body weight and BMI, whereas women taking placebo showed significant increases in both indices. These findings demonstrate that a high vitamin K status of bone has no effect on circulating adiponectin in healthy people and long-term vitamin K supplementation does not increase weight in healthy postmenopausal women.

Topics: Adiponectin; Adiposity; Adult; Aged; Body Composition; Body Weight; Cohort Studies; Cross-Sectional Studies; Dietary Supplements; Double-Blind Method; Female; Humans; Male; Middle Aged; Osteocalcin; Postmenopause; Premenopause; Retrospective Studies; Severity of Illness Index; Vitamin K; Vitamin K Deficiency; Young Adult

As the vitamin K content of human milk is low and the newborn infant's stores of vitamin K are small, vitamin K deficiency with hemorrhage in the newborn is a worldwide problem. Proteins Induced by Vitamin K Absence (PIVKA-II) are the inactive under-γ-carboxylated forms of vitamin K-dependent clotting factors and they could be useful in predicting subclinical vitamin K deficiency (VKD).. To demonstrate that PIVKA-II are earlier markers of subclinical VKD than Prothrombin time (PT) in exclusively breast-fed newborns.. A prospective, controlled, randomized study, including 53 term newborns receiving vitamin K prophylaxis (0.5 mg i.m.) at birth, was performed. At 30 days newborns were divided into three groups (G) receiving respectively: 25 μg/die of vitamin K (G I), 12 μg/die (G II) or placebo (G III). PIVKA-II and PT were measured on 30th and 90th days of life.. G III and GII showed a significant increase in PIVKA-II from 30 to 90 days of life respectively from 2.6 to 4.7 (p = 0.001) and from 2.3 to 3.5 (p < 0.001). No significant changes were found in GI. PT showed no significant changes among groups.. PT is a less sensitive marker than PIVKA II. Oral supplementation with 25 μg/die avoids an increase of PIVKA-II. Despite increased PIVKA-II do not mean an impending occurrence of bleeding, they highlight a subclinical VKD and its relative risk.

Topics: Asymptomatic Diseases; Biomarkers; Dietary Supplements; Early Diagnosis; Fetal Blood; Humans; Infant; Infant, Newborn; Protein Precursors; Prothrombin; Prothrombin Time; Term Birth; Time Factors; Vitamin K; Vitamin K Deficiency

Vitamin K is required for the carboxylation of Gla-proteins in the liver (coagulation factors) and extra-hepatic tissues, such as bone (osteocalcin, OC), and arterial wall (matrix Gla-protein, MGP). Although the coagulation factors are essentially fully carboxylated under normal conditions, 10-40 % of OC and MGP remains undercarboxylated. We were therefore interested to study the dose-response effects of extra intake of menaquinones on the carboxylation of the extra-hepatic Gla-proteins. A total of forty-two healthy Dutch men and women aged between 18 and 45 years were randomised into seven groups to receive: placebo capsules or menaquinone-7 (MK-7) capsules at a daily dose of 10, 20, 45, 90, 180 or 360 μg. Circulating uncarboxylated OC (ucOC), carboxylated OC (cOC) and desphospho-uncarboxylated MGP were measured by ELISA. The ucOC:cOC ratio was calculated from circulating ucOC and cOC values. Endogenous thrombin potential and peak height were determined by calibrated automated thrombography. To increase the statistical power, we collapsed the treatment groups into three dosage groups: placebo, low-dose supplementation (doses below RDA, Commission Directive 2008/100/EC), and high-dose supplementation (doses around RDA, Commission Directive 2008/100/EC). MK-7 supplementation at doses in the order of the RDA (Commission Directive 2008/100/EC) increased the carboxylation of circulating OC and MGP. No adverse effects on thrombin generation were observed. Extra MK-7 intake at nutritional doses around the RDA (Commission Directive 2008/100/EC) improved the carboxylation of the extra-hepatic vitamin K-dependent proteins. Whether this improvement contributes to public health, i.e. increasing the protection against age-related diseases needs further investigation in specifically designed intervention trials.

Topics: Adult; Algorithms; Blood Coagulation; Blood Coagulation Tests; Decarboxylation; Dietary Supplements; Double-Blind Method; Female; Hemostatics; Humans; Male; Middle Aged; Netherlands; Nutritional Status; Osteocalcin; Pilot Projects; Vitamin K; Vitamin K 2; Vitamin K Deficiency; Young Adult

Preterm infants may be at particular risk from either inadequate or excessive vitamin K prophylaxis. Our goal was to assess vitamin K status and metabolism in preterm infants after 3 regimens of prophylaxis.. Infants <32 weeks' gestation were randomized to receive 0.5 mg (control) or 0.2 mg of vitamin K1 intramuscularly or 0.2 mg intravenously after delivery. Primary outcome measures were serum vitamin K1, its epoxide metabolite (vitamin K1 2,3-epoxide), and undercarboxylated prothrombin assessed at birth, 5 days, and after 2 weeks of full enteral feeds. Secondary outcome measures included prothrombin time and factor II concentrations.. On day 5, serum vitamin K1 concentrations in the 3 groups ranged widely (2.9-388.0 ng/mL) but were consistently higher than the adult range (0.15-1.55 ng/mL). Presence of vitamin K1 2,3-epoxide on day 5 was strongly associated with higher vitamin K1 bolus doses. Vitamin K1 2,3-epoxide was detected in 7 of 29 and 4 of 29 infants from the groups that received 0.5 mg intramuscularly and 0.2 mg intravenously, respectively, but in none of 32 infants from group that received 0.2 mg intramuscularly. After 2 weeks of full enteral feeding, serum vitamin K1 was lower in the infants who received 0.2 mg intravenously compared with the infants in the control group. Three infants from the 0.2-mg groups had undetectable serum vitamin K1 as early as the third postnatal week but without any evidence of even mild functional deficiency, as shown by their normal undercarboxylated prothrombin concentrations.. Vitamin K1 prophylaxis with 0.2 mg administered intramuscularly maintained adequate vitamin K status of preterm infants until a median age of 25 postnatal days and did not cause early vitamin K1 2,3-epoxide accumulation. In contrast, 0.2 mg administered intravenously and 0.5 mg administered intramuscularly led to vitamin K1 2,3-epoxide accumulation, possibly indicating overload of the immature liver. To protect against late vitamin K1 deficiency bleeding, breastfed preterm infants given a 0.2-mg dose of prophylaxis should receive additional supplementation when feeding has been established.

Topics: Female; Humans; Infant, Newborn; Infant, Premature, Diseases; Male; Vitamin K; Vitamin K Deficiency; Vitamins

The relation between different doses of vitamin K supplementation, several bone markers, and PIVKA-II concentrations in cystic fibrosis (CF) patients compared to controls was evaluated. Results suggest that a increased vitamin K intake may have significant health benefits for children with CF.

Topics: Biomarkers; Cystic Fibrosis; Dose-Response Relationship, Drug; Humans; Osteocalcin; Protein Precursors; Prothrombin; Vitamin K; Vitamin K Deficiency

The present study is aimed at evaluating the efficacy of maternal vitamin K2 supplementation on the vitamin K status of newborn infants using the measurement of des-gamma-carboxyprothrombin (PIVKA-II [protein induced by vitamin K absence]) and the hepaplastin test (HPT). PIVKA-II and HPT were measured at the 1st month of age in two groups: 31 infants with maternal vitamin K supplementation (15 mg/d Menatetrenone since the 14th day after parturition) (group 1) and 46 without maternal supplementation (group 2). All infants received vitamin K2 syrup twice within the 1st week of life. The PIVKA-II levels of 31 infants (group 1) were 23.6 mAU/mL (standard deviation [SD] 5.8), showing extremely low levels, and close to healthy adult levels, with a smaller deviation than what was seen in group 2. The levels of the 46 infants in group 2 were 27.8 (SD 16.0). This does not differ significantly from group 1, but a small number of infants showed a modestly high level in PIVKA-II. There also was no significant difference between the two groups in the HPT. These data would indicate that maternal vitamin K supplementation can maintain the vitamin K status throughout the late neonatal period and prevent an onset of vitamin K-deficient hemorrhage.

Topics: Biomarkers; Breast Feeding; Female; Hemorrhage; Humans; Indicators and Reagents; Infant, Newborn; Organic Chemicals; Protein Precursors; Prothrombin; Vitamin K; Vitamin K 2; Vitamin K Deficiency

Subjects taking a hydrogen pump blocking agent (omeprazole) develop bacterial overgrowth of the small intestine. We tested the hypothesis that this bacterial overgrowth produces menaquinones, which would meet the vitamin requirement in situations of vitamin K deficiency. In a crossover-type design, 13 healthy volunteers eating a phylloquinone-restricted diet for 35 d were randomly assigned to take omeprazole during the first period of study or starting on day 15 until the end of the study. Coagulation times, serum osteocalcin [total osteocalcin and undercarboxylated osteocalcin (ucOC)], plasma phylloquinone, urinary gamma-carboxyglutamic acid, and plasma undercarboxylated prothrombin (PIVKA-II) were measured. Plasma phylloquinone concentrations declined 82% with dietary phylloquinone restriction (P < 0.05) and were not significantly different in the period when the diet was combined with omeprazole treatment (P > 0.05). The mean value for PIVKA-II during the phylloquinone-restricted diet significantly increased 5.7-fold from baseline (P < 0.05); however, the combination of omeprazole treatment and the phylloquinone-restricted diet significantly reduced PIVKA-II values by 21% (P < 0.05) compared with the diet period alone. There were no alterations in total or percentage ucOC concentrations during the phylloquinone-restricted diet or during the period of diet plus omeprazole treatment. Our data support the hypothesis that bacterial overgrowth results in the synthesis and absorption of menaquinones. These menaquinones contribute to vitamin K nutriture during dietary phylloquinone restriction, but not enough to restore normal vitamin K status.

Topics: 1-Carboxyglutamic Acid; Achlorhydria; Adult; Aged; Bacteria; Biomarkers; Cross-Over Studies; Diet; Drug Interactions; Humans; Intestine, Small; Middle Aged; Omeprazole; Osteocalcin; Protein Precursors; Prothrombin; Vitamin K; Vitamin K 1; Vitamin K Deficiency

Significant reduction in bone mineral density (BMD) occurs in stroke patients on the hemiplegic and contralateral sides, correlating with the degree of paralysis and vitamin D and K deficiency due to malnutrition, and increasing the risk of hip fracture. We evaluated the efficacy of vitamin K2 (menatetrenone: menaquinone-4; MK-4) in maintaining BMD by comparing serum biochemical indices of bone metabolism between treated and untreated patients. In a random and prospective study, of 108 hemiplegic patients following stroke, 54 received 45 mg menatetrenone daily (MK-4 group, n = 54) for 12 months, and the remaining 54 (untreatment group) did not. Nine patients excluded from the study. The BMD in the second metacarpals and serum indices of bone metabolism were determined. BMD on the hemiplegic side increased by 4.3% in the MK-4 group and decreased by 4.7% in the untreated group (p < 0.0001), while BMD on the intact side decreased by 0.9% in the MK-4 group and by 2.7% in the untreated group (p < 0.0001). At baseline, patients of both groups showed vitamin D and K1 deficiencies, high serum levels of ionized calcium, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), and low levels of parathyroid hormones (PTH) and bone Gla proteins (BGP), indicating that immobilization-induced hypercalcemia inhibits renal synthesis of 1, 25-dihydroxyvitamin D (1, 25-[OH]2D) and compensatory PTH secretion. Both vitamins K1 and K2 increased by 97.6% and 666.9%, respectively, in the MK-4 group. Correspondingly, a significant increase in BGP and decreases in both ICTP and calcium were observed in the MK-4 group, in association with a simultaneous increase in both PTH and 1, 25-[OH]2D. One patient in the untreated group suffered from a hip fracture, compared with none in the MK-4 group. The treatment with MK-4 can increase the BMD of disused and vitamin D- and K-deficient hemiplegic bone by increasing the vitamin K concentration, and it also can decrease calcium levels through inhibition of bone resorption, resulting in an increase in 1, 25-[OH]2D concentration.

Topics: Aged; Biomarkers; Bone Density; Bone Diseases, Metabolic; Cerebrovascular Disorders; Female; Hemiplegia; Hemostatics; Humans; Male; Metacarpus; Middle Aged; Prospective Studies; Vitamin D Deficiency; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

To compare a new oral preparation of vitamin K1 (Konakion MM) containing lecithin and glycocholic acid with a standard intramuscular (IM) preparation during the first 8 weeks of life in exclusively breast fed infants.. Infants were randomised at birth to the IM group (1 mg vitamin K) or the oral group (2 mg given at birth and repeated at 7 and 30 days of life). Prothrombin time (INR), plasma vitamin K1, and PIVKA II (undercarboxylated prothrombin) were monitored at 14, 30, and 56 days of age.. Seventy nine infants were randomised to the oral group and 77 to the IM group. Sixty seven infants in each group completed eight weeks of the study. Prothrombin times did not differ between the two groups. Mean (SD) plasma vitamin K1 values (in ng/ml) decreased in both groups over time, but were higher in the oral group at 14 and 56 days: 2.0 (1.6) v 1.3 (1.1) at 14 days; 0.5 (0.3) v 0.5 (0.7) at 30 days; and 0.5 (0.8) v 0.2 (0.2) at 56 days of life. PIVKA II was raised (> or = 0.1 AU/ml) in cord blood in 47% of the infants. By 14 days, only one infant in each group had a raised PIVKA II value and both of these initially had high concentrations of PIVKA II in cord blood. At 30 days, there were no raised PIVKA II values. At 56 days, there were no raised PIVKA II values in the oral group, although three infants in the IM group had raised values.. Plasma vitamin K concentrations were at least equal or significantly higher in babies given oral vitamin K supplements compared with IM treated babies at the time points measured. Through the first 8 weeks of life, multiple doses of the new oral preparation maintain haemostasis and vitamin K status in breast fed infants at least equal to that of the intramuscular preparation.

Topics: Administration, Oral; Biomarkers; Breast Feeding; Female; Fetal Blood; Humans; Infant, Newborn; Injections, Intramuscular; Male; Protein Precursors; Prothrombin; Prothrombin Time; Vitamin K; Vitamin K Deficiency

There is consensus that late vitamin K deficiency bleeding (VKDB) should be prevented by vitamin K prophylaxis. One single dose of 1 mg vitamin K1 is effective if given i.m. or s.c., but not if given orally. Repeated oral doses might be as effective as the parenteral dose but the optimal dose regimen remains to be established. Different oral dose schedules are presently used in different countries. In Australia, Germany, The Netherlands and Switzerland active surveillance data on late VKDB were collected in a similar manner and failure rates compared. Identical case definitions were used. There were three basic strategies for oral and one for parenteral vitamin K prophylaxis for healthy newborns in the four countries: (1) daily supplementation of low dose vitamin K (25 micrograms) for breast-fed infants (The Netherlands); (2) 3 x 1 mg orally [Australia (January 1993-March 1994) and Germany (December 1992-December 1994)]; (3) 1 mg vitamin K i.m. (Australia since March 1994); and (4) 2 x 2 mg vitamin K (new mixed micellar preparation) (Switzerland). The respective failure rates per 100,000 live births (including cases given all recommended doses and those given incomplete prophylaxis) were for strategy: (1) 0.2 (0-1.3) in The Netherlands; (2) 2.3 (95% CI 1.6-3.4) in Germany and 2.5 (1.1-4.8) in Australia (oral prophylaxis); (3) Australia (i.m. prophylaxis) 0 (0-0.9); and (4) 3.6 (0.7-10.6) in Switzerland. The failure rates for complete prophylaxis only were: strategy (1) 0 (0-0.7) in The Netherlands; (2) 1.8 (1.1-2.8) in Germany and 1.5 (0.5-3.6) in Australia; (3) Australia (i.m.) 0 (0-0.9); and (4) 1.2 (0-6.5) in Switzerland.. The Australian data confirm that three oral doses of 1 mg vitamin K are less effective than i.m. vitamin K prophylaxis. A daily low oral dose of 25 micrograms vitamin K1 following an initial oral dose of 1 mg after birth for exclusively breast-fed infants may be as effective as parenteral vitamin K prophylaxis. The effectiveness of the "mixed-micellar" preparation of vitamin K1 needs further study.

Topics: Administration, Oral; Drug Administration Schedule; Hemorrhagic Disorders; Humans; Infant; Infant, Newborn; Vitamin K; Vitamin K Deficiency

Topics: Administration, Oral; Biomarkers; Birth Weight; Breast Feeding; Female; Follow-Up Studies; Gestational Age; Humans; Infant, Newborn; Injections, Intramuscular; Male; Pilot Projects; Protein Precursors; Prothrombin; Prothrombin Time; Vitamin K; Vitamin K Deficiency

Topics: Bone Marrow Transplantation; Drug-Related Side Effects and Adverse Reactions; Humans; Vitamin K; Vitamin K Deficiency

Intramuscular administration of vitamin K for prophylaxis against hemorrhagic disease of the newborn has the disadvantage of increased cost, pain, anxiety to parents and risk of transmission of infection. Oral route is a better alternative. Oral absorption of vitamin K has been shown to be equally good using special oral preparations. However, this preparation is not available in India. A prospective study was carried out on 51 full term, healthy breastfed newborns to evaluate if the injectable water soluble preparation of vitamin K (menadione sodium bisulphite) could be as effective. Fourteen babies received 1 mg vitamin K intramuscularly, 24 received 2 mg vitamin K orally while 13 controls did not receive vitamin K at birth. PIVKA-II levels were measured in cord blood and at 72-78 hours of age in all babies as a marker of vitamin K deficiency. The overall PIVKA-II prevalence in cord blood was 64.7%. At 72-78 hours, PIVKA-II was present in 50% of babies in IM group, 58.3% of babies in oral group and in 76.9% of babies in 'no vitamin K' group (p > 0.05). The PIVKA-II levels decreased or did not change at 72-78 hours in 91.6% of babies in oral group versus 92.8% of babies in IM group (p > 0.05). On the other hand, PIVKA-II levels increased in 30.7% of babies who did not receive vitamin K as against in 7.8% of babies receiving vitamin K in either form (p < 0.05). Hence, vitamin K prophylaxis is required for all newborns at birth and injectable vitamin K (menadione sodium bisulphite) given orally to term healthy babies is effective in preventing vitamin K deficiency state.

Topics: Administration, Oral; Biomarkers; Female; Fetal Blood; Humans; Infant, Newborn; Injections, Intramuscular; Male; Prospective Studies; Protein Precursors; Prothrombin; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

The influence of breast or formula feeding together with that of a single supplementation of vitamin K1 at birth, on the vitamin K1 level and vitamin K-dependent clotting factors were studied in 65 breast and 15 formula fed infants. All breast fed newborns without supplementation (n = 25) had very low serum vitamin K1 at weeks 1 and 6. Oral vitamin K supplementation (n = 22) or i.m. (n = 18) at birth resulted in high serum levels at week 1, while at week 6 the effect had disappeared. Formula fed infants had vitamin K1 values within the normal adult range at all study points. The low serum levels of vitamin K1 were not associated with haemorrhagic disorders or coagulation abnormalities. The mean values of vitamin K1 in maternal sera at weeks 1 and 6 were 2.3 nmol/l and 1.8 nmol/l and in breast milk 2.7 nmol/l and 2.0 nmol/l respectively. No correlation existed between the values in breast milk and maternal serum. To maintain serum levels of vitamin K1 within the adult physiological range, repeated administration of low doses is needed in breast fed newborns beyond 1 week of age.

Topics: Breast Feeding; Cross-Sectional Studies; Double-Blind Method; Female; Humans; Infant Food; Infant, Newborn; Longitudinal Studies; Milk, Human; Mothers; Protein C; Prothrombin; Vitamin K; Vitamin K Deficiency

The null hypothesis of this study is that extra vitamin K administered to pregnant women on a regimen of enzyme-inducing anticonvulsant therapy will not decrease the frequency of symptoms of vitamin K deficiency in their neonates.. A multicenter case-control study was performed on 16 pregnant women on anticonvulsant therapy who received 10 mg of vitamin K1 daily from 36 weeks of pregnancy onward. Concentrations of PIVKA-II (protein induced by vitamin K absence for factor II) and of vitamin K1 were determined in cord blood and compared with those in 20 controls.. In none of 17 cord samples was PIVKA-II detectable, compared with 13 of 20 in controls (chi 2, p < 0.001). Median cord vitamin K1 level was 530 pg/ml compared with below detection limit in most controls.. Antenatal vitamin K1 treatment decreases the frequency of vitamin K deficiency in neonates of mothers on anticonvulsant therapy.

Topics: Anticonvulsants; Biomarkers; Case-Control Studies; Epilepsy; Female; Fetal Blood; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Protein Precursors; Prothrombin; Reference Values; Vitamin K; Vitamin K Deficiency

A randomised clinical trial was conducted to establish the effects of oral and intramuscular administration of vitamin K at birth on plasma concentrations of vitamin K1, proteins induced by vitamin K absence (PIVKA-II), and clotting factors. Two groups of about 165 healthy breast fed infants who received at random 1 mg vitamin K1 orally or intramuscularly after birth were studied at 2 weeks and 1 and 3 months of age. Although vitamin K1 concentrations were statistically significantly higher in the intramuscular group, blood coagulability, activities of factors VII and X and PIVKA-II concentrations did not reveal any difference between the two groups. At 2 weeks of age vitamin K1 concentrations were raised compared with reported unsupplemented concentrations and no PIVKA-II was detectable. At 3 months vitamin K1 concentrations were back at unsupplemented values and PIVKA-II was detectable in 11.5% of infants. Therefore, a repeated oral prophylaxis will be necessary to completely prevent (biochemical) vitamin K deficiency beyond the age of 1 month.

Topics: Administration, Oral; Biomarkers; Blood Coagulation; Breast Feeding; Female; Humans; Infant; Infant, Newborn; Injections, Intramuscular; Male; Protein Precursors; Prothrombin; Vitamin K; Vitamin K 1; Vitamin K Deficiency

Plasma vitamin K concentrations and prothrombin coagulation activity were determined in 26 normal adults who had received daily beta-carotene supplementation (0, 15, 30, or 60 mg) for six months. Neither plasma vitamin K nor coagulation activity were significantly decreased at any supplementation level. Thus, chronic beta-carotene supplementation, even at high daily doses, is not expected to result in clinical vitamin K deficiency. The data suggest separate mechanisms for intestinal absorption of beta-carotene and vitamin K.

Topics: Aged; beta Carotene; Carotenoids; Clinical Trials as Topic; Diet; Double-Blind Method; Drug Administration Schedule; Female; Humans; Intestinal Absorption; Male; Middle Aged; Prothrombin Time; Vitamin K; Vitamin K Deficiency

Vitamin K deficiency has been reported in patients who were treated with antibiotics and placed on poor diets after surgery. High-performance liquid chromatography (HPLC) was used to study the influence of dietary intake on vitamin K concentrations in surgical patients (n = 22). Plasma phylloquinone decreased rapidly from 1.19 +/- 0.16 to 0.47 +/- 0.12 nmol/L (means +/- SEM, n = 11) on a low-phylloquinone diet and from 1.16 +/- 0.12 to 0.36 +/- 0.07 nmol/L (n = 11) by postoperative fasting. A small amount of phylloquinone and a large amount of menaquinone were found in liver tissue. Phylloquinone concentration was 28.0 +/- 4.3 pmol/g liver (wet weight) on the standard diet (n = 7) whereas it was 6.8 +/- 1.1 pmol/g on the low-phylloquinone diet after 3 d (n = 8). Because phylloquinone is rapidly depleted by fasting, it may be difficult to prevent vitamin K deficiency by dietary phylloquinone alone during long-term fasting after surgery.

Topics: Adult; Aged; Chromatography, High Pressure Liquid; Fasting; Female; Humans; Intraoperative Period; Liver; Male; Middle Aged; Postoperative Period; Preoperative Care; Vitamin K; Vitamin K Deficiency

In 34 cancer patients with 40 neutropenic febrile episodes requiring broad-spectrum antimicrobial therapy, detailed dietary assessments revealed that deficient and severely deficient phylloquinone intakes (less than or equal to 70 and less than or equal to 25 micrograms/d) were identified during 88% and 38% of all days recorded, respectively. Serum phylloquinone levels and serial prothrombin times (PT) drawn in a similar group of 32 patients revealed that an elevated PT (greater than or equal to 2 s beyond control) was significantly associated (p less than 0.01) with a serum phylloquinone level of less than 4.4 nmol/L. Patients on antimicrobial regimens that suppressed menaquinone-producing intestinal microflora and that contained an N-methylthiotetrazole (NMTT) moiety had an elevated PT significantly more often than did patients receiving antimicrobial agents that preserved the microflora and contained no NMTT moiety (3 of 10 vs 10 of 11, respectively; p = 0.02 Fisher's exact). These data suggest that these patients have a profound deficiency of oral vitamin K intake that may be further augmented by antimicrobial therapy.

Topics: Agranulocytosis; Anti-Bacterial Agents; Diet; Fever; Humans; Hypoprothrombinemias; Intestines; Neoplasms; Neutropenia; Prothrombin Time; Vitamin K; Vitamin K 1; Vitamin K Deficiency

Vitamin K is required for the maintenance of normal hemostatic function. Ten college-aged male subjects chose diets restricted in vitamin K content for 40 d. Median phylloquinone intakes based on analysis of food composites dropped from 82 micrograms/d during the prestudy period to 40 and 32 micrograms/d at d 9 and 27 of dietary restriction, respectively. Serum phylloquinone concentrations fell from a mean of 0.87 to 0.46 ng/mL during a 21-d period of vitamin K restriction. Supplementation with 50 micrograms phylloquinone/d for 12 d increased serum phylloquinone to 0.56 ng/mL, and supplementation with 500 micrograms phylloquinone/d increased serum phylloquinone to 1.66 ng/mL. Vitamin K restriction resulted in alterations in a functional clotting assay that detects undercarboxylated prothrombin species in plasma and in a decrease in urinary gamma-carboxyglutamic acid. Supplementation with either 50 or 500 micrograms of phylloquinone restored both these indices to near normal values. These data are consistent with a human dietary vitamin K requirement of approximately 1 microgram/kg body wt/d.

Topics: Adult; Blood Coagulation; Humans; Male; Time Factors; Vitamin K; Vitamin K 1; Vitamin K Deficiency

Vitamin K acts a cofactor for the gamma-carboxylation of several proteins in the coagulation cascade. The clinical spectrum of vitamin K deficiency (VKD) can be asymptomatic to a significant bleeding. VKD is classically seen in newborns. However, this can manifest later in patients with risks such as sub-optimal nutrition, fat malabsorption, medications including antibiotics. A 17-year-old male with spinal muscular atrophy (SMA) Type 1, tracheostomy with ventilator dependent, gastrostomy tube feeding was seen by the gastroenterologist following treatment for small intestinal bacterial overgrowth (SIBO). Investigations showed coagulopathy following which he was transferred to the Pediatric ICU. Labs revealed prothrombin time (PT) 114 s [Normal 9.4-12.5 s], INR (International normalized ratio) 12.6 [Normal < 1.1] and partial thromboplastin time (PTT) 90 s [Normal 25.1-36.5 s]. Mixing studies and coagulation assays were consistent with VKD (low Factor VII and Factor IX with normal Factor V). His home blenderized feeding regimen met the caloric requirement but not the adequate intake (AI) values for vitamin K and other minerals. He received intravenous vitamin K (phytonadione) for five consecutive days with resolution of the coagulopathy (PT 13.2 s, PTT 37.1 s, INR 1.2). The patient was discharged on enteral vitamin K and additional supplements following dietary review by a nutritionist. Clinicians should be cognizant of VKD in patients on blenderized tube feeds which may not meet the adequate intake (AI) goals. In patients who are not receiving nutritionally complete formulas or receiving inadequate volumes, it is important to monitor macro and micronutrients.

Topics: Adolescent; Child; Dietary Supplements; Enteral Nutrition; Humans; Infant, Newborn; Male; Vitamin K; Vitamin K 1; Vitamin K Deficiency

Vitamin K is an essential fat-soluble vitamin for the human body and its functions, such as promoting blood coagulation, bone health and preventing atherosclerosis, have attracted increasing attention. However, there is no recognized indicator and corresponding reference range for evaluating vitamin K status of different populations at present. The aim of this study is to establish a reference range for vitamin K evaluating indicators in healthy women of childbearing age in China.. The population sample in this study was from the Chinese Adult Chronic Disease and Nutrition Surveillance (CACDNS) 2015-2017. A total of 631 healthy women of childbearing age (18-49 years) were included using a series of strict inclusion and exclusion criteria. The concentrations of VK1, MK-4 and MK-7 in serum were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The other commonly-reported indicators evaluating vitamin K nutritional status, including undercarboxylated osteocalcin (ucOC), osteocalcin (OC), matrix Gla protein (MGP), desphosphorylated undercaboxylated MGP (dp-ucMGP) and protein induced by vitamin K absence II (PIVKA-II), were measured by enzyme-linked immunosorbent assay (ELISA). The reference range was obtained by calculating the 2.5% to 97.5% interval of the vitamin K evaluating indicators in the reference population.. The reference ranges of VK1, MK-4 and MK-7 in serum were 0.21-3.07 ng/mL, 0.02-0.24 ng/mL and 0.12-3.54 ng/mL, respectively. The reference ranges of ucOC, %ucOC, dp-ucMGP and PIVKA-II were 1.09-2.51 ng/mL, 5.80-22.78%, 2.69-5.88 ng/mL and 3.98-8.40 ng/mL, respectively. The cut-off values that can be used to evaluate subclinical vitamin K deficiency were as follows: VK1 < 0.21 ng/mL, MK-7 < 0.12 ng/mL, ucOC > 2.51 ng/mL, %ucOC > 22.78%, dp-ucMGP > 5.88 ng/mL and PIVKA-II > 8.40 ng/mL.. The reference range of VK1, MK-4, MK-7 and vitamin K-related indicators for healthy women of childbearing age established in this study could be used to assess the nutritional and health status of this population.

Topics: Adolescent; Adult; Biomarkers; Chromatography, Liquid; East Asian People; Female; Humans; Middle Aged; Osteocalcin; Reference Values; Tandem Mass Spectrometry; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency; Vitamins; Young Adult

Nutritional support is essential for patients with severe motor and intellectual disabilities (SMID) to ensure the smooth provision of medical care. These patients often require long-term tube feeding with enteral formulas, potentially leading to deficiencies in vitamins and trace elements. Additionally, frequent antibiotic use for infections often disrupts gut microbiota, inhibiting vitamin K2 production by intestinal bacteria. We assessed the serum protein induced by vitamin K absence or antagonists-II (PIVKA-II) and undercarboxylated osteocalcin (ucOC) levels to assess the vitamin K status in 20 patients with SMID (median age: 44.1 years, 11 men and 9 women) undergoing long-term tube feeding for durations ranging from 3 to 31 years. Thirteen (65%) and nine (45%) patients had elevated PIVKA-II (<40 mAU/mL) and serum ucOC levels (reference value < 4.50 ng/mL), respectively. Dietary vitamin K1 intake did not differ between patients with and without elevated PIVKA-II levels. Vitamin K2 supplementation for 3 months decreased serum PIVKA-II levels near those within the reference range. Approximately half of the patients with SMID on tube feeding had subclinical vitamin K deficiency. Further studies are needed to ascertain if long-term vitamin K2 supplementation effectively prevents vitamin K deficiency-induced hypercoagulation, osteoporosis, and vascular calcification in patients with SMID.

Topics: Adult; Biomarkers; Dietary Supplements; Enteral Nutrition; Female; Humans; Intellectual Disability; Male; Osteocalcin; Prothrombin; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

Hyperphosphataemia is strongly associated with cardiovascular disease and mortality. Recently, phosphate binders (PBs), which are used to bind intestinal phosphate, have been shown to bind vitamin K, thereby potentially aggravating vitamin K deficiency. This vitamin K binding by PBs may offset the beneficial effects of phosphate reduction in reducing vascular calcification (VC). Here we assessed whether combining PBs with vitamin K2 supplementation inhibits VC.. We performed 3/4 nephrectomy in rats, after which warfarin was given for 3 weeks to induce vitamin K deficiency. Next, animals were fed a high phosphate diet in the presence of low or high vitamin K2 and were randomized to either control or one of four different PBs for 8 weeks. The primary outcome was the amount of thoracic and abdominal aorta VC measured by high-resolution micro-computed tomography (µCT). Vitamin K status was measured by plasma MK7 levels and immunohistochemically analysed in vasculature using uncarboxylated matrix Gla protein (ucMGP) specific antibodies.. The combination of a high vitamin K2 diet and PB treatment significantly reduced VC as measured by µCT for both the thoracic (P = 0.026) and abdominal aorta (P = 0.023), compared with MK7 or PB treatment alone. UcMGP stain was significantly more present in the low vitamin K2-treated groups in both the thoracic (P < 0.01) and abdominal aorta (P < 0.01) as compared with high vitamin K2-treated groups. Moreover, a high vitamin K diet and PBs led to reduced vascular oxidative stress.. In an animal model of kidney failure with vitamin K deficiency, neither PB therapy nor vitamin K2 supplementation alone prevented VC. However, the combination of high vitamin K2 with PB treatment significantly attenuated VC.

Topics: Animals; Calcium-Binding Proteins; Extracellular Matrix Proteins; Female; Male; Models, Animal; Phosphates; Rats; Renal Dialysis; Renal Insufficiency; Vascular Calcification; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency; X-Ray Microtomography

Chronic kidney disease (CKD) is accompanied with extensive cardiovascular calcification, in part correlating with functional vitamin K deficiency. Here, we sought to determine causes for vitamin K deficiency beyond reduced dietary intake. Initially, vitamin K uptake and distribution into circulating lipoproteins after a single administration of vitamin K1 plus K2 (menaquinone 4 and menaquinone 7, respectively) was determined in patients on dialysis therapy and healthy individuals. The patients incorporated very little menaquinone 7 but more menaquinone 4 into high density lipoprotein (HDL) and low-density lipoprotein particles than did healthy individuals. In contrast to healthy persons, HDL particles from the patients could not be spiked with menaquinone 7 in vitro and HDL uptake was diminished in osteoblasts. A reduced carboxylation activity (low vitamin K activity) of uremic HDL particles spiked with menaquinone 7 vs. that of controls was confirmed in a bioassay using human primary vascular smooth muscle cells. Kidney menaquinone 4 tissue levels were reduced in 5/6-nephrectomized versus sham-operated C57BL/6 mice after four weeks of a vitamin K rich diet. From the analyzed enzymes involved in vitamin K metabolism, kidney HMG-CoA reductase protein was reduced in both rats and patients with CKD. In a trial on the efficacy and safety of atorvastatin in 1051 patients with type 2 diabetes receiving dialysis therapy, no pronounced vitamin K deficiency was noted. However, the highest levels of PIVKA-II (biomarker of subclinical vitamin K deficiency) were noted when a statin was combined with a proton pump inhibitor. Thus, profound disturbances in lipoprotein mediated vitamin K transport and metabolism in uremia suggest that menaquinone 7 supplementation to patients on dialysis therapy has reduced efficacy.

Topics: Animals; Diabetes Mellitus, Type 2; Humans; Mice; Mice, Inbred C57BL; Rats; Renal Insufficiency, Chronic; Tissue Distribution; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

People with HIV (PWH) experience increased systemic inflammation and monocyte activation, leading to increased risk of cardiovascular events (death, stroke, and myocardial infarction) and higher coronary artery calcium scores (CACs). Vitamins D and K2 have significant anti-inflammatory effects; in addition, vitamin K2 is involved in preventing vascular calcifications in the general population. The roles of vitamins D and K in increased coronary calcifications in successfully treated PWH is less understood.. We prospectively recruited 237 PWH on antiretroviral treatment (ART) and 67 healthy controls. CACs were derived from noncontrast chest computed tomography (CT) and levels of 25-hydroxyvitamin D (vitamin D) and inactive vitamin K-dependent dephosphorylated-uncarboxylated matrix Gla protein (dp-uc MGP, marker of vitamin K deficiency) were measured in plasma during a fasting state. The relationship between inflammation markers, dp-uc MGP, and vitamin D on CACs were estimated using zero-inflated negative binomial regression. Adjusted models included 25(OH)D, MGP, sex, race, age, and markers of inflammation or monocyte activation.. Overall, controls had lower median age (45.8 vs. 48.8; P = 0.03), a larger proportion of female individuals (55.2 vs. 23.6%; P < 0.0001), and nonwhite (33.8 vs. 70%; P < 0.0001). Among PWH, less than 1% had detectable viral load and the median CD4+ cell count was 682 (IQR: 473.00-899.00). 62.17% of the participants had zero CACs and 51.32% were vitamin D-deficient (<20 ng/ml). There was no difference in detectable CACs (P = 0.19) or dp-uc MGP (P = 0.42) between PWH and controls. In adjusted models, PWH with nonzero CACs have three times greater expected CAC burden compared with controls. Every 1% increase in MGP (worse K status) decreases the probability of having CACs equal to zero by 21.33% (P = 0.01). Evidence suggests that the effects of 25(OH)D and MGP are inflammation-mediated, specifically through sVCAM, TNF-αRI, and TNF-αRII.. Vitamin K deficiency is a modifiable preventive factor against coronary calcification in PWH. Further research should determine whether vitamin K supplementation would reduce systemic inflammation, vascular calcification, and risk of cardiovascular events in PWH.

Topics: Biomarkers; Cardiovascular Diseases; Female; HIV Infections; Humans; Inflammation; Vascular Calcification; Vitamin D; Vitamin K; Vitamin K Deficiency; Vitamins

Fetal brain hemorrhage is rare. It is caused mainly by maternal trauma or fetal coagulation disorder, but in some cases, vitamin K deficiency may be the cause.. We describe the case of a pregnant woman with bowel obstruction who was susceptible to vitamin K deficiency due to oral diet restriction, decreased intestinal absorption, and limited intravenous vitamin K supplementation.. After 18 days of intermittent total parenteral nutrition, acute onset of severe fetal brain hemorrhage developed.. After acute onset of fetal brain hemorrhage, the patient underwent an emergency cesarean section at 25 + 3 weeks of gestation due to fetal non-reassuring fetal monitoring.. The Apgar score at birth was 0/0, and despite cardiopulmonary resuscitation, neonatal death was confirmed. After the baby was delivered, we checked the maternal upper abdominal cavity and found a massive adhesion in the small bowel to the abdominal wall near the liver and stomach with an adhesion band. The adhesion band, presumably a complication of previous hepatobiliary surgery, appeared to have caused small bowel obstruction. Adhesiolysis between the small bowel and abdominal wall was performed.. This case demonstrates that even relatively short-term total parenteral nutrition can cause severe fetal brain hemorrhage. Vitamin K supplementation is required for mothers who are expected to be vitamin K deficient, especially if they are on total parenteral nutrition for more than 3 weeks.

Topics: Adult; Cesarean Section; Female; Fetal Diseases; Humans; Infant, Newborn; Intestinal Obstruction; Intracranial Hemorrhages; Parenteral Nutrition, Total; Pregnancy; Vitamin K; Vitamin K Deficiency

Vascular calcification (VC) is highly prevalent in Chronic Kidney Disease (CKD) patients, progresses gradually with deterioration of kidney function and is a strong, independent predictor of cardiovascular (CV) mortality. Matrix Gla Protein (MGP), the most potent inhibitor of VC, requires vitamin K as a co-factor to become biologically active. Accumulating epidemiological data have associated vitamin K depletion with VC progression and CV outcomes. CKD patients are characterized by poor vitamin K status and at the same time, pronounced CV calcification. In early and advanced CKD, including end-stage kidney disease, exogenous supplementation of vitamin K (especially with menaquinone 7, its most bioavailable form) might decrease the inactive form of MGP (dephosphorylated, uncarboxylated MGP) and probably retard the progression or even reverse VC. Here, we focus and discuss the interventional human studies of vitamin K supplementation in CKD patients and suggest future directions in this area of interest.

Topics: Dietary Supplements; Female; Humans; Male; Renal Dialysis; Renal Insufficiency, Chronic; Vascular Calcification; Vitamin K; Vitamin K Deficiency

Vitamin K and its derivatives represent a complex of fat-soluble vitamins, playing a major role in the regulation of a large number of physiologic processes required for optimal homeostasis [...].

Topics: Chronic Disease; Foods, Specialized; Humans; Vitamin A; Vitamin D; Vitamin E; Vitamin K; Vitamin K Deficiency; Vitamins

BACKGROUND Cefmetazole (CMZ), containing an N-methyl-tetrazole-thiol (NMTT) side chain, is a therapeutic option for diverticulitis in Japan. Cephems containing an NMTT, a methyl-thiadiazol, and a thiadiazolethiol side chain are known to induce coagulation disorders. CASE REPORT A 76-year-old woman developed hypoprothrombinemia after receiving oral levofloxacin (LVFX) 250 mg q24h for 2 days followed by intravenous CMZ 2 g q8h for sigmoid diverticulitis. On day 5 of CMZ administration (after 12 doses in total), black stool was observed. On the following day (after 14 doses), prothrombin time (PT) prolongation was noted; PT and international normalized ratio (INR) were 37.1 s and 2.47, respectively. We diagnosed the patient with hypoprothrombinemia because of vitamin K deficiency caused by markedly elevated protein levels induced by vitamin K absence or antagonist-II on day 6 of CMZ administration. Intravenous vitamin K administration and CMZ cessation rapidly restored PT and led to the disappearance of black stool. CONCLUSIONS The causes of vitamin K deficiency were considered to be an impaired vitamin K cycle due to CMZ and decreased vitamin K intake because of malnutrition. These findings are consistent with CMZ's reported adverse effects. Decreased vitamin K production due to alterations in the gut bacterial flora by LVFX and CMZ was also postulated as a cause. If a bleeding tendency is noted during diverticulitis treatment with NMTT-containing cephems, switching to intravenous quinolones or carbapenems is recommended. It remains unclear how this reaction can be avoided; however, prudent monitoring of bleeding signs and PT-INR is recommended.

Topics: Aged; Anti-Bacterial Agents; Blood Coagulation Disorders; Cefmetazole; Diverticulitis; Female; Humans; Hypoprothrombinemias; Vitamin K; Vitamin K Deficiency

The development of coagulation disorders can be dangerous and fatal in the older people, especially those with multiple medical conditions. Vitamin K-dependent coagulation disorders are easily overlooked when anticoagulant drugs are not used and the patient shows no signs of bleeding.. We report a case of a 71-year-old male suffering from pulmonary infection with severe coagulation disorder without bleeding symptoms. He also had a history of Parkinson's disease, Alzheimer's disease and cardiac insufficiency. Coagulation tests were normal at the time of admission, prothrombin time (PT) is 13.9 (normal, 9.5-13.1) seconds and the activated partial thromboplastin time (APTT) is 30.2 (normal, 25.1-36.5) seconds. But it turned severely abnormal after 20 days (PT: 136.1 s, APTT: 54.8 s). However, no anticoagulants such as warfarin was used and no bleeding symptoms were observed. Subsequent mixing studies with normal plasma showed a decrease in prothrombin times. Vitamin K deficiency was thought to be the cause of coagulation disorders considering long-term antibiotic therapy, especially cephalosporins, inadequate diet and abnormal liver function. After supplementation with 20 mg of vitamin K, coagulation dysfunction was rescued the next day and serious consequences were effectively prevented.. Overall, timely vitamin K supplementation with antimicrobials that affect vitamin K metabolism requires clinician attention, especially in older patients who are multimorbid, frail or nutritionally compromised, and are admitted to hospital because of an infection that needs antimicrobial therapy are at risk of clotting disorders due to abnormal vitamin K metabolism secondary to altered gut flora, which can exacerbate existing nutritional deficiencies.

Topics: Aged; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Humans; Male; Pneumonia; Vitamin K; Vitamin K Deficiency

There is near-global consensus that all newborns be given parenteral vitamin K. To assess the prevalence of functional VK insufficiency in preterm infants based on elevated under-γ-carboxylated (Glu) species of Gla proteins, factor II (PIVKA-II), and osteocalcin (GluOC), synthesized by liver and bone, respectively.. Preterm infants who remain exclusively or predominantly human breastmilk-fed after neonatal unit discharge are at high risk of developing subclinical VK deficiency in early infancy. Routine postdischarge VK

Topics: Aftercare; Hemorrhage; Humans; Infant; Infant, Newborn; Infant, Premature; Milk, Human; Patient Discharge; Prospective Studies; Vitamin K; Vitamin K 1; Vitamin K Deficiency

Chronic kidney disease (CKD) commonly occurs with vitamin K (VK) deficiency and impaired bone mineralization. However, there are no data explaining the metabolism of endogenous VK and its role in bone mineralization in CKD. In this study, we measured serum levels of phylloquinone (VK1), menaquinone 4 and 7 (MK4, MK7), and VK-dependent proteins: osteocalcin, undercarboxylated osteocalcin (Glu-OC), and undercarboxylated matrix Gla protein (ucMGP). The carboxylated osteocalcin (Gla-OC), Glu-OC, and the expression of genes involved in VK cycle were determined in bone. The obtained results were juxtaposed with the bone mineral status of rats with CKD. The obtained results suggest that the reduced VK1 level observed in CKD rats may be caused by the accelerated conversion of VK1 to the form of menaquinones. The bone tissue possesses all enzymes, enabling the conversion of VK1 to menaquinones and VK recycling. However, in the course of CKD with hyperparathyroidism, the intensified osteoblastogenesis causes the generation of immature osteoblasts with impaired mineralization. The particular clinical significance seems to have a finding that serum osteocalcin and Glu-OC, commonly used biomarkers of VK deficiency, could be inappropriate in CKD conditions, whereas Gla-OC synthesized in bone appears to have an adverse impact on bone mineral status in this model.

Topics: Animals; Biomarkers; Bone and Bones; Minerals; Osteocalcin; Rats; Renal Insufficiency, Chronic; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

Systems genetics is key for integrating a large number of variants associated with diseases. Vitamin K (VK) is one of the scarcely studied disease conditions. In this work, we ascertained the differentially expressed genes (DEGs) and variants associated with individual subpopulations of VK disease phenotypes,

Topics: Biomarkers; Humans; Male; Prostatic Neoplasms; RNA, Long Noncoding; Vitamin K; Vitamin K Deficiency

Vitamin K, especially its K2 form, is considered to be a protective factor against developing vascular changes and bone lesions that are common complications in kidney transplant (KTx) recipients. There is a growing number of studies showing that KTx patients are at risk of vitamin K deficiency. The aim of this study was to evaluate the intake of vitamin K1 and K2 in the diet of patients in the late period after KTx. During a routine visit at one outpatient transplantation clinic in Central Europe, a diet survey questionnaire was filled in by 151 clinically stable KTx recipients and compared with medical history, anthropometric measurements and laboratory tests. Mean vitamin K1 intake was 120.9 ± 49 μg/day and vitamin K2 (MK, menaquinone) intake 28.69 ± 11.36 μg/day, including: MK-4: 25.9 ± 9.9 μg/day; MK-5: 0.1 ± 0.2 μg/day; MK-6: 0.2 ± 0.4 μg/day; MK-7: 0.2 ± 0.23 μg/day; MK-8: 1 ± 1.9 μg/day; MK-9: 0.9 ± 2.3 μg/day; and MK-10: 0.2 ± 0.5 μg/day. Our study showed that KTx recipients' diets contained adequate amounts of vitamin K1, whereas the intake of vitamin K2 seemed insufficient.

Topics: Diet; Humans; Kidney Transplantation; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

Vitamin K deficiency consistently associates with worse clinical outcome in COVID-19 patients. However, whether this is due to increased expenditure during inflammation or poor vitamin K status prior to infection remained unknown.. Dp-ucMGP levels of 128 individuals were measured for the post-MONICA study and were compared to SARS-CoV-2 PCR testing results.. Dp-ucMGP levels prior to COVID-19 infection were not significantly different comparing PCR-negative, PCR-positive and not hospitalized, and PCR-positive and hospitalized patients.. In this study, we demonstrate normal vitamin K status prior to infection in SARS-CoV-2 positive patients, supporting the theory of increased utilisation during disease.

Topics: Biomarkers; Calcium-Binding Proteins; COVID-19; Extracellular Matrix Proteins; Health Expenditures; Humans; SARS-CoV-2; Vitamin K; Vitamin K Deficiency

Topics: Humans; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Vitamin K dependent proteins (VKDP), such as hepatic coagulation factors and vascular matrix Gla protein (MGP), play key roles in maintaining physiological functions. Vitamin K deficiency results in inactive VKDP and is strongly linked to vascular calcification (VC), one of the major risk factors for cardiovascular morbidity and mortality. In this study we investigated how two vitamin K surrogate markers, dephosphorylated-undercarboxylated MGP (dp-ucMGP) and protein induced by vitamin K absence II (PIVKA-II), reflect vitamin K status in patients on hemodialysis or with calcific uremic arteriolopathy (CUA) and patients with atrial fibrillation or aortic valve stenosis. Through inter- and intra-cohort comparisons, we assessed the influence of vitamin K antagonist (VKA) use, vitamin K supplementation and disease etiology on vitamin K status, as well as the correlation between both markers. Overall, VKA therapy was associated with 8.5-fold higher PIVKA-II (0.25 to 2.03 AU/mL) and 3-fold higher dp-ucMGP (843 to 2642 pM) levels. In the absence of VKA use, non-renal patients with established VC have dp-ucMGP levels similar to controls (460 vs. 380 pM), while in HD and CUA patients, levels were strongly elevated (977 pM). Vitamin K supplementation significantly reduced dp-ucMGP levels within 12 months (440 to 221 pM). Overall, PIVKA-II and dp-ucMGP showed only weak correlation (r

Topics: 4-Hydroxycoumarins; Aortic Valve Stenosis; Atrial Fibrillation; Biomarkers; Calcium-Binding Proteins; Cardiovascular Diseases; Cohort Studies; Dietary Supplements; Extracellular Matrix Proteins; Female; Heart Disease Risk Factors; Humans; Indenes; Liver; Male; Matrix Gla Protein; Middle Aged; Nutritional Status; Protein Precursors; Prothrombin; Renal Dialysis; Uremia; Vascular Calcification; Vitamin K; Vitamin K Deficiency

We present a family who suffered recurrent sibling losses due to vitamin K deficiency bleed. The index child was asymptomatic at presentation, had normal clinical examination, and was investigated for coagulation disorders in view of previous 3 sibling losses as a result of intracranial hemorrhage. His investigations showed deranged coagulogram and clotting factors' assay. The baby was given vitamin K1 1 mg intramuscularly following which his coagulogram and clotting factors' assay returned to normal. The genetic analysis did not identify any inherited cause of bleeding tendency. The significant family history, exclusive breastfeeding, no diarrhea, failure to thrive or drug use, no prophylaxis with vitamin K at birth, recovery of clotting factors on vitamin K administration, and a corroborative molecular analysis confirmed diagnosis of vitamin K deficiency in the index child. This case gives a strong reminder not to miss birth dose of vitamin K in any neonate.

Topics: Antifibrinolytic Agents; Blood Coagulation; Humans; Infant; Infant, Newborn; Intracranial Hemorrhages; Male; Siblings; Vitamin K; Vitamin K Deficiency

To explore the association of both plasma vitamin D and K concentrations with all-cause mortality, cardiovascular mortality, and cardiovascular events in the general population.. We studied 4742 participants of the Prevention of REnal and Vascular ENd-Stage Disease (PREVEND) Study. At baseline, vitamin D and K status was determined by measurement of 25-hydroxyvitamin D [25(OH)D] and dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP), respectively. Patients were categorized into: 25(OH)D < 50 or ≥ 50 nmol/L and dp-ucMGP < 361 or ≥ 361 pmol/L with 25(OH)D > 75 nmol/L and dp-ucMGP < 361 pmol/L as reference. Cause of death was coded according to International Classification of Diseases 9&10 codes from the 2001-2003 examination until date of death/event or censoring date (January 1st, 2017).. Mean age was 52.6 ± 11.9 years and 2513 (53%) were female. During a median of 14.2 year follow-up, 620 participants died of which 142 were due to cardiovascular causes. Combined low vitamin D and K status was present in 970 participants (20%) and was associated with a greater risk of all-cause mortality compared to high vitamin D and high vitamin K status group (n = 1424) after adjusting for potential confounders: hazard ratio 1.46 (95% confidence intervals 1.12-1.90). We observed similar trends, albeit non-significant for cardiovascular mortality, and cardiovascular events: 1.42 (0.79-2.55), 1.28 (0.93-1.77), respectively.. Combined low vitamin D and K status are associated with increased all-cause mortality risk and possibly with cardiovascular mortality and cardiovascular events compared with adequate vitamin D and K status. Future studies should investigate the effect of combined vitamin D and K supplementation on clinical outcomes.

Topics: Adult; Calcium-Binding Proteins; Cardiovascular Diseases; Female; Humans; Male; Middle Aged; Prospective Studies; Risk Factors; Vitamin D; Vitamin K; Vitamin K Deficiency

Coronavirus disease 2019 (Covid-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2, exerts far-reaching effects on public health and socio-economic welfare. The majority of infected individuals have mild to moderate symptoms, but a significant proportion develops respiratory failure due to pneumonia. Thrombosis is another frequent manifestation of Covid-19 that contributes to poor outcomes. Vitamin K plays a crucial role in the activation of both pro- and anticlotting factors in the liver and the activation of extrahepatically synthesised protein S which seems to be important in local thrombosis prevention. However, the role of vitamin K extends beyond coagulation. Matrix Gla protein (MGP) is a vitamin K-dependent inhibitor of soft tissue calcification and elastic fibre degradation. Severe extrahepatic vitamin K insufficiency was recently demonstrated in Covid-19 patients, with high inactive MGP levels correlating with elastic fibre degradation rates. This suggests that insufficient vitamin K-dependent MGP activation leaves elastic fibres unprotected against SARS-CoV-2-induced proteolysis. In contrast to MGP, Covid-19 patients have normal levels of activated factor II, in line with previous observations that vitamin K is preferentially transported to the liver for activation of procoagulant factors. We therefore expect that vitamin K-dependent endothelial protein S activation is also compromised, which would be compatible with enhanced thrombogenicity. Taking these data together, we propose a mechanism of pneumonia-induced vitamin K depletion, leading to a decrease in activated MGP and protein S, aggravating pulmonary damage and coagulopathy, respectively. Intervention trials should be conducted to assess whether vitamin K administration plays a role in the prevention and treatment of severe Covid-19.

Topics: Calcium-Binding Proteins; COVID-19; Extracellular Matrix Proteins; Humans; Lung; Matrix Gla Protein; Protein S; SARS-CoV-2; Thromboembolism; Thrombosis; Vitamin K; Vitamin K Deficiency

Febrile seizure is the most common neurological disorder in childhood. The exact pathophysiology of febrile seizures is unknown. Recent studies showed the role of vitamin K in nonhematological and inflammatory disorders. This study aimed to investigate the serum vitamin K levels in children with febrile seizures.. To evaluate vitamin K levels in children with febrile seizures.. Prospective case-control study.. This multicenter study examined representative populations in 8 different cities in Turkey between April 1, 2018 and April 1, 2019. Blood samples were taken from all children at presentation. Vitamin K1, vitamin K2, tumor necrosis factor-alpha, interleukin 1 beta, and interleukin 6 levels were determined by enzyme-linked immunosorbent assay.. A total of 155 children were included in the study-84 children with febrile seizures and 71 children in febrile control group. Serum vitamin K1 and vitamin K2 levels were also higher in children with febrile seizures than in the controls. The results of statistical analysis showed that vitamin K1 and vitamin K2 levels were correlated with tumor necrosis factor-alpha, interleukin 1 beta, and interleukin 6 levels. The median vitamin K1 and vitamin K2 levels of children experiencing their first febrile seizure were higher than those in children with recurrent febrile seizures. Type of febrile seizure has no effect on serum vitamin K1 and vitamin K2 levels.. In children with febrile seizures, vitamin K levels are higher than those in the control group. These new findings may contribute to elucidating the etiopathogenesis of febrile seizures.

Topics: Adolescent; Adult; Case-Control Studies; Child; Child, Preschool; Female; Humans; Interleukin-1beta; Interleukin-6; Logistic Models; Male; Middle Aged; Prospective Studies; Seizures, Febrile; Statistics, Nonparametric; Vitamin K; Vitamin K Deficiency

We aimed to determine serum 25-hydroxyvitamin D (25(OH)D) and undercarboxylated osteocalcin (ucOC) levels in severe motor and intellectual disabilities (SMID) patients and their association with bone turnover biomarkers.. We assessed vitamin D and K levels as indicators of osteoporosis in institutionalized adults with SMID. From December 2019 to February 2020, 93 institutionalized patients (48 men, 45 women; median age, 49 years) underwent annual routine examinations. Serum ucOC, 25(OH)D, bone-specific alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase A 5b (TRACP-5b) levels as bone formation and resorption markers and calcium and phosphorous levels were measured. Vitamin K deficiency was indirectly assessed based on ucOC levels.. Mean ucOC levels were higher than normal (i.e., vitamin K deficiency). Serum 25(OH)D levels were markedly diminished. Overall, 86% of patients had deficient 25(OH)D levels. These 25(OH)D-deficient patients had higher ucOC levels. Multiple linear regression analysis revealed an inverse correlation between 25(OH)D and ucOC levels. ucOC levels were significantly higher and 25(OH)D levels were significantly lower in tube feeding. TRACP-5b levels were significantly higher in elderly than in young women. BAP and TRACP-5b levels were normal in adults. No relationship existed between vitamin D and antiepileptic drug use.. Vitamin K and D co-deficiency was common in SMID patients. Vitamin K and D deficiencies were worse in tube-fed patients than in oral intake patients. SMID patients should undergo regular monitoring of vitamin D and K levels and supplementation of these vitamins.

Topics: Adult; Aged; Biomarkers; Bone Density; Female; Humans; Institutionalization; Intellectual Disability; Male; Middle Aged; Motor Activity; Motor Skills Disorders; Osteocalcin; Osteoporosis; Persons with Mental Disabilities; Vitamin D; Vitamin D Deficiency; Vitamin K; Vitamin K Deficiency; Vitamins

Patients with chronic kidney disease (CKD) suffer from vitamin K deficiency and are at high risk of vascular calcification (VC) and premature death. We investigated the association of functional vitamin K deficiency with all-cause mortality and whether this association is modified by the presence of VC in CKD stage 5 (CKD G5). Plasma dephosphorylated-uncarboxylated matrix Gla-protein (dp-ucMGP), a circulating marker of functional vitamin K deficiency, and other laboratory and clinical data were determined in 493 CKD G5 patients. VC was assessed in subgroups by Agatston scoring of coronary artery calcium (CAC) and aortic valve calcium (AVC). Backward stepwise regression did not identify dp-ucMGP as an independent determinant of VC. During a median follow-up of 42 months, 93 patients died. Each one standard deviation increment in dp-ucMGP was associated with increased risk of all-cause mortality (sub-hazard ratio (sHR) 1.17; 95% confidence interval, 1.01-1.37) adjusted for age, sex, cardiovascular disease, diabetes, body mass index, inflammation, and dialysis treatment. The association remained significant when further adjusted for CAC and AVC in sub-analyses (sHR 1.22, 1.01-1.48 and 1.27, 1.01-1.60, respectively). In conclusion, functional vitamin K deficiency associates with increased mortality risk that is independent of the presence of VC in patients with CKD G5.

Topics: Adult; Aged; Biomarkers; Calcium-Binding Proteins; Cohort Studies; Extracellular Matrix Proteins; Female; Humans; Male; Matrix Gla Protein; Middle Aged; Renal Insufficiency, Chronic; Survival Rate; Vascular Calcification; Vitamin K; Vitamin K Deficiency

The present cross-sectional clinical study aimed to examine the connection between statin exposure, coronary artery calcification (CAC), and vitamin K-dependent proteins (VKDPs) in patients with cardiovascular (CV) conditions. Two groups of patients were studied: patients with established CV disease (CVD) and healthy patients at moderate risk for CVD (a control group). The groups were also split into statin users and non-users. The following VKDPs were measured in plasma: uncarboxylated Matrix Gla-protein (ucMGP), undercarboxylated (ucOC), and carboxylated osteocalcin (cOC), Gla-rich protein (GRP). CAC score (CACS) was determined by multislice computed tomography. Among all the participants in the study, CACS was more pronounced in statin users compared to non-users; the same was found also among the CVD patients and among the controls. While the levels of ucMGP and GRP did not differ between statin users and non-users, ucOC and ucOC/cOC were significantly elevated in statin users, indicating vitamin K deficiency. There was a positive correlation between the levels of ucOC and CACS in the entire population and in the group of statin users, but not in statin non-users. No association was found between ucMGP or GRP and CACS. Statins had also an impact on the international normalized ratio and interacted with vitamin K antagonists (VKAs). Our results are in agreement with the existing evidence about positive association between statins and vascular calcification. They enlighten to a certain extent the possible mechanisms through which statins may enhance calcium accumulation in arterial wall, namely, by inhibition of vitamin K dependent proteins and functions involved in vascular protection.

Topics: Aged; Biomarkers; Calcium-Binding Proteins; Cardiovascular Diseases; Coronary Artery Disease; Cross-Sectional Studies; Extracellular Matrix Proteins; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inpatients; Male; Matrix Gla Protein; Middle Aged; Osteocalcin; Regression Analysis; Risk; Risk Factors; Tomography, X-Ray Computed; Vascular Calcification; Vitamin K; Vitamin K Deficiency

Vitamin K is a fat-soluble vitamin that plays an important role in blood coagulation and bone formation. Vitamin K has homologues due to differences in the side chain structure, phylloquinone (abbreviated as vitamin K

Topics: Animals; Blood Coagulation; Dimethylallyltranstransferase; Humans; Mice, Knockout; Neurodegenerative Diseases; Osteogenesis; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

It has recently been hypothesized that vitamin K could play a role in COVID-19. We aimed to test the hypotheses that low vitamin K status is a common characteristic of patients hospitalized with COVID-19 compared to population controls and that low vitamin K status predicts mortality in COVID-19 patients. In a cohort of 138 COVID-19 patients and 138 population controls, we measured plasma dephosphorylated-uncarboxylated Matrix Gla Protein (dp-ucMGP), which reflects the functional vitamin K status in peripheral tissue. Forty-three patients died within 90 days from admission. In patients, levels of dp-ucMGP differed significantly between survivors (mean 877; 95% CI: 778; 995) and non-survivors (mean 1445; 95% CI: 1148; 1820). Furthermore, levels of dp-ucMGP (pmol/L) were considerably higher in patients (mean 1022; 95% CI: 912; 1151) compared to controls (mean 509; 95% CI: 485; 540). Cox regression survival analysis showed that increasing levels of dp-ucMGP (reflecting low vitamin K status) were associated with higher mortality risk (sex- and age-adjusted hazard ratio per doubling of dp-ucMGP was 1.49, 95% CI: 1.03; 2.24). The association attenuated and became statistically insignificant after adjustment for co-morbidities (sex, age, CVD, diabetes, BMI, and eGFR adjusted hazard ratio per doubling of dp-ucMGP was 1.22, 95% CI: 0.82; 1.80). In conclusion, we found that low vitamin K status was associated with mortality in patients with COVID-19 in sex- and age-adjusted analyses, but not in analyses additionally adjusted for co-morbidities. Randomized clinical trials would be needed to clarify a potential role, if any, of vitamin K in the course of COVID-19.

Topics: Adult; Aged; Biomarkers; Blood Coagulation; Calcium-Binding Proteins; Cohort Studies; COVID-19; Extracellular Matrix Proteins; Female; Hospital Mortality; Hospitalization; Humans; Male; Matrix Gla Protein; Middle Aged; Proportional Hazards Models; Regression Analysis; SARS-CoV-2; Thrombosis; Vitamin K; Vitamin K Deficiency; Young Adult

Bleeding as an adverse event following immunization (AEFI) that is rarely reported in children, although it can be a parental concern. Bleeding episodes ranging in severity from mild to severe and defined as any external and/or internal bleeding can be caused by acquired or hereditary disorders. This study analyzes whether bleeding episodes in children that were recorded as AEFIs are causally associated with immunization and elaborates their etiology.. A cross-sectional study of 388 AEFI cases in children from West Java Provincial Committee in Indonesia confirmed by case findings from 2000 until 2017.. Of the total number of cases studied, 55 (14%) involved children aged 5 days to 12 years who presented with bleeding and were referred to a provincial hospital. Analysis revealed that 32 cases were most likely caused by acquired prothrombin complex deficiency (APCD) and 30 of these APCD cases were strongly suspected to be manifestations of vitamin K deficiency bleeding (VKDB). All VKDB subjects were aged 5 days to 3 months without a history of administration of prophylactic vitamin K. When a World Health Organization classification was used, most bleeding cases in this study became coincidental events with a temporal association with immunization. A causality assessment suggested that these cases were causally unrelated.. Most cases of bleeding reported as an AEFI were found to be VKDB, which is considered a coincidental event following immunization with a temporal association, and an unrelated category based on the results of a causality assessment. Vitamin K should be administered to all newborns as a prophylactic and AEFI surveillance should be improved based on the low numbers of AEFI reported in Indonesia.

Topics: Child; Cross-Sectional Studies; Female; Hemorrhage; Humans; Immunization; Indonesia; Infant; Infant, Newborn; Male; Vaccination; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

A 70-year-old man underwent a colonoscopy and enhanced CT for scrutiny of his anemia. These examinations revealed rectal cancer(cT4b[rectal mesenteric infiltration], N3M0, cStage Ⅲc). We introduced neoadjuvant chemotherapy(NAC) (cetuximab plus oxaliplatin plus S-1, 4 courses)for this patient and diagnosed ycStage Ⅲc(ycT4bN3M0)after the therapy. We performed laparoscopic total pelvic exenteration with bilateral pelvic lymph node dissection. Cefmetazole was administered as a preventive antibiotic in the perioperative period(intraoperatively to postoperative day 3). On postoperative day 4, intra-abdominal heavy bleeding occurred. Blood examination revealed remarkable coagulation disorder with parameters such as APTT 58.9 sec, PT-INR 3.33, and a remarkably high PIVKA- / Ⅱ score of 11,754 mAU/mL. Based on these findings, the patient was diagnosed with complicated vitamin K(VK)deficiency. The coagulation disorders improved following the administration of VK. VK is a fat-soluble vitamin, and the main absorption pathways are dietary, intestinal bacterial production, and recycling in the VK metabolic cycle. In our case, it was considered that the causes of VK deficiency were a marked decrease in VK intake, impairment of the VK metabolic cycle due to taking antibiotics with a N-methyl-thiotetrazole group, and deficiency of VK accompanying suppression of the intestinal flora by antibiotics. We should also consider VK deficiency when patients are diagnosed with postoperative bleeding.

Topics: Aged; Hemorrhage; Humans; Laparoscopy; Male; Pelvic Exenteration; Rectal Neoplasms; Vitamin K; Vitamin K Deficiency

An 8-month-old child under tuberculosis treatment presented with multiple ecchymotic lesions. A severe coagulopathy was evidenced compatible with vitamin K deficiency [II (3%), VII (2%), IX (3%) and X (1%)]. It was reversed with vitamin K and plasma administration. Rifampicin-induced vitamin K deficiency is very rare, reported only once before, possibly related to an inhibition of vitamin K cycle.

Topics: Antibiotics, Antitubercular; Blood Coagulation Disorders; Child; Humans; Infant; Male; Plasma; Rifampin; Treatment Outcome; Tuberculosis; Vitamin K; Vitamin K Deficiency

Topics: Administration, Oral; History, 20th Century; Humans; Infant, Newborn; Infant, Newborn, Diseases; Injections, Intramuscular; Treatment Refusal; Vitamin K; Vitamin K Deficiency

Topics: Erythrocyte Transfusion; Humans; Infant; Intracranial Thrombosis; Magnetic Resonance Imaging; Male; Plasma; Venous Thrombosis; Vitamin K; Vitamin K Deficiency

Patients with intestinal fat malabsorption and urolithiasis are particularly at risk of acquiring fat-soluble vitamin deficiencies. The aim of the study was to evaluate the vitamin status and metabolic profile before and after the supplementation of fat-soluble vitamins A, D, E and K (ADEK) in 51 patients with fat malabsorption due to different intestinal diseases both with and without urolithiasis. Anthropometric, clinical, blood and 24-h urinary parameters and dietary intake were assessed at baseline and after ADEK supplementation for two weeks. At baseline, serum aspartate aminotransferase (AST) activity was higher in stone formers (SF;

Topics: Adult; Aged; Aspartate Aminotransferases; Cholesterol; Dietary Supplements; Female; Humans; Malabsorption Syndromes; Male; Middle Aged; Prospective Studies; Triglycerides; Urolithiasis; Vitamin A; Vitamin A Deficiency; Vitamin D; Vitamin D Deficiency; Vitamin E; Vitamin E Deficiency; Vitamin K; Vitamin K Deficiency; Vitamins

A low vitamin D and K status has been associated with increased cardiovascular disease (CVD) risk but the evidence of their combined effect on cardiovascular health is limited.. Our study aimed to investigate the prospective association of vitamin D and K status with subclinical measures of cardiovascular health and all-cause mortality among a population of Dutch Caucasians.. We performed an observational prospective study on 601 participants of the Hoorn Study (mean ± SD age: 70 ± 6 y, 50.4% women, BMI: 27.2 ± 4.0 kg/m2), of whom 321 underwent an echocardiogram in 2000-2001 and 2007-2009. Vitamin D and K status was assessed at baseline by serum 25-hydroxyvitamin D [25(OH)D] and plasma desphospho-uncarboxylated matrix-gla protein (dp-ucMGP)-high concentrations indicate low vitamin K status. Vital status was assessed from baseline until 2018. We studied the association of categories of 25(OH)D (stratified by the clinical cutoff of 50 mmol/L) and dp-ucMGP (stratified by the median value of 568 pmol/L) with echocardiographic measures using linear regression and with all-cause mortality using Cox regression, adjusted for confounders.. Compared with markers of normal vitamin D and K status, markers of low vitamin D and K status were prospectively associated with increased left ventricular mass index (5.9 g/m2.7; 95% CI: 1.8, 10.0 g/m2.7). Participants with low vitamin D and K status were also at increased risk of all-cause mortality with an HR of 1.64 (95% CI: 1.12, 2.39) compared with normal vitamin D and K status.. A combination of low vitamin D and K status is associated with adverse cardiac remodeling and increased risk of all-cause mortality in men and women. Future studies should investigate whether vitamin D and K supplementation could help to improve cardiovascular health and to decrease CVD risk.

Topics: Aged; Cardiovascular Diseases; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mortality; Vitamin D; Vitamin D Deficiency; Vitamin K; Vitamin K Deficiency

Covid-19, caused by SARS-CoV-2, has major world-wide health-related and socio-economic consequences. There are large disparities in the burden of Covid-19 with an apparent lower risk of poor outcomes in East Asians compared to populations in the West. A recent study suggested that Covid-19 leads to a severe extrahepatic vitamin K insufficiency, which could lead to impaired activation of extrahepatic proteins like endothelial anticoagulant protein S in the presence of normal hepatic procoagulant activity. This would be compatible with the enhanced thrombogenicity in severe Covid-19. The same study showed that vitamin K antagonists (VKA) that inhibit vitamin K recycling, had a greater impact on procoagulant activity than on the activation of extrahepatic vitamin K-dependent proteins during SARS-CoV-2 infections. A genetic polymorphism in the vitamin K epoxide reductase complex 1, VKORC1 -1639A, is particularly prevalent in East Asia and associates with low vitamin K recycling rates. Carriage of the allele may be regarded as bioequivalent to low-dose VKA use. We speculate that VKORC1 -1639A confers protection against thrombotic complications of Covid-19 and that differences in its allele frequency are partially responsible for the differences in Covid-19 severity between East and West.

Topics: Americas; Asia, Eastern; COVID-19; Europe; Gene Frequency; Humans; Models, Biological; Pandemics; Polymorphism, Single Nucleotide; SARS-CoV-2; Severity of Illness Index; Thrombosis; Vitamin K; Vitamin K Deficiency; Vitamin K Epoxide Reductases

Vitamin K is crucial for many physiological processes such as coagulation, energy metabolism, and arterial calcification prevention due to its involvement in the activation of several vitamin K-dependent proteins. During this activation, vitamin K is converted into vitamin K epoxide, which must be re-reduced by the VKORC1 enzyme. Various

Topics: Animals; Calcium; Diet; Drug Administration Schedule; Gene Expression Regulation, Enzymologic; Genotype; Male; Microsomes, Liver; Point Mutation; Prothrombin Time; Rats; Vitamin K; Vitamin K 3; Vitamin K Deficiency; Vitamin K Epoxide Reductases

Vitamin K is present in the testes though its actual function in male reproduction is poorly understood. This study investigated the harmful effect of extrahepatic vitamin K insufficiency on the testicular structure. Sprague-Dawley rats were fed with a diet containing warfarin for 2, 4 and 8 weeks; control animals received a standard diet without warfarin. It was found that extrahepatic vitamin K deficiency that is induced by warfarin results in histopathological features that range from delayed spermiation, presence of multinucleated giant cells in the seminiferous tubules, germ cells degeneration, asthenozoospermia, oligozoospermia and increase in the percentage of abnormal sperm morphology when compared to the controls. Data obtained from the two groups were analysed using the Student t test. It is concluded that warfarin-induced vitamin K deficiency has a negative impact on spermatogenesis.

Topics: Administration, Oral; Animals; Disease Models, Animal; Humans; Infertility, Male; Male; Rats; Rats, Sprague-Dawley; Seminiferous Tubules; Spermatogenesis; Spermatozoa; Vitamin K; Vitamin K Deficiency; Warfarin

Although there are several reports of intracranial hemorrhage associated with vitamin K deficient bleeding, there are few reported cases of extracranial manifestations, specifically involving the thymus. Here, we discuss the unique case of a 4-week-old infant presenting with scrotal discoloration, respiratory distress, and widened mediastinum, found to have thymic hemorrhage related to confirmed coagulopathy secondary to late-onset vitamin K deficiency bleeding of the newborn.

Topics: Antifibrinolytic Agents; Contusions; Diagnosis, Differential; Genital Diseases, Male; Humans; Infant, Newborn; Male; Mediastinum; Respiratory Distress Syndrome, Newborn; Scrotum; Thymus Gland; Treatment Outcome; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

In the article intended for neonatologists, general practitioners and family doctors, the main causes of hemostatic disorders that lead to the development of hemorrhagic syndrome in newborns and infants are given. The emphasis is on the different forms of neonatal hemorrhagic disease (HD), which is based on the deficiency of vitamin K1, and therefore the bleeding that is observed in children who are breastfed in the first half of life is mostly associated, namely, with vitamin K deficiency. Risk factors of HD depending from the time of the beginning, of the action of one or another factor. The main clinical manifestations of both early and late forms of HD are described, it is shown which of them are mistakenly diagnosed that lead to the appointment of the wrong treatment. The assessment of the need for prevention of late form of bleeding associated with vitamin K deficiency is carried out by determining the concentration in the blood of a functional coagulation marker - PIVKA II. Modern methods of prevention of late bleeding associated with vitamin K1 deficiency, based on nosological units - chronic cholestasis, cystic fibrosis, are presented. The current recommendations on the use of vitamin K1 in newborns and infants of the American Academy of Pediatrics, the scientific community of Canada, Netherlands, Switzerland, Germany, France, the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), the World Health Organization, which are clearly followed by the effects of local peculiarities are described and interpreted. on approaches to the prevention of bleeding associated with vitamin K1 deficiency, which affects the choice of a single dose, the duration of the prophylactic course and the route of administration of vitamin in K1 (phytomenadion). The role of parents in the prevention of vitamin K deficiency is emphasized.

Topics: Breast Feeding; Child; Female; Germany; Humans; Infant; Infant, Newborn; Male; Treatment Outcome; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Few studies assessed the associations between dietary vitamin K and depressive symptoms. We aimed to investigate the association between dietary vitamin K and depressive symptoms in a large cohort of North American People. In this cross-sectional analysis, 4,375 participants that were aged 45⁻79 years from the Osteoarthritis Initiative were included. Dietary vitamin K intake was collected through a semi-quantitative food frequency questionnaire and categorized in quartiles. Depressive symptoms were diagnosed using the 20-item Center for Epidemiologic Studies-Depression (CES-D) ≥ 16. To investigate the associations between vitamin K intake and depressive symptoms, logistic regression analysis were run, which adjusted for potential confounders. Overall, 437 (=10%) subjects had depressive symptoms. After adjusting for 11 confounders, people with the highest dietary vitamin K intake had lower odds of having depressive symptoms (OR = 0.58; 95%CI: 0.43⁻0.80). This effect was only present in people not taking vitamin D supplementation. In conclusion, higher dietary vitamin K intake was significantly associated with a lower presence of depressive symptoms, also after accounting for potential confounders. Future longitudinal research is required to explore the directionality of the association.

Topics: Aged; Cohort Studies; Cross-Sectional Studies; Depression; Diet; Female; Food Analysis; Humans; Male; Middle Aged; Vitamin K; Vitamin K Deficiency

Coagulation disorders due to some antibiotics containing N-methyl-thiotetrazole group and vitamin K (VK) deficiency by microbial substitution in the intestinal flora can occur. We report a case of coagulation disorder under fasting with conventional antibiotics which are not containing N-methyl-thiotetrazole. A 91-year-old man was hospitalized for diagnosis of acute exacerbation of chronic heart failure because of bronchitis. He received treatment of fasting, fluid replacement, antibiotics, and a diuretic. On the 3rd day, left frontal lobe bleeding occurred. We performed conservative treatment with central venous nutrition not containing VK. Administration of antibiotics was completed after 14 days. On the 28th day, catheter-related bloodstream infection developed. Vancomycin and cefazolin were administered. The prothrombin time-international standard ratio (PT-INR) on the 1st day of administration was 1.2; however, it gradually increased to 7.4 on the 7th day of administration. Menatetrenone and fresh frozen plasma were administered as symptomatic treatment. Vancomycin was discontinued because a blood culture was positive for methicillin- susceptible coagulase negative Staphylococcus (CNS). After the 8th day of administration, the PT-INR improved to 1.1, but it increased to 1.9 on the 14th day. VK deficiency due to the antimicrobial drug was predicted. Therefore, VK and fresh frozen plasma were re-administered to improve the PT-INR. The PT-INR returned to normal after administration of cefazolin was terminated. Antimicrobial administration in the long term under the fasting condition can suppress endogenous production of VK by changing intestinal bacteria. And it has been reported that cefazolin which containing Methyl-thiadiazole thiol inhibits VK metabolic cycle and causes coagulation disorder. These reasons seems to a coagulation disorder. Therefore, physicians should monitor the coagulation system in this situation.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Blood Coagulation Disorders; Fasting; Hemorrhage; Humans; Male; Vitamin K; Vitamin K Deficiency

Topics: Humans; Infant, Newborn; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Humans; Infant, Newborn; Vitamin K; Vitamin K Deficiency; Vitamins

Several reports have indicated a possible link between decreasing plasma levels of vitamin K and bone mineral density. It has been suggested that intestinal bacteria contribute to maintenance of vitamin K. Several factors are involved in the reduction of vitamin K in patients with Crohn's disease (CD). We aimed to assess the relationship between gut microbiota and alternative indicators of vitamin K deficiency in patients with CD. We collected the feces of 26 patients with clinically inactive CD. We extracted 16S rRNA from the intestinal bacteria in the feces and amplified it by polymerase chain reaction. The generated polymerase chain reaction product was analyzed using a 16S metagenomic approach by Illumina Miseq platform. Serum undercarboxylated osteocalcin concentration was used as an alternative indicator of vitamin K deficiency. There was a significant negative correlation between serum undercarboxylated osteocalcin and mean Chao1 index in cases of low activity. The diversity of the gut microbiota was significantly lower, and

Topics: Adult; Crohn Disease; Feces; Gastrointestinal Microbiome; Humans; Middle Aged; Osteocalcin; Vitamin K; Vitamin K Deficiency; Young Adult

Zellweger spectrum disorders (ZSDs) are caused by an impairment of peroxisome biogenesis, resulting in multiple metabolic abnormalities. This leads to a range of symptoms, including hepatic dysfunction and coagulopathy. This study evaluated the incidence and severity of coagulopathy and the effect of vitamin K supplementation orally and IV in ZSD.. Data were retrospectively retrieved from the medical records of 30 ZSD patients to study coagulopathy and the effect of vitamin K orally on proteins induced by vitamin K absence (PIVKA-II) levels. Five patients from the cohort with a prolonged prothrombin time, low factor VII, and elevated PIVKA-II levels received 10 mg of vitamin K IV. Laboratory results, including thrombin generation, at baseline and 72 h after vitamin K administration were examined.. In the retrospective cohort, four patients (13.3%) experienced intracranial bleedings and 14 (46.7%) reported minor bleeding. No thrombotic events occurred. PIVKA-II levels decreased 38% after start of vitamin K therapy orally. In the five patients with a coagulopathy, despite treatment with oral administration of vitamin K, vitamin K IV caused an additional decrease (23%) of PIVKA-II levels and increased thrombin generation.. Bleeding complications frequently occur in ZSD patients due to liver disease and vitamin K deficiency. Vitamin K deficiency is partly corrected by vitamin K supplementation orally, and vitamin K administered IV additionally improves vitamin K status, as shown by further decrease of PIVKA-II and improved thrombin generation.

Topics: Administration, Intravenous; Administration, Oral; Adolescent; Biomarkers; Blood Coagulation; Blood Coagulation Disorders; Child; Dietary Supplements; Female; Hemorrhage; Humans; Incidence; Male; Netherlands; Pilot Projects; Proof of Concept Study; Prospective Studies; Protein Precursors; Prothrombin; Retrospective Studies; Severity of Illness Index; Treatment Outcome; Vitamin K; Vitamin K Deficiency; Young Adult; Zellweger Syndrome

Topics: Adolescent; Apolipoproteins E; Cystic Fibrosis; Dietary Supplements; Female; Humans; Male; Pharmacogenomic Testing; Polymorphism, Genetic; Treatment Outcome; Vitamin K; Vitamin K Deficiency; Vitamins; Young Adult

We present here a late preterm infant with extensive brain lesions resulting from vitamin K deficiency. A female infant was born after 35 weeks of gestation by emergent cesarean section because of non-reassuring fetal status. Her mother had severe eating disorder and recurrent vomiting since early pregnancy. She was immediately intubated and ventilated because she was extremely pale, hypotonic, and non-reactive. Cerebral magnetic resonance imaging immediately after birth showed intraparenchymal hemorrhage in the left frontal lobe and cerebellum, marked cerebral edema, and cerebellar hypoplasia. Coagulation studies of the infant showed hepaplastin test <5%, prolonged PT and APTT, and a marked elevation of protein induced by vitamin K absence or antagonist-II. This case highlighted a potential risk of intracranial bleeding due to maternal vitamin K deficiency and difficulty in its prediction before delivery. Vitamin K supplementation to high risk mothers might be indispensable for preventing severe fetal vitamin K deficiency. Even when coagulation studies in mothers is normal, it is imperative to provide vitamin K supplementation for total protection.

Topics: Adult; Feeding and Eating Disorders; Female; Humans; Infant, Newborn; Intracranial Hemorrhages; Maternal Nutritional Physiological Phenomena; Mothers; Pregnancy; Pregnancy Complications, Hematologic; Prenatal Exposure Delayed Effects; Treatment Outcome; Vitamin K; Vitamin K Deficiency; Vomiting

We examined the association between vitamin K status and physical functioning over 13 years in the Longitudinal Aging Study Amsterdam.. Longitudinal cohort study of 633 community-dwelling adults from the Longitudinal Aging Study Amsterdam (LASA) aged 55-65 years (54% women).. At baseline (2002-2003), plasma desphospho-uncarboxylated matrix Gla protein (dp-ucMGP) was measured with a sandwich ELISA as a marker of vitamin K status. The outcome measures handgrip strength, calf circumference, self-reported functional limitations and functional performance were obtained at baseline and four follow-up examinations. We used generalized estimating equations to determine the relationship between dp-ucMGP tertiles and the various outcome measurements after adjusting for potential confounders. The lowest dp-ucMGP tertile reflects a high vitamin K status and was the reference.. Mean dp-ucMGP was 376 ± 233 pmol/L and mean follow-up was 11.1 years. Participants showed a decline in the outcome measures over time. Compared with the lowest tertile, the highest dp-ucMGP tertile had: lower handgrip strength, 1.1 kg (95% confidence interval (-2.1, -0.1; P-trend <0.001); smaller calf circumference, -0.5 cm (-0.9 -0.1; P-trend = 0.018); and, only among women, a 0.7-point poorer functional performance score (-1.1, -0.3; P-interaction = 0.002). Dp-ucMGP was not related to self-reported functional limitations. No interaction effects between time and dp-ucMGP were observed.. Low vitamin K status was associated with lower handgrip strength, smaller calf circumference, and, in women only, with poorer functional performance score. A low vitamin K status was however not related to the 13-year decline in these measures.

Topics: Aged; Aging; Biomarkers; Calcium-Binding Proteins; Extracellular Matrix Proteins; Female; Hand Strength; Humans; Longitudinal Studies; Male; Matrix Gla Protein; Middle Aged; Muscle Strength; Vitamin K; Vitamin K Deficiency

Topics: Cerebral Hemorrhage; Emigrants and Immigrants; Germany; Humans; Infant Welfare; Infant, Newborn; Male; Psychomotor Agitation; Vitamin K; Vitamin K Deficiency; Vomiting

Topics: Humans; Infant, Newborn; Parents; Treatment Refusal; Vitamin K; Vitamin K Deficiency

Topics: Calciphylaxis; Calcium-Binding Proteins; Extracellular Matrix Proteins; Humans; Matrix Gla Protein; Renal Dialysis; Vitamin K; Vitamin K Deficiency

Topics: Adult; Female; Hematoma, Subdural; Humans; Infant, Newborn; Mothers; Pregnancy; Pregnancy Complications; Prognosis; Ultrasonography, Prenatal; Vitamin K; Vitamin K Deficiency; Vitamins

Topics: Adult; Aged; Calcifediol; Calcium-Binding Proteins; Cross-Sectional Studies; Extracellular Matrix Proteins; Female; Humans; Male; Matrix Gla Protein; Middle Aged; Polymorphism, Single Nucleotide; Pulse Wave Analysis; Receptors, Calcitriol; Regression Analysis; Vascular Stiffness; Vitamin D; Vitamin K; Vitamin K Deficiency

This article presents the case of a 6-week-old infant who, despite oral vitamin K prophylaxis and otherwise normal developmental progress, suffered a severe intracerebral and subdural hemorrhage, which required surgical evacuation. The interdisciplinary approach is described with emphasis on the management of hemostasis. Furthermore, the clinical picture of intracranial bleeding due to vitamin K deficiency, which is nowadays rare in the Western World, is described in the anesthesiology literature for the first time. The usual recommendations regarding prophylaxis as well as certain risk factors are presented.

Topics: Anesthesiologists; Blood Coagulation Disorders; Hemostasis; Hemostatics; Humans; Infant; Infant, Newborn; Intracranial Hemorrhages; Male; Risk Factors; Thrombelastography; Vitamin K; Vitamin K Deficiency

Elastin is a unique protein providing deformability and resilience to dynamic tissues, such as arteries and lungs. It is an absolute basic requirement for circulation and respiration. Elastin can be degraded by elastases and has a high calcium affinity. Elastin calcification and elastin degradation are two pathological processes that impair elastin's functioning. Furthermore, elastin degradation can be associated to elastin calcification. Matrix Gla Protein (MGP) is probably the most potent natural inhibitor of elastin calcification and requires vitamin K for its activation. Measuring circulating levels of inactive MGP (dp-ucMGP) is a frequently used method to assess vitamin K status. Dp-ucMGP reflects the burden of vitamin K-dependent proteins that have not been activated by vitamin K and could therefore best be regarded as a biomarker of a vitamin K deficit. Dp-ucMGP levels decrease after vitamin K supplementation. Since the amino acids desmosine and isodesmosine (DES) are unique to crosslinked elastin fibers, systemic elastin degradation can be assessed with the plasma DES assay. Recently, we discovered a strong correlation between plasma dp-ucMGP and plasma DES levels in both patients with chronic obstructive pulmonary disease (COPD) and controls. The 'Vitamin K deficit and elastolysis theory' posits that elastin degradation causes a rise in the vitamin K deficit and implies that vitamin K supplementation could be preventing elastin degradation. If this hypothesis holds true and is universally found in every state and condition, it will have an unprecedented impact on the management of every single pulmonary disease characterized by accelerated elastin degradation, such as alpha-1 antitrypsin deficiency, bronchiectasis, COPD and cystic fibrosis. Theoretically, a plasma dp-ucMGP concentration of zero would be associated with a near-complete standstill of elastin degradation and disease progression in patients with any of these debilitating conditions.

Topics: alpha 1-Antitrypsin; Biomarkers; Calcium; Calcium-Binding Proteins; Desmosine; Elasticity; Elastin; Extracellular Matrix Proteins; Humans; Isodesmosine; Lung Diseases; Matrix Gla Protein; Models, Biological; Vitamin K; Vitamin K Deficiency

Topics: Dietary Supplements; Humans; Renal Insufficiency, Chronic; Vitamin K; Vitamin K Deficiency

Vitamin K is the collective term for compounds that share a 2-methyl-1,4-naphthoquinone ring, but differ in the side-chain at the 3-position. We synthesized novel 2-methyl-1,4-naphthoquinone derivatives with different side chain length at the 3-position. Derivatives with C-14 and C-16 tails showed the highest in vitro bioactivity resulting in 2.5 and 2-fold higher carboxylated osteocalcin synthesis in MG63 cells than menaquinone-4 (MK-4, form of vitamin K2). Longer side chain lengths resulted in lower bioactivity. The in vivo vitamin K activity of the C-14 tail derivative was further tested in WKY rats receiving a vitamin K-deficient diet that resulted in a 40% decrease of prothrombin activity. The C-14 tail derivative was able to counteract the effects on vitamin K deficiency induced by the diet and resulted in the complete restoration of prothrombin activity. Compared to naturally occurring forms of vitamin K, synthetic vitamin K derivatives may have higher bioactivity and different pharmacological characteristics that are more favorable for use as supplements or in clinical settings.

Topics: Animals; Carbon-Carbon Ligases; Cell Line, Tumor; Enzyme Activators; Humans; Molecular Structure; Osteocalcin; Prothrombin; Rats, Inbred WKY; Vitamin K; Vitamin K 2; Vitamin K Deficiency

Topics: Humans; Infant, Newborn; Parents; Treatment Refusal; Vitamin K; Vitamin K Deficiency

The available data on the influence of liver cirrhosis on vitamin K status in CF patients is scarce. Therefore, the aims of the present study were to assess the prevalence of vitamin K deficiency in cirrhotic CF subjects and to determine whether it correlates with liver cirrhosis. The study group comprised of 27 CF patients with and 63 without liver cirrhosis. Vitamin K status was assessed using prothrombin induced by vitamin K absence (PIVKA-II) and the percentage of undercarboxylated osteocalcin (u-OC). PIVKA-II concentrations were higher in cirrhotic than in non-cirrhotic CF patients (median [1st-3rd quartile]: 3.2ng/ml [1.0-10.0] vs. 1.3ng/ml [0.2-2.6], p=0.0029). However, the differences in u-OC percentages between the studied groups did not reach the level of significance (49.4% [7.0-73.8] vs. 8.0% [2.6-59.1], p=0.0501). Based on multiple linear regression analysis the dose of vitamin K and F508del mutation were potentially defined as determinants of vitamin K deficiency. Liver cirrhosis was not documented to be an independent risk factor. In CF patients with liver cirrhosis vitamin K deficiency is not only more frequent, but also more severe. However, not liver cirrhosis, but the presence of a F508del CFTR mutation constitutes an independent risk factor for vitamin K deficiency.

Topics: Adolescent; Biomarkers; Child; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Female; Humans; Linear Models; Liver Cirrhosis; Male; Osteocalcin; Poland; Prospective Studies; Protein Precursors; Prothrombin; Risk Factors; Vitamin K; Vitamin K Deficiency; Young Adult

Vitamin K-dependent proteins (VKDPs), which require post-translational modification to achieve biological activity, seem to contribute to thrombus formation, vascular calcification, and vessel stiffness. Whether VKDP activity is prospectively associated with incident cardiovascular disease has not been studied.. VKDP activity was determined by measuring circulating des-γ-carboxy prothrombin concentrations in a random sample of 709 multiethnic adults free of cardiovascular disease drawn from the Multi-Ethnic Study of Atherosclerosis (MESA). Lower des-γ-carboxy prothrombin concentrations reflect greater VKDP activity. Subjects were followed up for the risk of ischemic cardiovascular disease (coronary heart disease, stroke, and fatal cardiovascular disease) for 11.0 years of follow-up. A total of 75 first ischemic CVD events occurred during follow-up. The incidence of ischemic cardiovascular disease increased progressively across des-γ-carboxy prothrombin quartiles, with event rates of 5.9 and 11.7 per 1000 person-years in the lowest and highest quartiles. In analyses adjusted for traditional cardiovascular risk factors and measures of vitamin K intake, a doubling of des-γ-carboxy prothrombin concentration was associated with a 1.53 (95% confidence interval, 1.09-2.13; P=0.008) higher risk of incident ischemic cardiovascular disease. The association was consistent across strata of participants with diabetes mellitus, hypertension, renal impairment, and low vitamin K nutritional intake.. In this sample of middle-aged and older adults, VKDP activity was associated with incident ischemic cardiovascular events. Further studies to understand the role of this large class of proteins in cardiovascular disease are warranted.

Topics: Aged; Aged, 80 and over; Atherosclerosis; Biomarkers; Female; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Ischemia; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Protein Precursors; Prothrombin; Risk Assessment; Risk Factors; Stroke; Time Factors; United States; Vitamin K; Vitamin K Deficiency

Protein induced by vitamin K absence (PIVKA)-II, inactive precursor of prothrombin, is elevated in vitamin K (VK) deficiency. Our aims were to find the prevalence of VK deficiency in neonates, assess the utility of international normalized ratio (INR) as a screening tool, and explore the relationship between PIVKA-II, activated partial thromboplastin time (aPTT) and VK dependent anticoagulants.. INR, aPTT, PIVKA-II, and proteins C and S activities were measured in neonatal cord blood prior to VK administration.. We found 45% of neonates had subclinical VK deficiency based on PIVKA-II levels and 7% based on INR. Receiver operating characteristic (ROC) analysis assessed the utility of INR in detecting >4 ng/mL of PIVKA-II and ROC of the area under the curve was 0.70 (95% CI 0.46-0.92, p = 0.07). Proteins C and S activities were normal for age and did not correlate with PIVKA-II [(r = 0.40, p = 0.14) and (r = 0.29, p = 0.29), respectively]. There was no association between aPTT and PIVKA-II (p = 0.83).. PIVKA-II seems to be a sensitive indicator of mild VK deficiency. Further studies are needed to investigate the lack of relationship between PIVKA-II and functional protein C or S levels.

Topics: Biomarkers; Female; Fetal Blood; Humans; Infant, Newborn; International Normalized Ratio; Nutritional Status; Predictive Value of Tests; Pregnancy; Prenatal Nutritional Physiological Phenomena; Protein C; Protein Precursors; Protein S; Prothrombin; Prothrombin Time; Vitamin K; Vitamin K Deficiency

There has been limited characterization of biological variables that impact vitamin K metabolism. This gap in knowledge can limit the translation of data obtained from preclinical animal studies to future human studies.. The purpose of this study was to determine the effects of diet, sex, and housing on serum, tissue, and fecal vitamin K concentrations and gene expression in C57BL6 mice during dietary vitamin K manipulation.. C57BL6 4-mo-old male and female mice were randomly assigned to conventional or suspended-wire cages and fed control [1400 ± 80 μg phylloquinone (PK)/kg] or deficient (31 ± 0.45 μg PK/kg) diets for 28 d in a factorial design. PK and menaquinone (MK) 4 plasma and tissue concentrations were measured by HPLC. Long-chain MKs were measured in all matrices by LC-atmospheric pressure chemical ionization-mass spectrometry. Gene expression was quantified by reverse transcriptase-polymerase chain reaction in the liver, brain, kidney, pancreas, and adipose tissue.. Male and female mice responded differently to dietary manipulation in a tissue-dependent manner. In mice fed the control diet, females had ∼3-fold more MK4 in the brain and mesenteric adipose tissue than did males and 100% greater PK concentrations in the liver, kidney, and mesenteric adipose tissue than did males. In mice fed the deficient diet, kidney MK4 concentrations were ∼4-fold greater in females than in males, and there were no differences in other tissues. Males and females differed in the expression of vitamin K expoxide reductase complex 1 (Vkorc1) in mesenteric adipose tissue and the pancreas and ubiA domain-containing protein 1 (Ubiad1) in the kidney and brain. There was no effect of housing on serum, tissue, or fecal concentrations of any vitamin K form.. Vitamin K concentrations and expression of key metabolic enzymes differ between male and female mice and in response to the dietary PK concentration. Identifying factors that may impact study design and outcomes of interest is critical to optimize study parameters examining vitamin K metabolism in animal models.

Topics: Adipose Tissue; Animals; Brain; Diet; Dimethylallyltranstransferase; Female; Housing; Housing, Animal; Kidney; Liver; Male; Membrane Proteins; Mesentery; Mice, Inbred C57BL; Pancreas; Sex Factors; Tissue Distribution; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency; Vitamin K Epoxide Reductases

Osteoporosis is a chief complication in patients with anorexia nervosa. Serum levels of undercarboxylated osteocalcin reflect serum and bone vitamin K deficiency. We investigated vitamin K status in patients with anorexia nervosa to help establish prevention and treatment recommendations for osteoporosis.. Fifty-four female amenorrheic patients with anorexia nervosa (29 restricting-type and 25 binge eating/purging type) (age, 28.0 (26.7-31.1) (mean (95% CI)) years; body mass index, 14.8 (14.1-15.5) kg/m(2), duration of illness; 107.3 (88.5-126.0) months) and 15 age-matched healthy females were included in this study. We measured serum levels of undercarboxylated osteocalcin, biochemical and nutritional markers, and bone metabolic markers. Dietary vitamin K intake was evaluated by a questionnaire.. Lumbar bone mineral density and T-scores in patients with anorexia nervosa were 0.756 (0.721-0.790) g/cm(2) and -2.4 (-2.1 to -2.7), respectively, indicating bone loss. Serum levels of undercarboxylated osteocalcin in patients with anorexia nervosa were significantly higher than those of controls. The 17% of restricting type and 40% of binge eating/purging type anorexia nervosa patients, serum levels of undercarboxylated osteocalcin were higher than 4.5 ng/ml and were diagnosed with vitamin K deficiency. Serum levels of undercarboxylated osteocalcin correlated significantly and negatively with vitamin K intake in patients with anorexia nervosa.. Patients with anorexia nervosa had vitamin K deficiency. Since a supplement of vitamin K might be effective for maintaining bone quality, we provide recommendations regarding vitamin K intake for prevention and treatment of osteoporosis in patients with AN.

Topics: Adult; Anorexia Nervosa; Biomarkers; Body Mass Index; Bone and Bones; Bone Density; Bone Diseases, Metabolic; Bulimia Nervosa; Case-Control Studies; Female; Humans; Nutritional Status; Osteocalcin; Osteoporosis; Surveys and Questionnaires; Vitamin K; Vitamin K Deficiency

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Recommended Dietary Allowances; Vitamin A; Vitamin A Deficiency; Vitamin D; Vitamin D Deficiency; Vitamin E; Vitamin E Deficiency; Vitamin K; Vitamin K Deficiency; Vitamins; Young Adult

Vitamin K modulates calcification by activating calcification inhibitors such as matrix Gla protein (MGP). In kidney transplant recipients, vitamin K insufficiency is common, but implications for long-term outcomes are unclear.. Single-center observational study with a longitudinal design.. 518 stable kidney transplant recipients; 56% men; mean age, 51±12 (SD) years; and a median of 6 (IQR, 3-12) years after kidney transplantation.. Plasma desphosphorylated-uncarboxylated MGP (dp-ucMGP) levels, reflecting vitamin K status.. All-cause mortality and transplant failure.. At inclusion, median dp-ucMGP level was 1,038 (IQR, 733-1,536) pmol/L, with 473 (91%) patients having vitamin K insufficiency (defined as dp-ucMGP>500pmol/L). During a median follow-up of 9.8 (IQR, 8.5-10.2) years, 152 (29%) patients died and 54 (10%) developed transplant failure. Patients in the highest quartile of dp-ucMGP were at considerably higher mortality risk compared with patients in the lowest quartile (HR, 3.10; 95% CI, 1.87-5.12; P for trend<0.001; P for quartile 1 [Q1] vs Q4<0.001). After adjustment for potential confounders, including kidney function and exclusion of patients treated with a vitamin K antagonist, this association remained significant. Patients in the highest quartile also were at higher risk of developing transplant failure (HR, 2.61; 95% CI, 1.22-5.57; P for trend=0.004; P for Q1 vs Q4=0.01), but this association was lost after adjustment for baseline kidney function (HR, 1.20; 95% CI, 0.52-2.75; P for trend=0.6; P for Q1 vs Q4=0.7).. Although MGP exists as various species, only dp-ucMGP was measured. No data were available for vascular calcification as an intermediate end point.. Vitamin K insufficiency, that is, a high circulating level of dp-ucMGP, is highly prevalent in stable kidney transplant recipients and is associated independently with increased risk of mortality. Future studies should address whether vitamin K supplementation may lead to improved outcomes after kidney transplantation.

Topics: Adult; Aged; Biomarkers; Calcium-Binding Proteins; Cohort Studies; Extracellular Matrix Proteins; Female; Follow-Up Studies; Humans; Kidney Transplantation; Longitudinal Studies; Male; Matrix Gla Protein; Middle Aged; Mortality; Vitamin K; Vitamin K Deficiency

Micronutrient deficiencies occur in morbidly obese patients. The aim of this study was to assess vitamin deficiencies prior to bariatric surgery including vitamin K about which there is little data in this population.. A prospective assessment of 118 consecutive patients was performed. Clinical allied with haematological and biochemical variables were measured. Micronutrients measured included vitamins K1 , PIVKA-II (protein-induced in vitamin K absence factor II), vitamin D, vitamin B12 (holotranscobalamin), iron, transferrin and folate.. Patients were aged 49 ± 11 [mean (SD, standard deviation)] years, body mass index (BMI) 50 ± 8 kg/m(2), 66% female and 78% Caucasian. Hypertension was present in 47% and type 2 diabetes in 32%. Vitamin D supplements had been prescribed in 8%. Micronutrient insufficiencies were found for vitamin K (40%), vitamin D (92%) and vitamin B12 (25%), and also iron (44%) and folate (18%). Normocalcaemic vitamin D insufficiency with secondary hyperparathyroidism was present in 18%. Iron and transferrin levels were associated with age, sex and estimated glomerular filtration rate. Vitamin K levels were associated with age, and inversely with BMI and diabetes mellitus; and PIVKA-II with smoking, triglycerides and liver function markers. Vitamin D levels were associated with statin use and prescription of supplements and inversely with BMI. Vitamin B12 levels were associated with ethnicity and HbA1c.. Micronutrient status shows differing relationships with age, gender and BMI. Vitamin K insufficiency was present in 40% and not related to deficiencies in other vitamins or micronutrients. Vitamin D and vitamin K supplementation should be considered prebariatric surgery in patients with diabetes or severe insulin resistance.

Topics: Adolescent; Adult; Aged; Bariatric Surgery; Female; Humans; Male; Micronutrients; Middle Aged; Obesity, Morbid; Preoperative Period; Prevalence; Prospective Studies; Vitamin D Deficiency; Vitamin K; Vitamin K Deficiency; Vitamins; Young Adult

Vitamin K deficiency is associated with malnutrition in some complications, such as hyperemesis gravidarum, active gastrointestinal diseases, and psychological disorders. Maternal vitamin K deficiency can cause fetal bleeding, in particular, fetal intracranial hemorrhage. Although fetal hemorrhage is uncommon, severe damage to the fetus may be inevitable. We describe a pregnant woman with vitamin K deficiency possibly due to hyperemesis gravidarum. The patient was treated for the deficiency, and no fetal or neonatal hemorrhagic diseases were manifested.

Topics: Administration, Oral; Adult; Blood Coagulation; Blood Coagulation Tests; Dietary Supplements; Female; Fetal Blood; Humans; Hyperemesis Gravidarum; Live Birth; Maternal Nutritional Physiological Phenomena; Nutritional Status; Nutritional Support; Pregnancy; Pregnancy Complications, Hematologic; Treatment Outcome; Vitamin K; Vitamin K Deficiency

Vitamin K intake is considered as a controllable contributor to warfarin sensitivity. It is restricted in warfarin-treated patients. However, little study has assessed the vitamin K status in warfarin-treated patients. We directly measured plasma vitamin K in warfarin-treated patients and evaluated its effect on anticoagulation.. A total of 302 plasma vitamin K concentrations were assessed using high-performance liquid chromatography for 203 outpatients with atrial fibrillation under warfarin treatment. Clinical and laboratory information including warfarin dosage, plasma warfarin concentrations, prothrombin time international normalized ratio (PT INR) and CYP2C9/VKORC1 genotypes was reviewed retrospectively. The anticoagulation stability (intra-individual variability, frequency of PT INR tests and complications) was investigated in 163 patients with long-term warfarin therapy. Plasma vitamin K was measured in 40 healthy subjects and in 40 patients before and after initial warfarin treatment.. Vitamin K concentrations were significantly decreased after the initiation of warfarin treatment (before treatment: 1.72 ng/ml; after treatment: 0.59 ng/ml, P<0.05). There was a large inter-individual variability in vitamin K levels (0.2-4.2 ng/ml) in warfarin-treated patients. PT INR was more frequently checked in patients with low plasma vitamin K levels than in those with high vitamin K levels (9.5 times/year vs 7.5 times/year, P=0.029). Two patients with gross hematuria showed very low vitamin K levels (<0.4 ng/ml).. We found high inter- and intra-individual variability in vitamin K concentration in warfarin-treated patients. Low vitamin K concentration in warfarin-treated patients suggested excessive dietary restriction. Plasma vitamin K measurement would be helpful for dietary control and anticoagulation stability.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Diet; Drug Monitoring; Enzyme Inhibitors; Female; Food-Drug Interactions; Hematuria; Humans; International Normalized Ratio; Male; Middle Aged; Nutritional Status; Republic of Korea; Retrospective Studies; Vitamin K; Vitamin K Deficiency; Vitamin K Epoxide Reductases; Warfarin

Cystic fibrosis (CF) patients are at high risk for vitamin K deficiency. The effects of vitamin K supplementation are very ambiguous. Therefore, we aimed to define the determinants of vitamin K deficiency in a large cohort of supplemented - 146 (86.9%) and non-supplemented - 22 (13.1%) CF patients. Vitamin K status was assessed using prothrombin inducted by vitamin K absence (PIVKA-II) and undercarboxylated osteocalcin (u-OC). The pathological PIVKA-II concentration (≥ 2 ng/ml) and abnormal percentage of osteocalcin (≥ 20%) were found in 72 (42.8%) and 60 (35.7%) subjects, respectively. We found that liver involvement, diabetes, and glucocorticoid therapy were potential risk factors for vitamin K deficiency. Pathological concentrations of PIVKA-II occurred more frequently in patients with pancreatic insufficiency and those who have two severe mutations in both alleles of the CFTR gene. Pathological percentage of u-OC was found more frequently in adult CF patients and those not receiving vitamin K. However, it seems that there are no good predictive factors of vitamin K deficiency in CF patients in everyday clinical care. Early vitamin K supplementation in CF patients seems to be warranted. It is impossible to clearly determine the supplementation dose. Therefore, constant monitoring of vitamin K status seems to be justified.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Biomarkers; Child; Child, Preschool; Cohort Studies; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Dietary Supplements; Female; Genotype; Glucocorticoids; Humans; Immunoassay; Infant; International Normalized Ratio; Male; Nutritional Status; Osteocalcin; Polymorphism, Single Nucleotide; Protein Precursors; Prothrombin; Pseudomonas Infections; Regression Analysis; Risk Factors; Vitamin K; Vitamin K Deficiency; Young Adult

Topics: Aged; Antifibrinolytic Agents; Atrophy; Biological Availability; Cognition Disorders; Female; Hippocampus; Humans; Intelligence Tests; Magnetic Resonance Imaging; Male; Neuroimaging; Sphingolipids; Statistics as Topic; Vitamin K; Vitamin K Deficiency

The aim of this study was to examine the association between dephospho-uncarboxylated matrix Gla protein (dp-ucMGP), an indicator of vitamin K status, and cognitive decline, and the modifying role of 25(OH)D.. Longitudinal study with six years follow-up.. Community based.. 599 participants of the Longitudinal Aging Study Amsterdam (aged 55-65 years).. Information processing speed and a composite Z-score by combining three domains of cognition reflecting general cognitive functioning.. Generalized estimating equations (GEE) showed no significant associations between dp-ucMGP and decline in general cognitive functioning. Vitamin D modified the association between dp-ucMGP and speed of information processing (p<0.05). In the group with a 25(OH)D concentration > 50 nmol/l, the highest tertile of dp-ucMGP (>406 pmol/l), which corresponds to lower vitamin K levels, was associated with 1.5 higher score on information processing speed (p=0.023) as compared to the lowest tertile of dp-ucMGP.. In contrast to our hypothesis, a suboptimal vitamin K was not associated with cognitive decline in middle-aged adults.

Topics: Calcium-Binding Proteins; Cognition; Cognition Disorders; Extracellular Matrix Proteins; Female; Humans; Longitudinal Studies; Male; Matrix Gla Protein; Middle Aged; Nutritional Status; Vitamin D; Vitamin K; Vitamin K Deficiency; Vitamins

Vitamin K deficiency bleeding (VKDB) in infancy is a serious but preventable cause of mortality or permanent disability. Lack of epidemiologic data for VKDB in sub-Saharan Africa hinders development and implementation of effective prevention strategies. We used convenience sampling to consecutively enroll mothers delivering in a southwestern Uganda Hospital. We collected socio-demographic and dietary information, and paired samples of maternal venous and neonatal cord blood for the immunoassay of undercarboxylated prothrombin (PIVKA-II), a sensitive marker of functional vitamin K (VK) insufficiency. We used univariable and multivariable logistic regression models to identify predictors of VK insufficiency. We detected PIVKA-II of ≥0.2 AU (Arbitrary Units per mL)/mL (indicative of VK insufficiency) in 33.3% (47/141) of mothers and 66% (93/141) of newborns. Importantly, 22% of babies had PIVKA-II concentrations ≥5.0 AU/mL, likely to be associated with abnormal coagulation indices. We found no significant predictors of newborn VK insufficiency, including infant weight (AOR (adjusted odds ratio) 1.85, 95% CI (confidence interval) 0.15-22.49), gender (AOR 0.54, 95% CI 0.26-1.11), term birth (AOR 0.72, 95% CI 0.20-2.62), maternal VK-rich diet (AOR 1.13, 95% CI 0.55-2.35) or maternal VK insufficiency (AOR 0.99, 95% CI 0.47-2.10). VK insufficiency is common among mothers and newborn babies in southwestern Uganda, which in one fifth of babies nears overt deficiency. Lack of identifiable predictors of newborn VK insufficiency support strategies for universal VK prophylaxis to newborns to prevent VKDB.

Topics: Adult; Biomarkers; Female; Humans; Infant, Newborn; Logistic Models; Male; Nutritional Status; Pregnancy; Pregnancy Complications; Prenatal Nutritional Physiological Phenomena; Protein Precursors; Prothrombin; Uganda; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding; Young Adult

In chronic kidney disease, vitamin K-dependent proteins, including the calcification inhibitor matrix Gla protein, are largely uncarboxylated indicating that functional vitamin K deficiency may contribute to uremic vascular calcification. Since the effects of uremia on the vitamin K cycle are unknown, we investigated the influence of uremia and vitamin K supplementation on the activity of the vitamin K cycle and extraosseous calcification. Uremia was induced in rats by an adenine-supplemented diet and vitamin K1 or K2 was administered over 4 and 7 weeks. After 4 weeks of adenine diet, the activity of the vitamin K cycle enzyme γ-carboxylase but not the activities of DT-diaphorase or vitamin K epoxide reductase were reduced. Serum levels of undercarboxylated matrix Gla protein increased, indicating functional vitamin K deficiency. There was no light microscopy-detectable calcification at this stage but chemically determined aortic and renal calcium content was increased. Vitamin K treatment reduced aortic and renal calcium content after 4 weeks. Seven weeks of uremia induced overt calcification in the aorta, heart, and kidneys; however, addition of vitamin K restored intrarenal γ-carboxylase activity and overstimulated it in the liver along with reducing heart and kidney calcification. Thus, uremic vitamin K deficiency may partially result from a reduction of the γ-carboxylase activity which possibly contributes to calcification. Pharmacological vitamin K supplementation restored the vitamin K cycle and slowed development of soft tissue calcification in experimental uremia.

Topics: Animals; Aorta; Calcinosis; Calcium-Binding Proteins; Carbon-Carbon Ligases; Extracellular Matrix Proteins; Kidney; Liver; Male; Matrix Gla Protein; NAD(P)H Dehydrogenase (Quinone); Rats; Rats, Wistar; Uremia; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

We report a case of absolute vitamin K deficiency (VKD) diagnosed by measuring serum VK levels in an elderly woman undergoing warfarin therapy. A 78-year-old woman was admitted to our hospital because of dyspnea and sore throat diagnosed as pharyngitis 1 week before admission. On admission, the sore throat had exacerbated and dyspnea developed. She had history of atrial fibrillation, for which warfarin 1.5 mg/d was started approximately 10 years prior and her international normalized ratio (INR) had been maintained at an acceptable therapeutic level. Blood results revealed unmeasurable INR and abnormally prolonged activated partial thromboplastin time (APTT). She was diagnosed with adenoiditis and warfarin-related coagulopathy and administered intravenous VK (20 mg) and fresh frozen plasma (FFP; 4 U), which improved INR and APTT. Since the coagulopathy responded to intravenous VK administration, the patient was clinically diagnosed with warfarin-related relative VKD. Approximately 1 month later, she returned with complaints of sore throat. Blood results indicated abnormal INR (7.22) and APTT (N80.0 s). She was diagnosed with recurrent adenoiditis and VK deficient coagulopathy. The patient’s serum VK levels were low (VK1 level, 0.13 ng/mL; VK2 levels, 0.85 ng/mL). Initial treatment of VK (20 mg) and FFP followed by intravenous VK (20 mg/d) for 6 days, her symptoms dissipated. Warfarin was suspected to have caused absolute VKD. Severe coagulopathy in patients undergoing warfarin therapy is primarily caused by, relative VKD. However, the possibility of warfarin-related absolute VKD should be suspected when INRis not sufficiently improved by intravenous VK administration.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Emergency Service, Hospital; Female; Humans; Vitamin K; Vitamin K Deficiency; Vitamins; Warfarin

Vitamin K is an essential element in the coagulation, which is also involved in gamma-carboxylation reactions of proteins as osteocalcin, which may exert a protective effect against age-dependent bone loss. But there is also evidence that both osteocalcin as vitamin K can have a benefit on the metabolism of glucose, insulin sensitivity and type 2 diabetes mellitus. Therefore, the aim of the present study is to analyse the adequacy of vitamin K intake and food sources in a representative sample of Spanish adults.. A sample of 1068 adults (521 men and 547 women) with ages ranging from 17 to 60 years, was selected in ten Spanish provinces to constitute a representative sample of the population nationwide. The dietary study was carried out by using a "Food record questionnaire" for 3 consecutive days, including a Sunday. Personal, anthropometric and health data were also collected.. The intake of vitamin K (170.2 ± 14.5 μg/day) was lower than the established adequate intake for vitamin in the 30.2% of the studied participants. Vitamin intake increases with age (r = 0.201, p < 0.05), in fact, those participants who meet the adequate intake are older (34.5 ± 12.8 years) than those who do not meet the adequate intake (with a mean age 29.1 ± 11.9 years) (p < 0.001). Vitamin K intake also increases with weight (r = 0.106, p < 0.05) and height (r = 0.282, p < 0.05), however the participants with overweight/obesity have a significantly lower intake (168.2 ± 13.5 g/day) than those individuals with normal weight (171.1 ± 14.9 μg/day) (p < 0.01). The major food source of vitamin K are vegetables (45.35% of the intake comes from this food group), followed by fats and oils (13.28%), pulses (11.69%), meat (10.62%), cereals (5.33%) and fruits (4.60%). Meeting adequate intake for vitamin K is favoured by the increase in the consumption of vegetables (OR 0.329; CI95%: 0.279, 0.387), dairy (OR 0.815; CI95%: 0.690, 0.963), pulses (OR 0.091; CI95%: 0.054, 0.154) and fruits (OR 0.774; CI95%: 0.677, 0.885) (p < 0.001). A positive correlation was found between vegetable consumption and the intake of vitamin K (r = 0.432, p < 0.001). Adults with an inadequate intake of vitamin K have a lower consumption of vegetables (2.04 ± 1.16 servings/day) than adults with adequate intake (3.78 ± 1.65 servings/day) (p < 0.001).. The intake of vitamin K was lower than adequate intake in a significant percentage of the Spanish population (30.2%), which highlights the need to increase the consumption of vegetables, the major source of the vitamin (which are consumed in insufficient amount, by the 49.6% of the studied population), and to improve the diet as a whole, monitoring the intake of vitamin K, in order to obtain a nutritional and health benefit.

Topics: Adolescent; Adult; Diet Surveys; Feeding Behavior; Female; Humans; Male; Middle Aged; Nutrition Surveys; Nutritional Status; Spain; Vitamin K; Vitamin K Deficiency; Young Adult

Topics: Humans; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Determine the prevalence of fat-soluble vitamin deficiency in children with cystic fibrosis (CF) aged ≤18 years in New South Wales (NSW), Australia, from 2007 to 2010.. A retrospective analysis of fat-soluble vitamin levels in children aged ≤18 years who lived in NSW and attended any of the three paediatric CF centres from 2007 to 2010. An audit of demographic and clinical data during the first vitamin level measurement of the study period was performed.. Deficiency of one or more fat-soluble vitamins was present in 240/530 children (45%) on their first vitamin level test in the study period. The prevalence of vitamins D and E deficiency fell from 22.11% in 2007 to 15.54% in 2010, and 20.22% to 13.89%, respectively. The prevalence of vitamin A deficiency increased from 11.17% to 13.13%. Low vitamin K was present in 29% in 2007, and prevalence of prolonged prothrombin time increased from 19.21% to 22.62%. Fat-soluble vitamin deficiency is present in 10%-35% of children with pancreatic insufficiency, but only a very small proportion of children who are pancreatic-sufficient.. This is one of few studies of fat-soluble vitamin deficiency in children with CF in Australia. Fat-soluble vitamin testing is essential to identify deficiency in pancreatic-insufficient children who may be non-compliant to supplementation or require a higher supplement dose, and pancreatic-sufficient children who may be progressing to insufficiency. Testing of vitamin K-dependent factors needs consideration. Further studies are needed to monitor rates of vitamin deficiency in the CF community.

Topics: Adolescent; Age Factors; Avitaminosis; Biomarkers; Child; Child, Preschool; Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Female; Humans; Male; New South Wales; Prevalence; Prothrombin Time; Retrospective Studies; Solubility; Vitamin A; Vitamin A Deficiency; Vitamin D; Vitamin D Deficiency; Vitamin E; Vitamin E Deficiency; Vitamin K; Vitamin K Deficiency; Vitamins

Although vitamin K deficiency has been implicated in adult inflammatory bowel disease (IBD), its prevalence in pediatric IBD remains unknown. We carried out a cross-sectional study in 63 children with Crohn's disease (CD) and 48 with ulcerative colitis (UC) to assess the prevalence of vitamin K deficiency and to search for potential correlation between vitamin K status and pediatric IBD activity. Vitamin K status was assessed using protein induced by vitamin K absence-II (PIVKA-II; ELISA). Prevalence of vitamin K deficiency was 54.0% in CD and 43.7% in UC. Vitamin K deficiency was more common in patients with higher CD activity, in CD patients with higher mass Z-scores, and less common among children with CD treated with infliximab. Relation of vitamin K deficiency to pediatric IBD clinical course and treatment demand further research.

Topics: Adolescent; Antibodies, Monoclonal; Biomarkers; Bone Density; Child; Colitis, Ulcerative; Crohn Disease; Female; Humans; Infliximab; Male; Protein Precursors; Prothrombin; Risk Factors; Severity of Illness Index; Vitamin K; Vitamin K Deficiency

To explore the diagnostic value of protein induced by vitamin K absence or antagonist -II(PIVKA-II) in non-infant with acquired deficiency of vitamin K-dependent coagulation factors(ADVKCF).. PIVKA-II levels were measured by ELISA in 50 patients with ADVKCF on day 0, 3, 7 after vitamin K treatment. Prothrombin time(PT), APTT, FII: C, FVII: C, FIX: C, and FX: C were analyzed simultaneously. Twenty healthy subjects were enrolled as controls.. The average level of PIVKA-II in ADVKCF group was (3.83 ± 1.40)µg/L, while (1.30 ± 0.54) µg/L in the control group (P < 0.05). The PIVKA-II levels on day 0 and 3 did not show significant difference [(3.83 ± 1.40) µg/L vs (3.79 ± 0.66) µg/L, P > 0.05], but decreasing significantly on day 7 compared to the control group(P < 0.05). The PIVKA-II level was (3.78 ± 1.30) µg/L in patients receiving plasma transfusion, while (3.91 ± 1.49)µg/L in no-plasma-transfusion group (P > 0.05). Coagulation factors II, VII, IX and X activity which decreased significantly before treatment returned to normal range after one week use of vitamin K, leading to complete correction of prolonged APTT and PT (>100 seconds).. The PIVKA-II level in ADVKCF patients is significantly higher than that of healthy subjects within one week treatment of vitamin K, which is not influenced by plasma transfusion. This study suggests that PIVKA-II is a more sensitive parameter than APTT, PT and the activity of coagulation factor, which could be a valuable factor in the early diagnosis of ADVKCF.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Child; Child, Preschool; Coagulation Protein Disorders; Female; Humans; Male; Middle Aged; Protein Precursors; Prothrombin; Vitamin K; Vitamin K Deficiency; Young Adult

Newborns are at risk for vitamin K deficiency and subsequent bleeding unless supplemented at birth. Vitamin K deficiency bleeding is an acquired coagulopathy in newborn infants because of accumulation of inactive vitamin K-dependent coagulation factors, which leads to an increased bleeding tendency. Supplementation of vitamin K at birth has been recommended in the United States since 1961 and successfully reduced the risk of major bleeding. Refusal or omission of vitamin K prophylaxis is increasing and puts newborn infants at risk for life-threatening bleeding.. Over an eight month period, we encountered seven infants with confirmed vitamin K deficiency; five of these patients developed vitamin K deficiency bleeding.. The mean age of the seven infants with vitamin K deficiency was 10.3 weeks (range, 7-20 weeks); manifestations ranged from overt bleeding to vomiting, poor feeding, and lethargy. None of the infants had received vitamin K at birth, and all were found to have profound derangement of coagulation parameters, which corrected rapidly with administration of vitamin K in IV or intramuscular form. Four of the seven infants had intracranial hemorrhage; two of these infants required urgent neurosurgical intervention.. Supplementation of vitamin K at birth for all newborns prevents major hemorrhagic complications, such as intracranial bleeding, due to vitamin K deficiency. Parental refusal of vitamin K is increasingly common. It is critical that health care providers and the public be made aware of the varied presentation of this preventable acquired coagulopathy.

Topics: Age of Onset; Brain; Female; Follow-Up Studies; Humans; Infant; Intracranial Hemorrhages; Male; Treatment Refusal; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Humans; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Serum undercarboxylated osteocalcin (ucOC) is an index of vitamin K nutritional status in treatment-naive postmenopausal osteoporotic women. The purpose of the present study was to reveal the association between vitamin K nutritional status and serum ucOC concentrations in postmenopausal osteoporotic women taking bisphosphonates. Eighty-six postmenopausal women with osteoporosis (age range: 47-90 years) initiated bisphosphonate treatment. Vitamin K nutritional status was evaluated using a simple vitamin K-intake questionnaire and serum ucOC concentrations were measured after 6 months of treatment. The patients were divided into two groups according to the simple vitamin K-intake questionnaire score: a low vitamin K-intake (score <40) group (n=67) and a normal vitamin K-intake (score >=40) group (n=19). There were no significant differences between the groups in baseline parameters including age, height, body weight, body mass index, serum alkaline phosphatase (ALP), urinary cross-linked N-terminal telopeptides of type I collagen (NTX), and changes in serum ALP and urinary NTX concentrations during the 6-month treatment period. However, the mean serum ucOC concentration after 6 months of treatment was significantly higher in the low vitamin K-intake group (2.79 ng/mL) than in the normal vitamin K-intake group (2.20 ng/mL). These results suggest that 78% of postmenopausal osteoporotic women treated with bisphosphonates may have vitamin K deficiency as indicated by low vitamin K-intake and high serum ucOC concentrations, despite having a similar reduction in bone turnover to women who have normal vitamin K-intake.. 血清未羧化的骨钙素(ucOC)是治疗初始的绝经后骨质疏松妇女的维生素K 营 养状况的指标。本研究的目的是揭示服用双磷酸盐的绝经后骨质疏松妇女维生 素K 的营养状况和血清ucOC 的浓度之间的关联。86 位绝经后骨质疏松妇女 开始双磷酸盐治疗(年龄范围47-90 岁)。采用简单的维生素K 摄入量调查问卷 评估维生素K 的营养状况，治疗6 个月后测定血清中ucOC 的浓度。根据简单 的维生素K 摄入量调查问卷评分将患者分为两组：低维生素K 摄入组(得分 <40, n=60)和正常维生素K 摄入组(得分>=40, n=19)。两组患者的基线参数包括 年龄、身高、体重、体质指数、血清碱性磷酸酶(ALP)和尿N-末端肽交联的I 型胶原蛋白(NTX)，以及6 个月治疗期间血清ALP 和尿NTX 浓度的变化之间 没有显著差异。然而治疗6 个月之后，低维生素K 摄入组的平均血清ucOC 浓 度(2.79 ng/mL)显著高于正常维生素K 摄入组(2.20 ng/mL)。这些结果表明，尽 管78%用双磷酸盐治疗的绝经后骨质疏松妇女与正常维生素K 摄入量的妇女 有相似的骨转化降低，但从低维生素K 摄入量和高血清ucOC 浓度看出他们可 能缺乏维生素K。

Topics: Aged; Aged, 80 and over; Bone Density Conservation Agents; Diphosphonates; Follow-Up Studies; Humans; Japan; Middle Aged; Nutritional Status; Osteocalcin; Osteoporosis, Postmenopausal; Surveys and Questionnaires; Treatment Outcome; Vitamin K; Vitamin K Deficiency

A 61-year old woman with atrial fibrillation developed macrohaematuria during anticoagulant treatment with a direct oral factor Xa inhibitor for stroke prevention. Abnormal results of coagulation assays were first interpreted as an effect of the anticoagulant. However, upon further testing diagnosis of vitamin K deficiency was established. After vitamin K supplementation, coagulation tests normalized and macrohaematuria disappeared. Treatment with broad spectrum antibiotics for urinary tract infection was finally established as a rare cause for vitamin K deficiency in the patient.

Topics: Administration, Oral; Anti-Bacterial Agents; Anticoagulants; False Positive Reactions; Female; Hematuria; Humans; Middle Aged; Phenprocoumon; Treatment Outcome; Vitamin K; Vitamin K Deficiency

Topics: Canada; Health Education; Home Childbirth; Humans; Infant, Newborn; Midwifery; Parents; Refusal to Participate; Treatment Refusal; Vaccination; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Brain; Female; Humans; Infant; Infant, Newborn; Intracranial Hemorrhages; Male; Parents; Treatment Refusal; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Osteoarthritis is the most common form of arthritis, with knee osteoarthritis being the leading cause of lower extremity disability among older adults in the US. There are no treatments available to prevent the structural pathology of osteoarthritis. Because of vitamin K's role in regulating skeletal mineralization, it has potential to be a preventative option for osteoarthritis. We therefore examined the relation of vitamin K to new-onset radiographic knee osteoarthritis and early osteoarthritis changes on magnetic resonance imaging (MRI).. Subjects from the Multicenter Osteoarthritis (MOST) Study had knee radiographs and MRI scans obtained at baseline and 30 months later, and plasma phylloquinone (vitamin K) measured at baseline. We examined the relationship of subclinical vitamin K deficiency to incident radiographic knee osteoarthritis and MRI-based cartilage lesions and osteophytes, respectively, using log binomial regression with generalized estimating equations, adjusting for potential confounders.. Among 1180 participants (62% women, mean age 62±8 years, mean body mass index 30.1±5.1 kg/m(2)), subclinical vitamin K deficiency was associated with incident radiographic knee osteoarthritis (risk ratio [RR] 1.56; 95% confidence interval [CI], 1.08-2.25) and cartilage lesions (RR 2.39; 95% CI, 1.05-5.40) compared with no deficiency, but not with osteophytes (RR 2.35; 95% CI, 0.54-10.13). Subclinically vitamin K-deficient subjects were more likely to develop osteoarthritis in one or both knees than neither knee (RR 1.33; 95% CI, 1.01-1.75 and RR 2.12; 95% CI, 1.06-4.24, respectively).. In the first such longitudinal study, subclinical vitamin K deficiency was associated with increased risk of developing radiographic knee osteoarthritis and MRI-based cartilage lesions. Further study of vitamin K is warranted given its therapeutic/prophylactic potential for osteoarthritis.

Topics: Aged; Female; Humans; Knee Joint; Longitudinal Studies; Male; Middle Aged; Osteoarthritis, Knee; Radiography; Vitamin K; Vitamin K Deficiency

It has been demonstrated that single nucleotide polymorphism (SNP) (R325Q, 974G>A) in the gamma-glutamyl carboxylase (GGCX) gene is associated with the bone mineral density (BMD). In the present study, we investigated the effect of GGCX polymorphism (974G>A) on the correlations among the vitamin K in-take, level of serum vitamin K, and ratio of undercarboxylated osteocalcin (ucOC) to intact osteocalcin (OC) in healthy young Japanese subjects.. Healthy young adult subjects (n=189) were genotyped for the poly-morphism, and we measured the levels of serum vitamin K, intact OC, ucOC, and dietary nutrient intakes.. Dietary vitamin K intake from vegetables was significantly correlated with the level of serum phylloquinone (PK), and vitamin K intake from fermented beans, natto, was also significantly correlated with the level of serum menaquinone-7 (MK-7). Moreover, the total dietary vitamin K intake showed a significant negative correlation with the ratio of ucOC to intact OC. Interestingly, on grouping by the GGCX genotype, there was a significant interaction between the ratio of ucOC to intact OC with vitamin K intake in homozygotes (GG-type) and heterozygotes (GA-type) (p<0.001). These results suggest that an adequate nutritional strategy is necessary for people with high-risk genotypes (GG- or GA-type).. We demonstrated the effects of SNP (974G>A) in the GGCX gene on the correlation between dietary vitamin K intake and gamma-carboxylation of serum OC. Our data may be useful for planning strategies to prevent osteoporosis.. 前言：γ-麩胺醯羧化酶(GGCX)基因的單核苷酸多型性(SNP)與骨骼礦物質密度 (BMD)之相關性已被證實。本篇研究探討，在日本的健康年輕受試者中，其 GGCX 多型性(974G>A)對於維生素K 攝取、血清中維生素K 濃度和羧化不全骨 鈣素(ucOC)與完整骨鈣素(OC)比值之間關聯性的影響。方法：共有189 位健康 年輕成人進行基因多型性檢測，並測量其血清中維生素K、OC、ucOC 濃度和 飲食中營養素攝取量。結果：飲食中攝取來自蔬菜的維生素K 與血清中維生素 K1(PK；葉綠醌)有顯著相關；而攝取來自發酵豆類-納豆的維生素K 也與血清中 維生素K2(MK-7；甲萘醌-7)有顯著相關。此外，從飲食中攝取的總維生素K 和 ucOC 與OC 比值有顯著負相關。值得注意的是，將GGCX 基因型分組時發現， 同型結合子(GG-type)和異型結合子(GA-type)兩組的ucOC 與OC 比值和維生素 K 攝取有顯著交互作用(p<0.001)。以上結果顯示，適當的營養策略對於具有高 風險基因型(GG-或GA-type)的人是必要的。結論：本研究證實GGCX 基因中的 SNP(974G>A)多型性對於飲食維生素K 攝取與血清骨鈣素γ-羧化相關性之效 應。本資料對於規劃預防骨質疏鬆症之策略也許會有幫助。

Topics: Carbon-Carbon Ligases; Diet; Genotype; Humans; Japan; Male; Nutritional Status; Osteocalcin; Polymorphism, Single Nucleotide; Soy Foods; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency; Young Adult

Topics: Aged; Aged, 80 and over; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Palliative Care; Pilot Projects; Treatment Outcome; Vitamin K; Vitamin K Deficiency

Serum undercarboxylated osteocalcin (s-ucOC) is a marker for vitamin K metabolism (deficiency). The aim of this study was to investigate the serum levels of ucOC in patients with bilateral knee osteoarthritis (K-OA), and the correlation between ucOC and other biomarkers for K-OA. A total of 25 patients (22 women, 3 men, mean age 76.0±7.8, range 54-88 years, mean BMI 24.9±4.7) with a Kellgren-Lawrence grade of 3 or 4 for bilateral knee were enrolled in this study. The levels of s-ucOC and other biomarkers were measured. The levels of s-ucOC (5.66±4.70 ng/ml) as well as other cartilage metabolism markers, were elevated in the patients; however, bone metabolism markers were within the normal ranges. Of interest, there was a significant correlation between s-ucOC and serum hyaluronan (a marker for synovitis) (P<0.05). Our findings suggest that vitamin K metabolism may be associated with synovitis in patients with K-OA, and s-ucOC could be a biomarker for K-OA.

Topics: Aged; Aged, 80 and over; Biomarkers; Cartilage; Female; Humans; Hyaluronic Acid; Knee Joint; Male; Middle Aged; Osteoarthritis, Knee; Osteocalcin; Vitamin K; Vitamin K Deficiency

  The aim of this study was to compare maternal and infant characteristics by mode of VK administration..   De-identified computerised birth files of all babies born in New South Wales (NSW), Australia between January 2007 and December 2009 (when VK prophylaxis was measured) were included in the present study. The outcome variable, mode of VK prophylaxis, was recorded by checkbox as oral, IM injection, none or not stated..   We analysed population-based birth data from 2007 to 2009 in NSW, Australia and found that IM injection was the most prevalent mode of administration (96.3%, n = 263, 555), followed by oral (2.6%, n = 7023) and none (1.2%, n = 3136). Compared to neonates receiving IM VK, those with oral or none were more likely to have vaginal births without medical interventions at birth centres or planned home births and were less likely to receive hepatitis B vaccination. Among neonates administered oral VK, a larger proportion were preterm births and breastfed at discharge compared to neonates administered VK as an IM injection. Neonates with no VK recorded were more likely to be admitted to neonatal intensive care, but may have received VK later in the birth admission..   A small proportion of the Australian neonates may be at risk of inadequate protection from VKBD due to parental concerns about the safety of IM injection of VK to neonates.

Topics: Administration, Oral; Adult; Female; Humans; Infant; Infant, Newborn; Injections, Intramuscular; Mothers; New South Wales; Risk Factors; Vitamin K; Vitamin K Deficiency; Young Adult

Extrahepatic biliary atresia (EHBA) is a rare disease characterized by progressive and obliterative cholangiopathy in infants and is one of the major causes of secondary vitamin K deficiency bleeding (VKDB) due to cholestasis-induced fat malabsorption. Breast feeding increases the tendency of bleeding in EHBA patients because breast milk contains low amounts of vitamin K. A 2-month-old female infant unexpectedly died, with symptoms of vomiting and jaundice prior to death. She had been born by uncomplicated vaginal delivery and exhibited normal growth and development with breastfeeding. There was no history of trauma. She received vitamin K prophylaxis orally. In an emergency hospital, a CT scan showed a right intracranial hematoma and mass effect with midline shift to the left. In the postmortem examination, severe atresia was observed in the whole extrahepatic bile duct. Histologically, cholestasis, periductal fibrosis, and distorted bile ductules were noted. The gallbladder was not identified. A subdural hematoma and cerebellar tonsillar herniation were found; however, no traumatic injury in any part of the body was observed. Together, these findings suggest that the subdural hemorrhage was caused by secondary vitamin K deficiency resulting from a combination of cholestasis-induced fat malabsorption and breastfeeding. Subdural hemorrhage by secondary VKDB sometimes occurs even when vitamin K prophylaxis is continued. This case demonstrated that intrinsic factors, such as secondary VKDB (e.g., EHBA, neonatal hepatitis, chronic diarrhea), should also be considered in infant autopsy cases presenting with subdural hemorrhage.

Topics: Bile Ducts, Extrahepatic; Biliary Atresia; Cholestasis, Extrahepatic; Encephalocele; Female; Fibrosis; Forensic Pathology; Hematoma, Subdural; Humans; Infant; Liver Cirrhosis; Vitamin K; Vitamin K Deficiency; Vitamins

Available evidence suggests that patients with short bowel syndrome (SBS) might be at risk of vitamins A, D, E and B(1) deficiency. However, there is little clinical data describing the vitamin K status. Therefore, in the present study we aimed to assess the body resources of vitamin K in a subset of SBS patients.. The study comprised 33 patients aged 1 month to 16 years. PIVKA-II concentrations were determined in all subjects.. In all studied subjects, coagulation parameters were normal. PIVKA-II levels indicative of vitamin K deficiency was found in 3 (9.1%) SBS patients. One patient had been receiving an additional intravenous vitamin K dose of 5 mg/week. In all SBS patients with cirrhosis and cholestasis, PIVKA-II concentrations were low (<2 ng/ml). However, all patients with severe liver disease were receiving vitamin K several times a month.. Vitamin K deficiency may appear in SBS patients.

Topics: Adolescent; Antifibrinolytic Agents; Biomarkers; Blood Coagulation; Child; Child, Preschool; Cholestasis; Female; Humans; Infant; Liver Cirrhosis; Male; Protein Precursors; Prothrombin; Short Bowel Syndrome; Vitamin K; Vitamin K Deficiency; Vitamins

A 53 year old female who was maintained on long-term warfarin therapy due to history of pulmonary embolism, repeatedly presents with an abnormally prolonged Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT). After many asymptomatic episodes were corrected with Vitamin K therapy to temporarily reverse the effects of the warfarin, the cause of the apparent coagulopathy was further investigated. Factor Activity Assays of the common pathway factors II, IX, and X all revealed critically low values; below the threshold even a loading dose of warfarin is typically capable of eliciting. The patient tested strongly positive for Tissue Transglutaminase IgA, which is highly suggestive of a gluten-sensitive enteropathy. One effect of this condition is malabsorption due to flattened intestinal villi. The patient was determined to have an acquired vitamin K deficiency secondary to gluten-sensitive enteropathy. Her condition was exacerbated by the long-term warfarin therapy, resulting in the prolonged PT and PTT. The patient was treated with vitamin K therapy, which reversed the deficiency and corrected her abnormal coagulation results.

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Celiac Disease; Drug Hypersensitivity; Female; Humans; International Normalized Ratio; Middle Aged; Partial Thromboplastin Time; Prothrombin Time; Treatment Outcome; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Adolescent; Adult; Aged; Blood Coagulation Disorders; Blood Coagulation Factors; Case-Control Studies; Child; Female; Humans; Male; Middle Aged; Retrospective Studies; Vitamin K; Vitamin K Deficiency; Young Adult

We report a case of fat-soluble vitamin deficiency in a 14-year old boy who had chronic duodenal obstruction. He presented with periodic unexplained bleeding tendency. The laboratory results showed positive fat globules in stool and prolonged prothrombin time. His further investigation revealed low plasma vitamin A and undetectable plasma vitamin E. After parenteral vitamin K and oral vitamin A and E supplement, these abnormalities resolved although he still had absent knee jerk. We propose that fat malabsorption and fat-soluble vitamin deficiency can occur after prolonged duodenal obstruction that induce bacterial overgrowth following by bile acid deconjugation. Despite very few case reports, screening for fat malabsorption and fat-soluble vitamin deficiency might be warranted in patients with chronic small bowel obstruction.

Topics: Adolescent; Delayed Diagnosis; Duodenal Obstruction; Gastric Bypass; Hemorrhage; Humans; Infusions, Parenteral; Male; Postoperative Complications; Reoperation; Steatorrhea; Treatment Outcome; Vitamin K; Vitamin K Deficiency

Vitamin K is essential for activation of γ-carboxyglutamate (Gla)-proteins including the vascular calcification inhibitor matrix Gla-protein (MGP). Insufficient vitamin K intake leads to production of uncarboxylated, mostly inactive proteins and contributes to an increased cardiovascular risk. In kidney transplant recipients, cardiovascular risk is high but vitamin K intake and status have not been defined. We investigated dietary vitamin K intake, vascular vitamin K status and its determinants in kidney transplant recipients. We estimated vitamin K intake in a cohort of kidney transplant recipients (n = 60) with stable renal function (creatinine clearance 61 [42-77] (median [interquartile range]) ml/min), who were 75 [35-188] months after transplantation, using three-day food records and food frequency questionnaires. Vascular vitamin K status was assessed by measuring plasma desphospho-uncarboxylated MGP (dp-ucMGP). Total vitamin K intake was below the recommended level in 50% of patients. Lower vitamin K intake was associated with less consumption of green vegetables (33 vs 40 g/d, p = 0.06) and increased dp-ucMGP levels (621 vs 852 pmol/L, p<0.05). Accordingly, dp-ucMGP levels were elevated (>500 pmol/L) in 80% of patients. Multivariate regression identified creatinine clearance, coumarin use, body mass index, high sensitivity-CRP and sodium excretion as independent determinants of dp-ucMGP levels. In a considerable part of the kidney transplant population, vitamin K intake is too low for maximal carboxylation of vascular MGP. The high dp-ucMGP levels may result in an increased risk for arterial calcification. Whether increasing vitamin K intake may have health benefits for kidney transplant recipients should be addressed by future studies.

Topics: Aged; Calcium-Binding Proteins; Diet; Diet Surveys; Extracellular Matrix Proteins; Female; Humans; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Linear Models; Male; Matrix Gla Protein; Middle Aged; Multivariate Analysis; Vitamin K; Vitamin K Deficiency; Vitamins

Topics: Anticoagulants; Heart Diseases; Humans; International Normalized Ratio; Nutritional Requirements; Pulmonary Embolism; Thrombophlebitis; Vitamin K; Vitamin K Deficiency

Pseudoxanthoma elasticum (PXE) is a heritable multisystem disorder manifesting with ectopic calcification of peripheral connective tissues, caused by mutations in the ABCC6 gene. Alterations in vitamin K metabolism have been suggested to contribute to the pathomechanisms of the mineralization process. In this study we administered vitamin K or its glutathione conjugate (K3-GSH) into Abcc6 (-/-) mice which recapitulate features of PXE. Oral administration of vitamin K2 in dosages, which vastly exceed the amounts in control diet or the recommended amounts for humans, did not alter the ectopic mineralization in Abcc6 (-/-) mice. Similarly, intravenous administration of K3-GSH did not alter the degree of mineralization. Testing of vitamin K2, K3 and K3-GSH in an in vitro calcification system provided no evidence of mineralization inhibition. Collectively, our data suggest that vitamin K deficiency in the peripheral tissues is not a simple explanation for development of mineral deposits in PXE.

Topics: Animals; ATP-Binding Cassette Transporters; Calcinosis; Cell Line; Disease Models, Animal; Elastic Tissue; Female; Humans; Male; Mice; Mice, Knockout; Multidrug Resistance-Associated Proteins; Mutation; Pseudoxanthoma Elasticum; Vitamin K; Vitamin K Deficiency

In Japan, γ-carboxylation of blood coagulation factors is the basis for determining adequate intake (AI) for vitamin K in Dietary Reference Intakes (DRIs) issued in 2010. Recently, vitamin K is also known to be essential for preventing fracture. In this study, relative susceptibility of liver and bone to vitamin K deficiency was studied. Thirty-seven elderly institutionalized subjects were evaluated for vitamin K status by measuring serum PIVKA (protein induced by vitamin K absence) -II and ucOC (undercarboxylated osteocalcin) levels, as sensitive markers for hepatic and skeletal vitamin K deficiency, respectively. Serum PIVKA-II and ucOC levels, with their cut-off values in the parentheses, were 20.2±8.9 mAUmL (28 mAU/mL) and 4.7±3.0 ng/mL (4.5 ng/mL), respectively. Median vitamin K intake was approximately 200 μg/day, which is more than 3 times higher than the current Japanese AI. Vitamin K intake was significantly correlated with serum PIVKA-II and ucOC/OC levels, but not with serum ucOC level. Although serum ucOC level is generally a good indicator for vitamin K status, multiple regression analysis revealed that elevated bone turnover marker significantly contributed to serum ucOC level. All subjects had vitamin K intake exceeding AI for vitamin K. Nevertheless, serum PIVKA-II and ucOC concentrations exceeded the cut-off value in 14% and 43% of subjects, respectively. The present findings suggest that vitamin K intake greater than the current AI is required for the skeletal health in the institutionalized elderly.

Topics: Aged; Aged, 80 and over; Biomarkers; Bone and Bones; Diet; Elder Nutritional Physiological Phenomena; Energy Intake; Female; Fractures, Bone; Homes for the Aged; Humans; Liver; Liver Diseases; Male; Nursing Homes; Osteocalcin; Protein Precursors; Prothrombin; Vitamin K; Vitamin K Deficiency

Topics: Adolescent; Carbon-Carbon Ligases; Coagulation Protein Disorders; DNA Mutational Analysis; Humans; Male; Mutation; Phenotype; Vitamin K; Vitamin K Deficiency

In 1980, the first nationwide survey on late vitamin K deficiency bleeding (VKDB) in infants was conducted in Japan, and it was followed by the second, third and fourth nationwide surveys in 1985, 1988 and 1991, respectively. The fifth nationwide survey was designed to ascertain the epidemiology of late VKDB between January 1999 and December 2004.. Questionnaires were sent to 2161 hospitals in Japan that employed members of the Japan Pediatric Society in March 2005. Responses were received from 1373 hospitals, for a response rate of 63.5%.. The total number of reported cases was 71, including 21 idiopathic type and 16 secondary type. The incidence of late VKDB was estimated to be 1.9 cases per 100,000 births (95% confidence interval: 1.2-3.0) during this survey period. In 34 cases, the presence or absence of any underlying disease was not clarified. A total of 67/71 infants were entirely breast-fed. Intracranial hemorrhaging was observed in 26 (63.4%) out of 41 infants whose bleeding sites were described in the questionnaires. In 63 cases (88.7%) of late VKDB found in the present survey, however, vitamin K had been given at least once either during or after the neonatal period.. A reevaluation of the current prophylaxis strategy for late VKDB in infants is necessary.

Topics: Antifibrinolytic Agents; Humans; Incidence; Infant, Newborn; Japan; Prognosis; Surveys and Questionnaires; Survival Rate; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Vitamin K-deficiency can cause haemorrhage in newborns and infants from the first hours up to several months after birth. These 'vitamin K deficiency bleedings' (VKDB) can be divided into 3 forms: early (occur in the first hours after birth), classic (first week after birth) and late (between the 2nd and the 12th week of life). The current Dutch vitamin K practice guideline consists of prophylactic administration of 1 mg vitamin K orally directly after birth and a daily dose of 25 μg from day 8 onwards. The current prophylactic treatment provides good protection against VKDB for healthy, breastfed infants. However, the current prophylactic treatment provides insufficient protection for a specific group of infants, namely breastfed infants with defective fat absorption (in cholestasis), leading to less efficient absorption of vitamin K by the body. Anually approximately 5 infants from this group suffer serious haemorrhage. After evaluation of current literature and advice from The Health Council of the Netherlands, vitamin K dosage was adapted for all breastfed infants from day 8 to 3 months (12th week of life) following birth: the daily dose was raised from 25 µg to 150 µg per day.

Topics: Antifibrinolytic Agents; Breast Feeding; Dose-Response Relationship, Drug; Humans; Incidence; Infant, Newborn; Netherlands; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Dietary Supplements; Humans; Vegetables; Vitamin K; Vitamin K Deficiency

Individuals with celiac disease (CD) are predisposed to a number of haematological abnormalities including anaemia secondary to malabsorption of iron, vitamin B12 or folate; anaemia of chronic disease and coagulopathy secondary to vitamin K deficiency. Correction of coagulopathy with vitamin K is necessary before endoscopic biopsy in patients with suspected CD. However, vitamin K causes haemolysis in glucose-6 phosphate-dehydrogenase deficiency.. When vitamin K administration becomes necessary for correction of coagulopathy in patients with CD; glucose-6 phosphate-dehydrogenase deficiency should be considered.

Topics: Celiac Disease; Contraindications; Diet, Gluten-Free; Endoscopy, Gastrointestinal; Glucosephosphate Dehydrogenase; Glucosephosphate Dehydrogenase Deficiency; Hemolysis; Humans; Infant; Intestinal Mucosa; Male; Vitamin K; Vitamin K Deficiency

Vitamin K, vitamin K-dependent proteins, and vitamin D may be involved in the regulation of calcification in chronic kidney disease (CKD).. Vitamin K and D status was measured as dietary intake, plasma phylloquinone, serum percent uncarboxylated osteocalcin (%ucOC), proteins induced by vitamin K absence (PIVKA-II), Vitamin K Epoxide Reductase single-nucleotide polymorphism, apolipoprotein E genotype, and plasma 25-hydroxyvitamin D (25(OH)D) in 172 subjects with stage 3 to 5 CKD. Nutritional status was determined by subjective global assessment.. Subclinical vitamin K deficiency criteria was met by 6% (phylloquinone), 60% (%ucOC), and 97% (PIVKA-II) of subjects, whereas 58.3% and 8.6% had 25(OH)D insufficiency and deficiency, respectively. Dietary vitamin K intake was associated with higher phylloquinone and lower PIVKA-II. There were positive correlations between phylloquinone and the presence of stable weight, and the absence of subcutaneous fat loss or muscle wasting. 25(OH)D levels were positively associated with stable weight and albumin (P < 0.001). PIVKA-II levels were associated with apolipoprotein E genotype. Higher %ucOC and lower 25(OH)D were similarly associated with CKD stage, parameters of mineral metabolism, and urine albumin to creatinine ratio.. These data indicate that a suboptimal vitamin K and D status is prevalent in patients with CKD. Sufficiency of both vitamins K and D was similarly predicted by measures of overall improved nutritional status. Proteinuria was associated with both a suboptimal vitamin D status as well as worse peripheral vitamin K status.

Topics: Adult; Aged; Aged, 80 and over; Apolipoproteins E; Biomarkers; Chronic Disease; Cross-Sectional Studies; Diet; Female; Genetic Markers; Genotype; Humans; Kidney Diseases; Linear Models; Male; Middle Aged; Mixed Function Oxygenases; Nutritional Status; Osteocalcin; Polymorphism, Single Nucleotide; Protein Precursors; Proteinuria; Prothrombin; Vitamin D; Vitamin D Deficiency; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Vitamin K Epoxide Reductases; Young Adult

Soft-tissue mineralization is a tightly regulated process relying on the activity of systemic and tissue-specific inhibitors and promoters of calcium precipitation. Many of these, such as matrix gla protein (MGP) and osteocalcin (OC), need to undergo carboxylation to become active. This post-translational modification is catalyzed by the gammaglutamyl carboxylase GGCX and requires vitamin K (VK) as an essential co-factor. Recently, we described a novel phenotype characterized by aberrant mineralization of the elastic fibers resulting from mutations in GGCX. Because of the resemblance with pseudoxanthoma elasticum (PXE), a prototype disorder of elastic fiber mineralization, it was coined the PXE-like syndrome. As mutations in GGCX negatively affect protein carboxylation, it is likely that inactive inhibitors of calcification contribute to ectopic mineralization in PXE-like syndrome. Because of the remarkable similarities with PXE, we performed a comparative study of various forms of VK-dependent proteins in serum, plasma (using ELISA), and dermal tissues (using immunohistochemistry) of PXE-like and PXE patients using innovative, conformation-specific antibodies. Furthermore, we measured VK serum concentrations (using HPLC) in PXE-like and PXE samples to evaluate the VK status. In PXE-like patients, we noted an accumulation of uncarboxylated Gla proteins, MGP, and OC in plasma, serum, and in the dermis. Serum levels of VK were normal in these patients. In PXE patients, we found similar, although not identical results for the Gla proteins in the circulation and dermal tissue. However, the VK serum concentration in PXE patients was significantly decreased compared with controls. Our findings allow us to conclude that ectopic mineralization in the PXE-like syndrome and in PXE results from a deficient protein carboxylation of VK-dependent inhibitors of calcification. Although in PXE-like patients this is due to mutations in the GGCX gene, a deficiency of the carboxylation co-factor VK is at the basis of the decreased activity of calcification inhibitors in PXE.

Topics: Adult; Aged; Animals; Calcinosis; Calcium-Binding Proteins; Extracellular Matrix Proteins; Humans; Matrix Gla Protein; Mice; Mice, Knockout; Middle Aged; Mixed Function Oxygenases; Mutation; Proteins; Pseudoxanthoma Elasticum; Syndrome; Vitamin K; Vitamin K Deficiency; Vitamin K Epoxide Reductases

Delayed haemorrhage due to vitamin K deficiency in early infancy has rarely been the cause of acquired hemostatic disorders. We report here 11 cases of vitamin K deficiency bleeding (VKDB), despite receiving appropriate dosage of injectible vitamin K at birth. Bleeding symptoms ranged from excessive bleed from cuts to intracranial bleed. Tuberculosis, diarrhea with intermittent antibiotic therapy were some of the associated symptoms. Laboratory tests confirmed acquired bleeding diathesis due to vitamin K deficiency, which was corrected after adequate vitamin K supplementation. VKDB is not an uncommon phenomenon and should be considered in the differential diagnosis of a child with bleeding diathesis.

Topics: Diarrhea; Humans; Infant; Retrospective Studies; Tuberculosis; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

For children and adolescents with cystic fibrosis (CF) and pancreatic insufficiency, the efficacy of routine vitamin K supplementation to normalize vitamin K status remains unclear.. This study examined and determined predictors of vitamin K status in subjects aged 8-25 y with CF and pancreatic insufficiency taking various vitamin K supplements.. In 97 subjects, serum 25-hydroxyvitamin D [25(OH)D], dietary intake, vitamin K supplement intake, and vitamin K statusmdashdetermined on the basis of the percentage of serum undercarboxylated osteocalcin (%ucOC; sufficient: lt 20%) and plasma proteins induced by vitamin K absence-factor II (PIVKA-II; n = 60; sufficient: le 2 microg/L)mdashwere assessed. The vitamin K supplementation groups were as follows: lt 150 microg/d (low; multivitamins or no supplement), 150-999 microg/d (middle; CF-specific vitamins), and ge 1000 microg/d (high; mephyton). %ucOC values were compared with 140 healthy subjects aged 6-21 y.. In subjects with CF, the median (range) %ucOC was 35% (3%, 76%) and the median (range) for PIVKA-II was 2 (0, 42) micro g/L. Subjects with CF had a higher %ucOC with low [45% (10%, 76%)] and medium [41% (3%, 66%)] supplement intakes but not with a high supplement intake [16% (4%, 72%)] compared with healthy subjects [23% (0%, 43%); both P lt 0.05]. Supplementation group for males and females and 25(OH)D and age for males were significant predictors of vitamin K status.. Vitamin K status was often suboptimal despite routine supplementation. Only subjects taking high-dose vitamin K achieved a status similar to healthy subjects, and only the vitamin K supplementation dose predicted vitamin K status for males and females. These data suggest that higher doses of vitamin K are required.

Topics: Adolescent; Case-Control Studies; Child; Cystic Fibrosis; Dietary Supplements; Female; Humans; Male; Nutritional Status; Osteocalcin; Pancreatic Diseases; Prothrombin; Sex Factors; Vitamin D; Vitamin K; Vitamin K Deficiency; Vitamins; Young Adult

Topics: Adolescent; Child; Cystic Fibrosis; Humans; Pancreatic Diseases; Vitamin K; Vitamin K Deficiency; Vitamins; Young Adult

Topics: Animals; Antineoplastic Agents; Diet; Humans; Neoplasms; Risk Factors; Vitamin K; Vitamin K Deficiency; Vitamins

Dietary vitamin K is known to influence the anticoagulation response to warfarin. It is possible that dietary vitamin K availability also influences the pharmacological activity of other oral anticoagulants, which target the vitamin-K dependent clotting proteins in the coagulation cascade. This study examined whether vitamin K insufficiency affected anticoagulation response to the direct thrombin inhibitor, ximelagatran. Anticoagulation response to ximelagatran and warfarin in rats on a normal diet was compared to those on a vitamin K deficient diet. Ximelagatran and warfarin increased prothrombin time (PT) by 1.4- and 1.3-fold, activated partial thromboplastin time (APTT) by 1.8- and 1.4-fold and ecarin clotting time (ECT) by 6.8- and 1.2-fold, respectively, in rats on normal diet. Vitamin K deficient diet alone caused modest increases in PT, APTT and ECT. The anticoagulant activity of both ximelagatran and warfarin was significantly greater in rats on vitamin K deficient diet (6.1- and 12.3-fold for PT, 2.6- and 5.1-fold for APTT and 2.9- and 1.6-fold for ECT, respectively) compared to those on normal diet. Factor II activity was reduced by both ximelagatran (58%) and warfarin (44%) in rats on normal diet. However, factor II activity was virtually abolished (<0.1%) by both drugs in rats on vitamin K deficient diet. The results suggest that oral anticoagulant drugs, whose primary site of action is not within the vitamin K cycle, may also exhibit variability in clinical response due to dietary variation as the established coumarin drugs such as warfarin.

Topics: Animals; Anticoagulants; Azetidines; Benzylamines; Enzyme Inhibitors; Male; Rats; Rats, Wistar; Thrombin; Vitamin K; Vitamin K Deficiency

We report the case of a 6-week-old female who presented an intracranial hemorrhage due to late vitamin K deficiency bleeding (VKDB). No other evident bleeding sites were present at the moment of diagnosis. Intramuscular vitamin K (1 mg) was administered at birth. She was exclusively breast-fed. No other risk factors for VKDB were detected. Low levels of vitamin K-dependent coagulation factors and their normalization after vitamin K administration confirmed the diagnosis of late VKDB. The present case suggests potential risks related to a single dose of intramuscular vitamin K at birth.

Topics: Age of Onset; Antifibrinolytic Agents; Female; Humans; Infant, Newborn; Injections, Intramuscular; Intracranial Hemorrhages; Treatment Outcome; Vitamin K; Vitamin K Deficiency

Topics: Administration, Oral; Animals; Anticoagulants; Azetidines; Benzylamines; Biological Availability; Blood Coagulation; Drug Design; Factor Xa Inhibitors; Food-Drug Interactions; Humans; Rats; Thrombin; Vitamin K; Vitamin K Deficiency

Congenital combined deficiency of the vitamin K-dependent coagulation factors is a rare bleeding disorder caused by either a defect in the gamma-glutamyl carboxylase or the vitamin K epoxide reductase enzyme complex. The diagnosis should be considered when vitamin-K dependent factor activities are decreased and liver dysfunction, vitamin K deficiency, and factitious coumarin ingestion have been excluded. We report a case of VKCFD in a child resulting from compound heterozygosity for two novel splice site mutations of the gamma-glutamyl carboxylase gene. Oral vitamin K supplementation resulted in partial resolution of proteins and complete resolution of bleeding.

Topics: Blood Coagulation Factors; Carbon-Carbon Ligases; Child; Coagulation Protein Disorders; Diagnosis, Differential; Humans; Male; Mixed Function Oxygenases; Munchausen Syndrome; Mutation; Polymorphism, Single Nucleotide; Vitamin K; Vitamin K Deficiency; Vitamin K Epoxide Reductases

In Texas, apprentice midwives do not have prescriptive authority to administer parenteral vitamin K. This case report underscores the importance of parenteral vitamin K administration in preventing vitamin K deficiency bleeding and the potential danger in prohibiting apprentice midwives from providing this standard of care to the newborn.

Topics: Antifibrinolytic Agents; Brain Death; Humans; Infant; Injections, Intramuscular; Intracranial Hemorrhages; Male; Midwifery; Texas; Vitamin K; Vitamin K Deficiency

The study objective was to validate a semi-quantitative food frequency questionnaire (FFQ) specifically designed to measure dietary vitamin K intake. A 50-item FFQ was interviewer-administered and compared with data previously obtained from 5-day food records. Thirty-nine community-dwelling healthy men and women aged 65 to 85 years were recruited from the Montréal metropolitan area. Absolute and relative agreements between methods were assessed. Vitamin K intake measured by the vitamin K FFQ (mean+/-standard deviation; 222+/-186 microg/day) was significantly higher than that obtained by food records (135+/-153 microg/day; P<0.001). Bland-Altman analysis on log(10)-transformed data indicated that vitamin K intake from vitamin K FFQ was 2.26 times (95% confidence interval: 1.90 to 2.67) higher than food records, limits of agreement ranging from 0.80 to 6.35. However, correlation between methods was strong and highly significant (r=0.83; P<0.001). Cross-classification also showed that 72% of participants were correctly classified into thirds and only 8% were grossly miscategorized. Weighted kappa value (kappa=0.60) also indicated a good relative agreement. In light of these results, the vitamin K FFQ is a valid tool for ranking individuals according to their vitamin K intake. The poor absolute agreement likely results from the inability for food records to adequately measure the usual intake of episodically consumed foods, particularly those high in vitamin K. The vitamin K FFQ will be useful in large-scale, population-based research on vitamin K and disease as well as in clinical practice, especially that focusing on anticoagulant therapy.

Topics: Aged; Aged, 80 and over; Antifibrinolytic Agents; Diet Records; Female; Geriatric Assessment; Humans; Male; Nutrition Assessment; Nutritional Requirements; Quebec; Reproducibility of Results; Sensitivity and Specificity; Surveys and Questionnaires; Vitamin K; Vitamin K Deficiency

In rare cases, severe fetal vitamin K deficiency bleeding may occur in utero as a result of insufficient vitamin K placental transfer. We present a case of a 32-week-preterm infant born with severe intracranial hemorrhage to a pregnant woman who suffered from hyperemesis gravidarum. Neonatal hematologic status was compatible with vitamin K deficiency whereas the maternal coagulation function was normal. This case emphasizes the potential risk of fetal bleeding owing to vitamin K deficiency in pregnancies complicated with hyperemesis gravidarum. These women should be closely monitored and vitamin K prophylaxis might be considered.

Topics: Adult; Antifibrinolytic Agents; Female; Fetal Diseases; Gestational Age; Humans; Hyperemesis Gravidarum; Infant, Newborn; Intracranial Hemorrhages; Male; Pregnancy; Pregnancy Trimester, Third; Vitamin K; Vitamin K Deficiency

There are various ways to prevent late vitamin K deficiency bleeding in exclusively breast-fed infants. The French paediatric society recommends weekly doses of 2mg of mixed micellar preparation of vitamin K during the entire period of exclusive breastfeeding, i.e. 24 doses for a period of six months, which matches recommendations for optimal duration of exclusive breastfeeding by the French paediatric society, WHO and AAP. This significantly exceeds recommendations in other European countries. We describe the risks of vitamin K deficiency; we provide a review of recent literature about administrating vitamin K in other countries, and give a recommendation for daily practice that seems to be acceptable. Nevertheless, a comprehensive randomised prospective study is needed in France to answer the question of the best ways of preventing vitamin K deficiency bleeding.

Topics: Breast Feeding; Dietary Supplements; Humans; Infant; Vitamin K; Vitamin K Deficiency; Vitamins

Topics: Animals; Blood Coagulation; Cardiomyopathies; Diagnostic Errors; Hemorrhage; Mice; Reverse Transcriptase Inhibitors; Vitamin K; Vitamin K Deficiency

Topics: Blood Coagulation; Blood Proteins; Humans; Vitamin K; Vitamin K Deficiency

Des-gamma-carboxy prothrombin (DCP) is an abnormal prothrombin, increased in serum of patients with hepatocellular carcinoma (HCC) as result of an acquired defect of post-translational carboxylation of prothrombin's precursor. It is unclear if the reduced activity of gamma-carboxylase is secondary to vitamin K deficiency or to an altered gene encoding this enzyme. The aim of this study was to evaluate the effect of vitamin K administration on DCP and alpha-fetoprotein (AFP) levels, to identify a relationship between vitamin K and DCP serum levels and to investigate mechanisms of serum elevation of DCP levels.. The authors determined DCP and AFP serum levels and vitamin K concentration in 64 cirrhotics with HCC and in 60 cirrhotic subjects without HCC. In HCC subjects DCP and AFP levels were measured before and after vitamin K administration. A t-test for unpaired data was applied (P values <0.05 statistically significant).. Only HCC patients had detectable levels of DCP and significant AFP levels. Administration of vitamin K reduced DCP but not AFP levels in HCC patients. No correlation was observed between vitamin K concentration and DCP levels: vitamin K concentration was similar both in HCC patients and in control group without HCC; HCC patients had the same vitamin K concentration regardless of elevated o reduced DCP levels after vitamin K administration.. DCP detectable serum levels are the result not only of vitamin K deficiency or selective defects of carboxylase, because probably alterations of membrane receptors or cytoplasmatic transfers, that are necessary for the function of vitamin K, are involved.

Topics: Aged; alpha-Fetoproteins; Biomarkers; Carcinoma, Hepatocellular; Case-Control Studies; Female; Humans; Injections, Intravenous; Liver Neoplasms; Male; Middle Aged; Protein Precursors; Prothrombin; Up-Regulation; Vitamin K; Vitamin K 1; Vitamin K Deficiency

A man was admitted with abdominal pain. Treatment for acute diverticulitis was instituted with intravenous antibiotics and oral limitation. Imaging demonstrated a complex inflammatory mass. Prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen were within normal limits. However, repeat preoperative clotting studies demonstrated a severe unexpected coagulopathy to have developed since admission that could have caused fatal intraoperative exsanguination. Direct assays showed severe, isolated deficiency of vitamin K dependent clotting factors, and mixing studies normalised both the PT and APTT, ruling out a coagulation inhibitor. The coagulopathy responded to intravenous vitamin K administration. Dietary insufficiency underlies vitamin K deficiency in the presence of normal biliary and enteral function. A significant coagulopathy can result with additional eradication of intestinal microflora. Hypoprothombinaemia is recognised as a consequence of protracted treatment with broad spectrum antibiotics, and vigilance is required for those at risk. The development of such a rapid and unexpected coagulopathy posed a complex preoperative management issue delaying operative intervention; although avoided by fortuitous preoperative screening, it could have caused significant intraoperative bleeding. The remarkably specific lack of vitamin K dependent clotting factors strongly suggested a vitamin K deficiency and administration of coumarins was ruled out.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Antifibrinolytic Agents; Diverticulitis; Humans; Hypoprothrombinemias; Male; Vitamin K; Vitamin K Deficiency

Late hemorrhagic disease of the newborn (HDN) presents 0.5-6 months after birth with mucocutaneous and intracranial bleeding. We describe here two cases of late HDN in infants who received vitamin K. The first case is a previously healthy breastfed male who received one dose of oral vitamin K at birth and developed an intracranial hemorrhage 5 weeks later. He was treated with intravenous vitamin K and recombinant factor VIIa prior to emergent craniectomy. An unrelated infant presented at 5 months of age with diarrhea and easy bruising despite IM vitamin K at birth. These cases illustrate the morbidity associated with late HDN.

Topics: Factor VIIa; Humans; Infant; Infant, Newborn; Male; Recombinant Proteins; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding; Vitamins

Topics: Adult; Female; Fetal Diseases; Gestational Age; Humans; Hydrocephalus; Hyperemesis Gravidarum; Intracranial Hemorrhages; Parenteral Nutrition, Total; Pregnancy; Ultrasonography, Prenatal; Vitamin K; Vitamin K Deficiency

Topics: Health Education; Humans; Infant Welfare; Infant, Newborn; Nurse's Role; Parents; Public Opinion; United Kingdom; Vitamin K; Vitamin K Deficiency

Dietary dosing of the non-nucleoside reverse transcriptase inhibitor (NNRTI) TMC125, under development for treatment of HIV-1, resulted in a syndrome in male mice in a previous experiment that was termed hemorrhagic cardiomyopathy. In literature, this syndrome, which was described in rodent species only, was linked to vitamin K deficiency. Two mechanistic studies were conducted, one with dietary administration and a second with gavage. The syndrome was reproduced in only 1 male mouse after continuous dietary dosing, and TMC125 was demonstrated to affect coagulation parameters (prothrombin time [PT], activated partial thromboplastin time [APTT], clotting factors II, VII and XI), particularly in males. This was counteracted by vitamin K supplementation, supporting the hypothesis that the effects were mediated via a vitamin K deficiency. It is therefore concluded that the observed cardiac changes were not caused by a direct cardiotoxic effect but occurred after a state of disabled clotting ability with subsequent effects on mouse cardiac muscle. Therefore, clotting times can be used as adequate safety biomarkers in clinical trials. To date, no changes have been observed at therapeutic doses of TMC125, following human monitoring of PT and APTT. One other NNRTI, Efavirenz (Sustiva), has been reported to cause prolongation of coagulation times in rats and monkeys.

Topics: Administration, Oral; Animals; Area Under Curve; Blood Coagulation; Cardiomyopathies; Diet; Female; Heart; Hemorrhagic Disorders; Male; Mice; Nitriles; Partial Thromboplastin Time; Prothrombin Time; Pyridazines; Pyrimidines; Reverse Transcriptase Inhibitors; Troponin T; Vitamin K; Vitamin K Deficiency

Newborns routinely receive vitamin K to prevent vitamin K deficiency bleeding. The efficacy of oral vitamin K administration may be compromised in infants with unrecognized cholestasis. We aimed to compare the risk of vitamin K deficiency bleeding under different prophylactic regimens in infants with biliary atresia.. From Dutch and Danish national biliary atresia registries, we retrieved infants who were either breastfed and received 1 mg of oral vitamin K at birth followed by 25 microg of daily oral vitamin K prophylaxis (Netherlands, 1991-2003), 2 mg of oral vitamin K at birth followed by 1 mg of weekly oral prophylaxis (Denmark, 1994 to May 2000), or 2 mg of intramuscular prophylaxis at birth (Denmark, June 2000-2005) or were fed by formula. We determined the absolute and relative risk of severe vitamin K deficiency and vitamin K deficiency bleeding on diagnosis in breastfed infants on each prophylactic regimen and in formula-fed infants.. Vitamin K deficiency bleeding was noted in 25 of 30 of breastfed infants on 25 microg of daily oral prophylaxis, in 1 of 13 on 1 mg of weekly oral prophylaxis, in 1 of 10 receiving 2 mg of intramuscular prophylaxis at birth, and in 1 of 98 formula-fed infants (P < .001). The relative risk of a bleeding in breastfed compared with formula-fed infants was 77.5 for 25 microg of daily oral prophylaxis, 7.2 for 1 mg of weekly oral prophylaxis, and 9.3 for 2 mg of intramuscular prophylaxis at birth.. A daily dose of 25 microg of vitamin K fails to prevent bleedings in apparently healthy infants with unrecognized cholestasis because of biliary atresia. One milligram of weekly oral prophylaxis offers significantly higher protection to these infants and is of similar efficacy as 2 mg of intramuscular prophylaxis at birth. Our data underline the fact that event analysis in specific populations at risk can help to evaluate and improve nationwide prophylactic regimens.

Topics: Administration, Oral; Biliary Atresia; Breast Feeding; Confidence Intervals; Denmark; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Gestational Age; Hemorrhage; Humans; Infant, Newborn; Injections, Intramuscular; Logistic Models; Male; Netherlands; Primary Prevention; Prothrombin; Registries; Risk Assessment; Statistics, Nonparametric; Treatment Outcome; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Child, Preschool; History, 20th Century; Humans; Infant; Infant, Newborn; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Brodifacoum, also known as a superwarfarin, is a four-hydroxycoumarin derivative. It exerts an anticoagulant effect by inhibiting the reduction of vitamin K-2,3 epoxide, thereby decreasing the production of vitamin K-dependent clotting factors. It is a readily available rodenticide that has been associated with accidental ingestions in children. We report the case of a 21-year-old male who was admitted to the hospital with spontaneous bruising, hematuria and abdominal pain secondary to a perinephric hematoma. The patient was found to have a markedly prolonged prothrombin time and activated partial thromboplastin time that corrected with mixing of normal plasma. He had a normal factor V level; however, factors VII and X were less than 1% and factors II and IX were between 2% and 4% of normal. Ingestion of an anticoagulant was suspected, although the patient denied intentional or accidental ingestion. He was treated with FEIBA (Factor VIII Inhibitor Bypass Activity), fresh frozen plasma and oral vitamin K. The patient was stabilized and discharged from the hospital on oral vitamin K 50 mg twice daily. A serum brodifacoum level was later found to be markedly elevated at 320 ng/ml. We followed the brodifacoum level, which decreased to 31 ng/ml approximately six weeks after initial presentation. The exact length of treatment required to prevent recurrence of the coagulopathy was not determined because the patient did not return for follow-up. Superwarfarin ingestion must be suspected and quickly identified in patients with depletion of vitamin K-dependent clotting factors resulting in potentially catastrophic bleeding.

Topics: 4-Hydroxycoumarins; Adult; Blood Coagulation Disorders; Blood Coagulation Factors; Humans; Male; Plasma; Rodenticides; Treatment Outcome; Vitamin K; Vitamin K Deficiency

Vitamin K is an important co-factor in the production of proteins that inhibit vascular calcification. A low dietary Vitamin K intake has been associated with aortic and coronary calcifications and an elevated cardiovascular risk. Calcifications in the arteries of the breasts have also been associated with cardiovascular risk, but whether there is a relation with a low Vitamin K intake has not yet been studied.. We conducted a cross-sectional study among 1689 women, aged 49-70 years. Dietary Vitamins K1 and K2 intake was calculated from a validated food frequency questionnaire. Breast arterial calcifications (BAC) were assessed on standard screening mammograms by two independent radiologists. With a general linear model mean Vitamins K1, K2 and Vitamin K2 subtypes were calculated for women with BAC and without, adjusted for age, smoking, diabetes, intake of saturated fat, mono-unsaturated fat, poly-unsaturated fat and protein- and calcium-intake.. BAC was less common in the highest (9%) quartile of Vitamin K2 intake, compared to the lowest (13%) (OR 0.7, 95% CI 0.5-1.1) and not different across quartiles of Vitamin K1 intake. Mean Vitamin K2 levels and mean levels of Vitamin K2 subtypes MK-5 through MK-10 were lower in the participants with BAC (p=0.01) compared to participants without BAC. However, after adjustment for aging, smoking, diabetes and dietary factors the association of mean Vitamin K2 intake with BAC was no longer significant.. Calcifications in breast arteries are not associated with a lower dietary intake of Vitamin K.

Topics: Aged; Calcinosis; Cross-Sectional Studies; Diet Records; Europe; Female; Humans; Mammary Arteries; Mammography; Middle Aged; Nutritional Status; Prospective Studies; Vascular Diseases; Vitamin K; Vitamin K Deficiency

Topics: Administration, Oral; Hemothorax; Humans; Infant, Newborn; Male; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Despite administration of vitamin K (VK), some infants show lower activity of VK-dependent coagulation factors and they could develop intracranial hemorrhage. For preventing VK deficiency bleeding (VKDB) in infants, oral administration of VK and a screening test for VK deficiency are carried out in Japan. For the screening, the total activity of VK-dependent coagulation factors is measured using a commercial product, Normotest. This study was undertaken to clarify the importance of the following genetic and environmental factors on the coagulation status in one-month-old infants: two polymorphisms in the factor VII gene, -323P0/10 (a 10-bp insertion in the promoter region at position -323) and R353Q (the replacement of arginine [R] with glutamine [Q] at residue 353) and sex, age, gestational age, birth weight, and feeding regimen. Two hundred Japanese infants (34.6 +/- 4.0 days old) were screened for VK-dependent coagulation activity with Normotest and were genotyped for the two polymorphisms. Among the subjects screened, 18 infants (9%) carried the P10 allele and 26 (13%) carried the R353Q allele. Multiple regression analysis showed that the 10-bp inserted (P10) allele or the Q allele was associated with the lower coagulation activities. The coagulation activities for the R/Q genotype were significantly lower than those for the R/R genotype and those for the P0/P10 genotype were significantly lower than those for the P0/P0 genotype. Therefore, infants who carry the P10 allele or the Q allele show lower activity of VK-dependent coagulation factors. These infants may have a higher risk of VKDB manifestation.

Topics: Birth Weight; Blood Coagulation; Blood Coagulation Factors; Blood Coagulation Tests; Body Weight; Bottle Feeding; Breast Feeding; Factor VII; Female; Gene Frequency; Genotype; Gestational Age; Humans; Infant; Infant, Newborn; Male; Polymorphism, Genetic; Regression Analysis; Sex Factors; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: 4-Hydroxycoumarins; Adult; Anticoagulants; Diagnosis, Differential; Epistaxis; Female; Hematemesis; Humans; Partial Thromboplastin Time; Pesticides; Poisoning; Prothrombin Time; Thrombosis; Unconsciousness; Vitamin K; Vitamin K Deficiency

Topics: Antifibrinolytic Agents; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Pregnancy; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

To conduct and report monitoring of vitamin K deficiency bleeding (VKDB) in Great Britain and Ireland following the 1988-90 survey (VKDB-90).. Two 2-year surveys conducted during 1993-4 (VKDB-94) and 2001-02 (VKDB-02).. Data collected from all consultant paediatricians in Great Britain and Ireland.. All infants presenting with bleeding resulting from vitamin K (VK) deficiency.. Incidence of VKDB, related mortality/morbidity and VK prophylaxis recommended/received, noting predisposing features.. Compared with previous studies, VKDB-02 found fewer cases of VKDB (RR: 0.27 (95% CI: 0.12 to 0.59), p<0.001) with no deaths, no long-term morbidity and reduced incidence among those receiving any oral dosing (RR: 0.24 (95% CI: 0.06 to 1.01), p<0.059). Breast-fed infants accounted for the vast majority of cases. The number receiving no prophylaxis fell consecutively over time: 20 of 27 in VKDB-90, 10 of 32 in VKDB-94 and 4 (because of parental refusal) of 7 in VKDB-02. Seven received one oral dose of VK in VKDB-90, 16 in VKDB-94 and none in VKDB-02. Underlying liver disease was found in six cases in VKDB-90, 12 in VKDB-94 and one in VKDB-02.. In the most recent survey, the incidence of VKDB was about one third that in the two earlier studies. Late onset VKDB remains virtually confined to breast-fed infants who have received either no VK or just one oral dose. The effectiveness of oral prophylaxis regimens has improved over the last 15 years, but parental refusal of prophylaxis has become more problematic.

Topics: Age of Onset; Antifibrinolytic Agents; Birth Weight; Breast Feeding; Health Surveys; Humans; Incidence; Infant; Infant, Newborn; Ireland; Liver Diseases; Male; Prospective Studies; Sex Distribution; United Kingdom; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Vitamin K has been known to regulate bone formation through osteocalcin synthesis by osteoblasts, which is important for mineralization and bone structure. The mechanism underlying the relationship of vitamin K with the changes of microanatomy is not fully understood, and our goal is to test whether bone deformities develop in association with vitamin K deficiency. Fish were fed a semi-purified diet containing either devoid (0.00 mg/kg diet) or adequate (40.0 mg/kg diet supplemented but 20.8 mg/kg analyzed) levels of vitamin K (menadione sodium bisulphite) for 20 weeks. At the end of 8 and 20 weeks, fish were subjected to gross examination and X-ray, and mineral content of the vertebrae was measured. The vertebrae were also subjected to histological, histomorphometric and enzyme histochemical examinations to determine the bone formation and resorption. Vitamin K deficiency primarily decreased bone mineralization and subsequently a decrease in bone mass thus resulted in an increased susceptibility to bone deformity. The occurrence of bone deformities coincided with an increased amount of osteoid tissue and decreased bone mineral content. Number of osteoblasts and osteoclasts were not affected by dietary vitamin K. In conclusion, vitamin K deficiency can impair bone mineralization and enhances bone deformities.

Topics: Animals; Bone Resorption; Calcification, Physiologic; Dietary Supplements; Fishes; Osteoclasts; Osteogenesis; Radiography; Spine; Vitamin K; Vitamin K Deficiency

Since vitamin K2 (VitK2) syrup prophylaxis has become a routine measure for neonates and young infants, the incidence of vitamin K deficiency (VitK-D) in infancy has markedly decreased. However, we recently experienced 2 infantile cases of VitK deficiency, in whom intracranial hemorrhage (ICH) was the first clinical sign of CMV hepatitis. Case 1 is a breast-fed boy who received VitK2 syrup orally at birth and at the age of 1 month. He did not suckle well and developed a generalized tonic convulsion twice at the age of 8 weeks. Case 2 is a mixed-fed boy who also received VitK2 syrup twice but developed vomiting and drowsiness at the age of 4 months. In both cases, laboratory tests showed anemia, leukocytosis, liver dysfunction with cholestasis, and coagulopathy, consistent with VitK-D abnormality. Their serological analyses showed that cytomegalovirus (CMV) IgG and IgM were both positive. In case 1, CMV DNA was positive, as judged by the PCR method. In case 2, CMV antigenemia was positive. Hence we diagnosed these two patients as having VitK-D ICH caused by CMV hepatitis with cholestasis. CMV hepatitis is a risk factor of VitK-D ICH.

Topics: Cholestasis, Intrahepatic; Cytomegalovirus; Cytomegalovirus Infections; Hepatitis, Viral, Human; Humans; Infant; Intracranial Hemorrhages; Male; Radionuclide Imaging; Vitamin K; Vitamin K Deficiency

Superwarfarins are widely used as rodenticides. They are similar to warfarin, but they are more potent and act longer. In case of poisoning, they cause severe bleeding, usually from multiple sites.. A 67-yr-old man was admitted with melaena, epistaxis and haemarthrosis in his left knee. PT, INR and aPTT were markedly increased. Initially, the patient was treated with blood and fresh frozen plasma (FFP) transfusions. However at the second day, PT, INR and aPTT were even worse. The combination of persistent coagulopathy, normal mixing studies, normal liver function tests and absence of hepatic failure or malabsorption syndromes lead to the suspicion of vitK dependent clotting factors deficiency due to superwarfarin poisoning. Indeed, the patient admitted a suicide attempt with rodenticide, although he had previously denied it. Psychiatric evaluation revealed a disturbed personality. Melaena stopped after 7 d. Then, the patient was administered 30 mg of vitK daily for a total period of 4 months.. Superwarfarin poisoning leads to severe bleeding, usually from multiple sites. Prolonged treatment with high doses of vitK is necessary. Haemarthrosis, as a complication of superwarfarin poisoning, is presented here for the first time in literature.

Topics: 4-Hydroxycoumarins; Aged; Blood Coagulation Tests; Hemarthrosis; Hemorrhage; Humans; Male; Rodenticides; Vitamin K; Vitamin K Deficiency

In this study, clinical and demographic features of 16 cases with late vitamin K deficiency bleeding are presented. Ages of infants were between 30 and 130 days. Their delivery histories were uneventful, and family histories for bleeding disorders were negative. All parents except one were unaware of whether their children received vitamin K at birth or not. All cases did not have any underlying illness to explain the abnormal coagulation profile. The common presenting finding was pallor (62.5%). Intracranial haemorrhage was the most common bleeding site (37.5%), and two patients (12.5%) died because of it. Late vitamin K deficiency bleeding is still an important handicap in infants. Parents and healthcare providers should be informed about the importance of vitamin K prophylaxis to prevent vitamin K deficiency in infants.

Topics: Blood Coagulation Tests; Cerebral Hemorrhage; Female; Humans; Infant; Male; Pallor; Retrospective Studies; Turkey; Vitamin K; Vitamin K Deficiency; Vitamins

The present study characterizes the anticoagulant resistance mechanism in a Danish bromadiolone-resistant strain of Norway rats (Rattus norvegicus), with a Y139C VKORC1 mutation. We compared liver expression of the VKORC1 gene, which encodes a protein of the vitamin K 2,3-epoxide reductase complex, the NQO1 gene, which encodes a NAD(P)H quinone dehydrogenase and the Calumenin gene between bromadiolone-resistant and anticoagulant-susceptible rats upon saline and bromadiolone administration. Additionally, we established the effect of bromadiolone on the gene expression in the resistant and susceptible phenotype. Bromadiolone had no effect on VKORC1 and NQO1 expression in resistant rats, but induced significantly Calumenin expression in the susceptible rats. Calumenin expression was similar between the resistant and the susceptible rats upon saline administration but twofold lower in resistant rats after bromadiolone treatment. These results indicate that Danish bromadiolone resistance does not involve an overexpression of calumenin. Independent of the treatment, we observed a low VKORC1 expression in resistant rats, which in conjugation with the Y139C polymorphism most likely explains the low VKOR activity and the enhanced need for vitamin K observed in Danish resistant rats. Furthermore the bromadiolone resistance was found to be associated with a low expression of the NQO1 gene.

Topics: 4-Hydroxycoumarins; Animals; Anticoagulants; Calcium-Binding Proteins; Carboxylic Acids; Drug Resistance; Feeding Behavior; Female; Gene Expression Profiling; Gene Expression Regulation; Liver; Male; Mixed Function Oxygenases; NAD(P)H Dehydrogenase (Quinone); Rats; Rats, Mutant Strains; Vitamin K; Vitamin K Deficiency; Vitamin K Epoxide Reductases

This study examined the prevalence of vitamin K deficiency in children pre-bone marrow transplantation (BMT). Vitamin K status was measured by the PIVKA-II assay and prothrombin times. Blood samples were obtained before vitamin-containing TPN was infused. Results indicated that eight of 26 patients (31%) were vitamin K deficient; four cases were attributed to drug antagonism (phenytoin) and four were due to inadequate vitamin K intake, synthesis or malabsorption. Only one patient had a prolonged prothrombin time. Prothrombin time, in our study, is shown to be an ineffective screening tool to determine vitamin K status. All patients receiving phenytoin and chemotherapy are at increased risk of vitamin K deficiency.

Topics: Adolescent; Anticonvulsants; Bone Marrow Transplantation; Child; Child, Preschool; Drug Antagonism; Female; Humans; Infant; Male; Neoplasms; Phenytoin; Prevalence; Prothrombin Time; Retrospective Studies; Risk Factors; Vitamin K; Vitamin K Deficiency

Topics: Aged, 80 and over; Anti-Bacterial Agents; Blood Coagulation; Blood Coagulation Factors; Blood Component Transfusion; Cefoperazone; Female; Hematuria; Humans; Infusions, Intravenous; Plasma; Vitamin K; Vitamin K Deficiency

Children with chronic liver disease are at risk for vitamin K deficiency because of fat malabsorption and inadequate dietary intake. The objective of this study was to determine the prevalence of vitamin K deficiency in children with mild to moderate chronic cholestatic and noncholestatic liver disease.. Vitamin K status was examined in 43 children (0.25-15.9 years) with mild to moderate chronic cholestatic liver disease, 29 children (0.9-16.9 years) with chronic mild to moderate noncholestatic liver disease, and in 44 healthy children (1-18 years). Vitamin K status was assessed by the plasma PIVKA-II (protein induced in vitamin K absence) assay (enzyme-linked immunosorbent assay). Plasma PIVKA-II values greater than 3 ng/mL are indicative of vitamin K deficiency.. The mean plasma PIVKA-II (+/-SD) in cholestatic, noncholestatic, and healthy children was 61.9 +/-144, 1.2 +/- 3, and 2.1 +/- ng/mL, respectively (P < 0.002). Fifty-four percent of the children supplemented with vitamin K had plasma PIVKA-II greater than 3 ng/mL. Plasma conjugated bilirubin, total bile acids, and severity of liver disease were positively correlated with plasma PIVKA-II levels (P < 0.05).. Vitamin K deficiency is prevalent in children with mild to moderate chronic cholestatic liver disease, even with vitamin K supplementation. Elevated PIVKA-II levels occurred in children with a normal prothrombin, indicating that more sensitive markers of vitamin K status should be used in children with chronic liver disease. Vitamin K deficiency was related to degree of cholestasis and severity of liver disease in children. Children without cholestasis did not exhibit vitamin K deficiency.

Topics: Adolescent; Case-Control Studies; Child; Child, Preschool; Cholestasis, Intrahepatic; Chronic Disease; Dietary Fats; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infant; Liver Diseases; Malabsorption Syndromes; Male; Nutritional Status; Prevalence; Risk Factors; Severity of Illness Index; Vitamin K; Vitamin K Deficiency

Vitamin K deficiency is associated with low bone mineral density and increased risk of bone fracture. Phylloquinone (K1) and menaquinone 4 (MK-4) and 7 (MK-7) are generally observed in human plasma; however, data are limited on their circulating concentrations and their associations with bone metabolism or with gamma-carboxylation of the osteocalcin molecule.. The objectives were to measure the circulating concentrations of K1, MK-4, and MK-7 in women and to ascertain whether each form of vitamin K is significantly associated with bone metabolism.. Plasma concentrations of K1, MK-4, MK-7, undercarboxylated osteocalcin (ucOC; measured by using the new electrochemiluminescence immunoassay), intact osteocalcin (iOC), calcium, and phosphorus; bone-derived alkaline phosphatase activity; and concentrations of urinary creatinine, N-terminal telopeptide, and deoxypyridinoline were measured in healthy women (n = 396).. On average, MK-7 and MK-4 were the highest and lowest, respectively, of the 3 vitamers in all age groups. K1 and MK-7 correlated inversely with ucOC, but associations between nutritional basal concentration of MK-4 and ucOC were not observed. Multiple regression analysis indicated that not only K1 and MK-7 concentrations but also age were independently correlated with ucOC concentration and the ratio of ucOC to iOC. The plasma K1 or MK-7 concentration required to minimize the ucOC concentration was highest in the group aged > or =70 y, and it decreased progressively for each of the younger age groups.. The definite role of ucOC remains unclear. However, if submaximal gamma-carboxylation is related to the prevention of fracture or bone mineral loss, circulating vitamin K concentrations in elderly people should be kept higher than those in young people.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Aging; Biomarkers; Bone and Bones; Bone Density; Carboxylic Acids; Female; Fractures, Bone; Humans; Japan; Middle Aged; Nutritional Requirements; Nutritional Status; Osteocalcin; Risk Factors; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency; Vitamins

Topics: Antifibrinolytic Agents; Child; Hemorrhage; Humans; Injections, Intramuscular; Vitamin K; Vitamin K Deficiency

Vitamin K (K) is an essential factor for the posttranslational modification of blood coagulation factors as well as proteins in the bone matrix (Gla proteins). It is known that K is not only distributed in the liver and bones but also abundantly distributed in the brain, kidney, and gonadal tissues. However, the role of K in these tissues is not well clarified. In this study, we used DNA microarray and identified the genes whose expression was affected in the testis under the K-deficient (K-def) state. The expression of genes involved in the biosynthesis of cholesterol and steroid hormones was decreased in the K-def group. The mRNA levels of Cyp11a - a rate-limiting enzyme in testosterone synthesis - positively correlated with the menaquinone-4 (MK-4) concentration in the testis. Moreover, as compared to the control (Cont) and K-supplemented (K-sup) groups, the K-def group had decreased testosterone concentrations in the plasma and testis. These results suggested that K is involved in steroid production in the testis through the regulation of Cyp11a.

Topics: Alkyl and Aryl Transferases; Animals; Carboxy-Lyases; Cholesterol Side-Chain Cleavage Enzyme; Down-Regulation; Farnesyltranstransferase; Hydroxymethylglutaryl CoA Reductases; Intramolecular Transferases; Male; Oligonucleotide Array Sequence Analysis; Rats; Testis; Testosterone; Vitamin K; Vitamin K Deficiency

The aim of this study was to assess vitamin K status in an unselected population of children with cystic fibrosis (CF) and to investigate any vitamin K effect on bone turnover and bone mineral status.. Children > or =5 years of age who were attending the CF unit were invited to enter the study. Fasting blood samples were analyzed for levels of vitamin K1 and prothrombin produced in vitamin K absence; total, undercarboxylated, and carboxylated osteocalcin (OC); and bone-specific alkaline phosphatase and procollagen I carboxy-terminal propeptide (bone formation markers). Levels of N-telopeptide and free pyridinoline and deoxypyridinoline (bone breakdown products) were measured in urine samples. Bone mineral density and bone mineral content were measured at the lumbar spine and for the total body with a GE Lunar Prodigy densitometer. Statistical analyses were performed with Minitab version 9.1.. One hundred six children entered the study. Sixty-five of 93 children (70%) from whom blood samples were obtained showed suboptimal vitamin K status, on the basis of low serum vitamin K1 levels, increased prothrombin produced in vitamin K absence levels, or both abnormalities. Vitamin K1 levels showed a significant negative correlation with undercarboxylated OC levels but showed no significant correlation with any marker of bone turnover or measurement of bone mineral status. Undercarboxylated OC levels were correlated significantly with bone turnover markers, which themselves showed a significant negative correlation with measurements of bone mineral density and content. There were no significant correlations between carboxylated or undercarboxylated OC levels and bone density measurements.. Vitamin K1 deficiency is common among children with CF, and routine supplements should be considered. Through its role in the carboxylation of OC, vitamin K deficiency may be associated with an uncoupling of the balance between bone resorption and bone formation. A cause-effect relationship between vitamin K deficiency and low bone mass has not been proved.

Topics: Absorptiometry, Photon; Alkaline Phosphatase; Biomarkers; Bone Density; Bone Remodeling; Child; Cystic Fibrosis; Humans; Osteocalcin; Prothrombin; Vitamin K; Vitamin K 1; Vitamin K Deficiency

The common bile duct-ligated (CBDL) rat, which is widely used as a model of human cirrhosis, rapidly develops secondary biliary cirrhosis (SBC) within 4 weeks. The CBDL rat shows poor viability, however, a detailed examination of the causes of its death has not been made. In this study, we investigated the outcome of bile duct ligation in detail and attempted to extend the life span of this model by feeding the animals a diet supplemented with nutrients. Survival rate, blood chemistry, blood cell counts, plasma levels of K vitamins and liver histology were compared among CBDL rats fed a standard diet and an enriched diet. Sham-operated rats were used as a control. Six out of 18 CBDL rats fed the standard diet died within 32 days of operation. The cause of death was massive internal hemorrhage in various organs or body cavities. All CBDL rats fed the enriched diet survived more than 31 days, but the viability of CBDL rats was not significant between those fed the standard diet and the enriched diet. The degree of anemia correlated significantly with the prolongation of prothrombin time. Plasma vitamin K1 levels in CBDL rats were significantly lower than those in sham-operated rats, but vitamin K2 levels were similar. We suggest that massive hemorrhage, which was the direct cause of death, is caused by the impairment of hemostasis resulting from vitamin K deficiency. The enriched diet with vitamin K nutritional supplements seemed to contribute to the prolongation of the life span of CBDL rats.

Topics: Animals; Disease Models, Animal; Hemorrhage; Hemostasis; Ligation; Liver Cirrhosis, Biliary; Male; Rats; Rats, Sprague-Dawley; Survival Rate; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

Biliary atresia (BA) is occasionally diagnosed in infants whose first symptom is a bleeding disorder, such as intracranial bleeding, nasal bleeding or gastrointestinal bleeding. The authors describe 3 cases in which a bleeding disorder was the first symptom of BA. The presenting symptom was intracranial bleeding in a male on day 55 after birth, nasal bleeding in a female at 65 days, and gastrointestinal bleeding in a female at 25 days. Coagulation studies revealed a vitamin K deficiency in all patients. After the administration of vitamin K, the results of coagulation tests normalized and the bleeding tendency of the infants ceased. Subsequently, BA was suspected to be the cause of these bleeding disorders based on imaging findings. BA should therefore be considered in all infants with sudden onset of a tendency to bleed.

Topics: Biliary Atresia; Cholangiography; Female; Hematoma, Subdural; Humans; Infant; Liver Transplantation; Male; Subarachnoid Hemorrhage; Vitamin K; Vitamin K Deficiency

A 25-year-old man presented with macroscopic haematuria associated with a body mass index of 20 kg/m and a severe coagulopathy consistent with vitamin K deficiency. The diagnosis of a profound malabsorption syndrome secondary to coeliac disease was confirmed by small bowel histology and positive coeliac serology.

Topics: Abdominal Pain; Adult; Celiac Disease; Cheilitis; Diagnosis, Differential; Duodenum; Hematuria; Humans; Irritable Bowel Syndrome; Male; Treatment Outcome; Vitamin K; Vitamin K Deficiency; Vomiting

Oral or parenteral administration of vitamin K is the accepted practice for prevention of early vitamin K deficiency bleeding (VKDB) in the newborn. However, vitamin K prophylaxis in the newborn continues to be a worldwide health concern, particularly in breastfed infants. This paper reviews the current status of the use of vitamin K for the prevention of early and late VKDB.

Topics: Humans; Infant Formula; Infant, Newborn; Infant, Premature; Vitamin K; Vitamin K Deficiency

Osteocalcin is a vitamin K dependent protein requiring vitamin K as a cofactor for the enzyme gamma glutamyl carboxylase which converts the glutamate residues at 17, 21, 24 position of the molecule into gamma carboxyglutamate or Gla residues. The carboxylation makes immature osteocalcin or undercarboxylated osteocalcin (ucOC) into mature osteocalcin which enhances calcium binding in bone. The level of undercarboxylated osteocalcin is recognized as a marker of vitamin K2 bone. The level of undercarboxylated osteocalcin is recognized as a marker of vitamin K2 in blood necessary for this process. Mature osteocalcin has a higher affinity for hydroxyapatite than undercarboxylated osteocalcin. Foreign studies have shown that ucOC level is increased in elderly women and postmenopausal women in comparison with young, healthy, reproductive women and level of ucOC is also the marker to predict the risk of hip fracture. The standard value of undercarboxylated osteocalcin in Thai women is not available. The aim of the present study was to find the level of ucOC in reproductive Thai females. 357 healthy female volunteers who had regular menstruation, 20-50 years of age, average age 38.5 years old. The volunteers had no intake of any kind of medicine affecting bone metabolism before blood examination. The mean value of undercarboxylated osteocalcin is 2.69 ng/ml, median is 2.10_ng/ml standard deviation = 2.02,_standard error = 0.107 with 95% confident interval = 2.485 to 2.906 ng/ml. In the authors previous pilot study in elderly and postmenopausal women, the authors found that the mean of ucOC in Thai elderly and postmenopausal women was higher than that of reproductive women.

Topics: Adult; Biomarkers; Female; Humans; Immunoenzyme Techniques; Middle Aged; Osteocalcin; Reference Values; Thailand; Vitamin K; Vitamin K Deficiency

Topics: Hemorrhagic Disorders; Humans; Infant; Infant, Newborn; Male; Respiratory Distress Syndrome, Newborn; Ultrasonography; Vitamin K; Vitamin K Deficiency

Topics: Carcinoma, Hepatocellular; Humans; Liver Cirrhosis; Liver Neoplasms; Vitamin K; Vitamin K 2; Vitamin K Deficiency

Topics: Humans; Vitamin K; Vitamin K Deficiency

Topics: Adult; Blood Coagulation Tests; Celiac Disease; Duodenum; Hemorrhagic Disorders; Humans; Male; Treatment Outcome; Vitamin K; Vitamin K Deficiency

Topics: Atropine; Child; Coagulation Protein Disorders; Dexamethasone; Eye Injuries; Humans; Hyphema; Intraocular Pressure; Male; Partial Thromboplastin Time; Prothrombin Time; Visual Acuity; Vitamin K; Vitamin K Deficiency; Wounds, Nonpenetrating

Vitamin K deficiency is known to cause coagulopathy and bleeding in patients on prolonged antibiotic therapy. This study was conducted to evaluate the status of vitamin K deficiency in hospitalized children on prolonged antibiotic therapy and its role in reversing the coagulopathy. A prospective non-randomized study was conducted on children on antibiotic therapy at a tertiary care hospital. Children in the 1 month-1 year age group developed significant coagulopathy as compared to other age groups. Coagulation abnormalities were also seen to be more in children with greater grades of malnutrition, on a more prolonged course of antibiotics and in children who were critically ill in intensive care. Hypoprothrombinemia previously reported to be due to B-lactam antibiotics containing the N-Methyl Thio Tetrazole (NMTT) group also resulted from antibiotics without this side chain. Inhibition of intestinal microorganisms by antibiotics was thought to be a likely explanation of this phenomenon. We suggest Vitamin K prophylaxis in severely ill patients, on extended periods of antibiotics and inadequate diet to prevent morbidity and mortality.

Topics: Anti-Bacterial Agents; Antifibrinolytic Agents; Child; Child, Preschool; Hospitalization; Humans; Hypoprothrombinemias; Infant; Lactams; Prospective Studies; Treatment Outcome; Vitamin K; Vitamin K Deficiency

To determine whether the use of mixed micellar vitamin K improves the efficacy of the 3 x 2 mg oral vitamin K prophylaxis schedule.. Nationwide active surveillance for vitamin K deficiency bleeding (VKDB) complemented with two surveys on the use of the mixed micellar preparation in hospitals and by paediatricians.. Infants in Germany in 1997-2000.. Prophylaxis with three oral doses of 2 mg mixed micellar vitamin K.. Confirmed VKDB between day 8 and week 12 and no condition requiring specific vitamin K supplementation known before the onset of bleeding.. Twenty nine reports met the case definition: seven had not received any vitamin K prophylaxis; for three, vitamin K prophylaxis was unknown; two had insufficient vitamin K prophylaxis for their age; 17 had been given the recommended doses. The mixed micellar preparation had been given to seven, other preparations to nine, and one had been given both. These cases did not differ with respect to the site of bleeding and cholestasis detected at bleeding. Estimates of the use of the mixed micellar preparation in birth hospitals and by paediatricians yielded 1 817 769 newborns exposed to the mixed micellar preparation and 1 320 926 newborns exposed to other preparations. The rate of late VKDB was 0.44/100 000 (95% confidence interval (CI) 0.19 to 0.87) in children given mixed micellar vitamin K compared with 0.76/100 000 (95% CI 0.36 to 1.39) in children given other preparations.. Mixed micellar vitamin K did not significantly improve the efficacy of the 3 x 2 mg oral vitamin K prophylaxis schedule.

Topics: Administration, Oral; Antifibrinolytic Agents; Child, Preschool; Germany; Humans; Infant; Infant, Newborn; Micelles; Population Surveillance; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Vitamin K deficiency in infants can cause life-threatening haemorrhages. To prevent this, neonates in the Netherlands receive an oral dose of 1 mg vitamin K directly after birth. In addition, because breast milk contains little vitamin K, breast-fed infants receive a daily dose of 25 micrograms the first three months. Of three female infants aged 4 weeks, 5 months and 3 months, respectively, two developed an intracranial haemorrhage, which caused death in one. In two cases there were signs of a bleeding tendency, but no tests were done because the patients appeared healthy otherwise. The underlying resorptive disorders, cholestasis and fat malabsorption, caused few symptoms and were discovered only after a vitamin K deficiency bleeding had occurred. In an infant with a bleeding tendency, one should consider the possibility of vitamin K deficiency, even if adequate prophylaxis has been given.

Topics: Antifibrinolytic Agents; Breast Feeding; Cholestasis; Fatal Outcome; Female; Humans; Infant; Infant, Newborn; Intracranial Hemorrhages; Lipid Metabolism, Inborn Errors; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Prevention of early vitamin K deficiency bleeding (VKDB) of the newborn, with onset at birth to 2 weeks of age (formerly known as classic hemorrhagic disease of the newborn), by oral or parenteral administration of vitamin K is accepted practice. In contrast, late VKDB, with onset from 2 to 12 weeks of age, is most effectively prevented by parenteral administration of vitamin K. Earlier concern regarding a possible causal association between parenteral vitamin K and childhood cancer has not been substantiated. This revised statement presents updated recommendations for the use of vitamin K in the prevention of early and late VKDB.

Topics: Administration, Oral; Health Policy; Hemorrhagic Disorders; Humans; Infant, Newborn; Injections, Intramuscular; Leukemia; Recurrence; Vitamin K; Vitamin K Deficiency

Topics: England; Hemorrhage; Humans; Infant, Newborn; Infant, Premature; Neonatology; Surveys and Questionnaires; Vitamin K; Vitamin K Deficiency

To evaluate oral vitamin K prophylaxis at birth by giving 2 mg phytomenadione, followed by weekly oral vitamin K prophylaxis; 1 mg was administered by the parents until 3 mo of age.. A total of 507850 live babies were born in Denmark during the study period, November 1992 to June 2000. Of these infants, 78% and 22% received oral and intra-muscular prophylaxis, respectively; i.e. about 396000 neonates received oral prophylaxis at birth. Weekly oral prophylaxis was recommended for all infants as long as they were mainly breastfed. A survey of possible cases of vitamin K deficiency bleeding (VKDB) was carried out by repeated questionnaires to all Danish paediatric departments and by checking the National Patient Register.. No cases of VKDB were revealed, i.e. the incidence was 0-0.9:100000 (95% CI). The questionnaires were used to evaluate compliance with the regimen. Parents of 274 infants participated. A dose of vitamin K was regarded as having been given if the infant received a drop of vitamin K or was mostly formula-fed that week, and the prophylaxis was regarded as completed if the infant had received at least 9 doses. Compliance was good, with 94% of the infants completing the course of prophylaxis.. Weekly oral vitamin K supplementation during the first 3 mo of life was an efficient prophylaxis against VKBD. Parental compliance with the regimen was good.

Topics: Antifibrinolytic Agents; Breast Feeding; Child Health Services; Denmark; Drug Administration Schedule; Drug Therapy, Combination; Food, Fortified; Health Promotion; Humans; Incidence; Infant Welfare; Infant, Newborn; Patient Compliance; Preventive Health Services; Surveys and Questionnaires; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Resistance to warfarin has been connected to an increase in dietary requirement for vitamin K in British strains of the Norway rat, Rattus norvegicus (Berk). This study examines vitamin K requirement of Danish anticoagulant-resistant Norway rats using a vitamin K deficient feeding test. Wild bromadiolone-resistant rats sampled from different localities in Denmark and rats from bromadiolone-resistant and susceptible laboratory strains were fed on a vitamin K deficient diet over a maximum period of 15 days. Development of vitamin K deficiency, measured as reduced blood-clotting capacity, took place in 43% of the Danish resistant rats and was independent of sex, treatment with supplementary vitamin K3 and sampling locality. Development of deficiency was slower for resistant rats that were supplemented with vitamin K3 prior to the feeding test, suggesting storage of the vitamin K in a vitamin body pool. Intraperitoneal administration of vitamin K1 revealed that 80 microg vitamin K1 kg(-1) bodyweight was sufficient to restore normal blood clotting activity in deficient rats, while 60 microg vitamin K1 kg(-1) bodyweight was insufficient. We conclude that vitamin K requirement is moderately increased in Danish homozygous resistant rats whereas heterozygous resistant rats only have a minor increase in vitamin K requirement compared with susceptible rats. We found no indication of different resistance types being present in our test material since vitamin K requirement was not different between rats from separate sampling localities.

Topics: 4-Hydroxycoumarins; Animals; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation; Drug Resistance; Female; Male; Rats; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Diagnosis, Differential; Humans; Infant, Newborn; Trypsin; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Humans; Imidazoles; Indicators and Reagents; Models, Molecular; Protein C; Protein C Deficiency; Protein Conformation; Prothrombin; Vitamin K; Vitamin K Deficiency

Due to maldigestion of dietary lipids, fat soluble vitamins are prone to malabsorption in cystic fibrosis (CF) patients with pancreatic insufficiency (PICF). Routine supplementation of vitamin K(1) in PICF is presently subject of discussion.. Serum vitamin K, prothrombin time, PIVKA-II ('liver marker', by two different ELISAs), hydroxyapatite binding capacity (HBC, 'bone marker') and ApoE genotypes were measured in 32 PICF patients (age: 7 months to 25 years) with (PICFK) or without (PICFN) oral vitamin K(1) supplementation, all receiving lipase supplementation, and in 18 healthy controls (C).. PIVKA-II was positive only in 4/7 PICFN. HBC medians of all groups were 57-60%. HBC values of PIVKA-II positive patients were below HBC median of their group. There was no correlation between HBC and PIVKA-II. There was no correlation between prothrombin time and other measurements. HBC medians with regard to ApoE were ApoE2/3 (62.9%)>ApoE3/3 (57.6%)>ApoE3/4+ApoE4/4=(56.65%).. Vitamin K deficiency of liver or bone may occur independently. Prothrombin time is an insensitive marker. Individuals with ApoE4 allels might be more susceptible to osteopenia. As high expenditures are necessary to detect patients at risk, routine vitamin K supplementation for all PICF patients appears appropriate.

Topics: Adolescent; Adult; Apolipoproteins E; Biomarkers; Bone Diseases, Metabolic; Case-Control Studies; Child; Child, Preschool; Cystic Fibrosis; Enzyme-Linked Immunosorbent Assay; Exocrine Pancreatic Insufficiency; Humans; Infant; Lipase; Mass Screening; Osteocalcin; Polymerase Chain Reaction; Protein Precursors; Prothrombin; Prothrombin Time; Regression Analysis; Sensitivity and Specificity; Vitamin K; Vitamin K Deficiency

We report a male infant with congenital tuberculosis who developed cerebral hemorrhage associated with vitamin K deficiency during treatment with isoniazid and rifampin. Despite an absence of risk factors for vitamin K deficiency, the severe hemorrhagic disorder occurred at 4 months of age. We speculate that vitamin K deficiency in the present case may have resulted from a synergic effect of antituberculosis agents and immaturity of vitamin K metabolism and/or its absorption.

Topics: Cerebral Hemorrhage; Humans; Infant; Infectious Disease Transmission, Vertical; Isoniazid; Male; Rifampin; Streptomycin; Tuberculosis; Vitamin K; Vitamin K Deficiency

To assess the influence of vitamin K on bone mineral density (BMD) in vitamin-D-deficient women with Parkinson's disease (PD).. Cross-sectional study.. Neurology department at a university medical center in Japan.. Sixty-two women with PD (mean age, 70.7yr) and 62 age-matched controls. Patients were divided into 2 groups according to their functional capabilities: group A (independent: stages I-II of Hoehn and Yahr stages of Parkinson's disease, n = 26); and group B (dependent: Hoehn and Yahr stages 3-5; n = 36).. Not applicable.. Sera were analyzed to relate vitamin K concentrations to bone-related biochemical indices. BMD was measured by computed radiograph densitometry.. Group B had significantly lower metacarpal BMD (P <.0001) lower serum concentrations of vitamin K1 (P <.01) and 25-hydroxyvitamin D (25-OHD; P <.0001) than group A. Serum undercarboxylated osteocalcin levels were higher in group B than in group A (P <.0001). The serum concentration of vitamin K1 correlated positively with that of 25-OHD (r =.735, P <.0001), and negatively with undercarboxylated osteocalcin (r = -.751, P <.0001) and Hoehn and Yahr stages (r =.787, P <.0001). Multiple regression analysis identified Hoehn and Yahr stages, vitamin K1, 25-OHD, and undercarboxylated osteocalcin as independent determinants of BMD (P <.0364.0003).. In functionally dependent women with PD, nutritional vitamin K1 deficiency is believed to reduce production of fully carboxylated osteocalcin, causing reduced BMD.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Bone Density; Bone Diseases, Metabolic; Chi-Square Distribution; Cross-Sectional Studies; Female; Humans; Linear Models; Middle Aged; Osteocalcin; Parkinson Disease; Vitamin D Deficiency; Vitamin K; Vitamin K Deficiency

Oxytocin has been used for several decades in close proximity to newborns, yet no published information is available regarding complications associated with its accidental administration to a newborn. We describe a case where oxytocin instead of vitamin K was accidentally administered intramuscularly to a premature infant shortly after birth. The patient described remained hemodynamically stable but developed transient hyponatremia as the sole biochemical abnormality.

Topics: Apnea; Bradycardia; Female; Humans; Hyponatremia; Infant, Newborn; Infant, Premature; Injections, Intramuscular; Medication Errors; Oxytocin; Postpartum Hemorrhage; Vitamin K; Vitamin K Deficiency

Adrenal hemorrhage has many etiologies including bleeding diathesis. A 10-day-old female baby was admitted to our clinic with the complaint of abdominal distention. Hemorrhage was determined on the right adrenal gland with abdominal ultrasonography and computerized tomography. Laboratory investigations showed PT 44 sec and aPTT longer than one minute. This article reports here an infant diagnosed as adrenal hemorrhage due to Vitamin-K deficiency presenting as an abdominal mass.

Topics: Adrenal Gland Diseases; Female; Hemorrhage; Humans; Infant, Newborn; Tomography, X-Ray Computed; Vitamin K; Vitamin K Deficiency

There is strong evidence supporting the importance of vitamin K in bone health and the aetiological role of vitamin K deficiency in osteoporosis. In view of the common occurrence of osteoporosis among older subjects in Hong Kong, we have studied the dietary vitamin K intakes in 100 residents of a nursing home (43 men, 57 women; median age 81.0 years) and 88 free-living subjects attending a day care centre (13 men, 75 women; median age 71.5 years). The subjects were interviewed and the average vitamin K intake in the preceding week was estimated, using a diet recall questionnaire modified from our previous surveys of dietary patterns in local Chinese people. The median vitamin K intake was much lower in nursing home residents than in free-living subjects (4.50 vs 488.09 microg/day or 0.13 vs 8.74 microg/kg/day, P<0.001). An intake that was below the recommended daily intake was far more common among nursing home residents (86.0 vs 11.4%, P < 0.001). Among nursing home residents, there was a negative correlation between age and vitamin K intake (r = -0.217, P = 0.030), but there was a positive correlation between body weight and vitamin K intake (r = 0.244, P = 0.015). No such relationship was seen among free-living subjects. Elderly nursing home residents in this study generally had a poor dietary vitamin K intake and might therefore be predisposed to osteoporosis. The importance of green leafy vegetables as a rich source of vitamin K should be emphasised.

Topics: Adult; Aged; Aged, 80 and over; Body Weight; Feeding Behavior; Female; Homes for the Aged; Hong Kong; Humans; Male; Middle Aged; Nursing Homes; Surveys and Questionnaires; Vitamin K; Vitamin K Deficiency

The difference between vitamin K metabolism in the liver and that in the bone of vitamin K-deficient rats was examined. After 17 d administration of vitamin K-deficient food, vitamin K in the liver was almost depleted, and prothrombin time (PT) was prolonged. Serum total osteocalcin level was slightly decreased by vitamin K deficiency, whereas serum undercarboxylated osteocalcin level did not change. The level of menaquinone (MK)-4 as well as that of phylloquinone was decreased, but approximately 40 % of the initial level still existed in the femur after the 17 d period. A single-dose administration of vitamin K (250 nmol/kg body weight) markedly increased vitamin K level in the liver but not in the femur. These results suggest that the turnover of vitamin K in the bone is slower than that in the liver, and bone metabolism may be little affected by the short period of intake of vitamin K-deficient food. However, intake of a larger amount of vitamin K is required for its accumulation in the bone than in the liver. Furthermore, the counteracting effect of MK-7 on prolonged PT in vitamin K-deficient rats was found to be higher than phylloquinone or MK-4.

Topics: Animals; Bone and Bones; Cyanoacrylates; Indoleacetic Acids; Liver; Male; Osteocalcin; Partial Thromboplastin Time; Prothrombin Time; Rats; Rats, Sprague-Dawley; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

Topics: Hemorrhage; Humans; Infant, Newborn; Injections, Intramuscular; Neoplasms; Vitamin K; Vitamin K Deficiency

Topics: Government Publications as Topic; Guideline Adherence; Humans; Infant, Newborn; Infant, Premature; Practice Guidelines as Topic; Vitamin K; Vitamin K Deficiency

Patients with cystic fibrosis (CF) and pancreatic insufficiency (PI) commonly have vitamin K deficiency, and those with CF-associated liver disease (CFLD) have universal vitamin K deficiency. We evaluated the effectiveness of an oral fat-soluble vitamin combination (ADEKs) to treat patients with vitamin K deficiency.. Patients with PI and CF (mean age, 15 years; range, 0.6 to 46 years) including 6 with advanced CFLD were prospectively enrolled in a study of a fat-soluble vitamin combination taken on a daily basis. None had received vitamin K supplementation for at least 4 months before the study. Fat-soluble vitamin combination supplementation was given for a minimum of 4 months; the mean vitamin K intake was 0.18 mg/d (SD = 0.1, range, 0 to 0.3). The primary outcome was change in plasma PIVKA-II (prothrombin in vitamin K absence).. Before supplementation 58 (81%) of 72 patients had abnormal PIVKA-II levels (>2.9 ng/mL). After supplementation 29 (40%) had abnormal PIVKA-II levels (P =.001). All 6 patients with advanced CFLD had abnormal PIVKA-II levels (median, range of 20.8, 5.5 to 55 ng/mL) before treatment, which corrected to normal in 50% (4.1, 2.1 to 65 ng/mL). Four patients, 2 with CFLD, had a prolonged prothrombin time (>13.5 seconds) at both time periods.. An oral fat-soluble vitamin combination with a modest amount of vitamin K can, as a daily supplement, improve the PIVKA-II levels in patients with PI and CF.

Topics: Adolescent; Adult; Biomarkers; Child; Child, Preschool; Cystic Fibrosis; Female; Humans; Infant; Liver Diseases; Male; Middle Aged; Prospective Studies; Protein Precursors; Prothrombin; Prothrombin Time; Vitamin K; Vitamin K Deficiency; Vitamins

Calciphylaxis is a rare disorder of small-vessel calcification and cutaneous infarction associated with chronic renal failure. Rare cases of calciphylaxis not associated with chronic renal failure have been reported with breast cancer, hyperparathyroidism, and alcoholic cirrhosis. To our knowledge, we report the first case of calciphylaxis without chronic renal failure associated with cholangiocarcinoma and the first attempt to treat calciphylaxis with vitamin K. A 56-year-old woman presented with necrotic leg ulceration. She was treated initially with low-molecular-weight heparin, with no effect. A coagulation work-up showed vitamin K deficiency. During vitamin K therapy, the patient had fulminant progression of the calciphylaxis. She died, and an autopsy showed metastatic cholangiocarcinoma. Thrombosis and protein C deficiency have been implicated in the pathophysiology of calciphylaxis. Functional protein C deficiency may be one of several factors contributing to the development of calciphylaxis. Vitamin K therapy was ineffective in our patient and may have been detrimental.

Topics: Adenocarcinoma; Anticoagulants; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biopsy; Calciphylaxis; Cholangiocarcinoma; Fatal Outcome; Female; Heparin, Low-Molecular-Weight; Humans; Leg Ulcer; Liver Neoplasms; Lung Neoplasms; Middle Aged; Necrosis; Neoplasms, Multiple Primary; Prognosis; Sepsis; Vitamin K; Vitamin K Deficiency

Topics: Blood Coagulation; Carbon-Carbon Ligases; Hemorrhagic Disorders; Humans; Infant, Newborn; NAD(P)H Dehydrogenase (Quinone); Terminology as Topic; Vitamin K; Vitamin K Deficiency

Neonates on exclusive breast feeding that do not receive vitamin K at birth are at higher risk hemorrhagic disease of the newborn.. To compare the effect of oral or intramuscular administration of vitamin K1 (VK1), on clotting factors II, VII, IX, X and PIVKA II, in children until the 60 days of age with exclusive breast feeding or mixed feeding.. Forty healthy full term infants, distributed in two groups, A: 20 with mixed feeding (formula-feeding and breast-feeding) and B: 20 with exclusive breast feeding, were studied. Nine infants of each group received 1 mg of VK1 intramuscularly and eleven 2 mg VK orally 5 ml of cord blood was collected initially from each infant. Venous blood samples were taken on 15, 30 and 60 days of age.. All factors increased in a progressive form reaching levels over 50% at 60 days of age, in both groups. PIVKA II decreased significantly during the study period (p < 0.01). Factor II increased more in children with mixed feeding that received intramuscular vitamin K, than in the rest of study groups. No other differences between groups were observed. No infant had an abnormal bleeding during the study period.. Oral administration of vitamin K is as effective as the intramuscular route in the prevention of the hemorrhagic disease of the newborn.

Topics: Administration, Oral; Biomarkers; Blood Coagulation Factors; Breast Feeding; Factor IX; Factor VII; Factor X; Female; Humans; Infant; Infant, Newborn; Injections, Intramuscular; Male; Protein Precursors; Prothrombin; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Late hemorrhagic disease of the newborn (HDN) may occur without an underlying disorder or as a secondary manifestation of an underlying disorder. It may be seen in fully breast-fed infants without a routine supplementation of vitamin K. In contrast, idiopathic late HDN is defined as HDN without the presence of any risk factor, such as gastroenteritis or use of antibiotics. Severe hemorrhagic symptoms frequently occur.. Between March 1987 and May 1997, we evaluated 15 infants with idiopathic late HDN, who were diagnosed by detailed history, physical examination and laboratory findings.. The age (mean +/- SD) at onset of symptoms was 62.4 +/- 33.9 days. All children were breast-fed infants and were born at term from healthy mothers. The delivery histories were uneventful. There was no history of vitamin K administration at birth. Signs and symptoms of the patients were convulsions (47%), feeding intolerance and poor sucking (47%), irritability (33%) and pallor (20%). In physical examination; there was bulging or full fontanel in 10 patients (67%), diminished or absent neonatal reflexes in nine patients (60%) and ecchymosis in three patients (20%). Before administration of vitamin K, prothrombin time (PT) was 76.1 +/- 43.0 s and partial thromboplastin time (PTT) was 123.4 +/- 68.8 s. Six to 12 h after administration of vitamin K, PT was 15.6 +/- 1.8 s and PTT was 33.4 +/- 1.0 s. Neurologic, gastrointestinal and skin hemorrhagic findings were found in 11 (73%), three (20%) and three patients (20%), respectively. There were both neurologic and skin bleeding symptoms in two patients. The mortality in the present study was 33%.. Late HDN results in severe hemorrhage, especially hemorrhage in the central nervous system. Administration of vitamin K (1 mg, i.m.) at the birth can reduce these severe complications.

Topics: Age of Onset; Breast Feeding; Humans; Infant; Infant, Newborn; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

The aim of the present study was to assess how high doses of dietary vitamin K influence the intestinal profile of K-vitamins in vitamin K-deficient rats, and whether the induced changes are reflected in the hepatic vitamin K store. Vitamin K-deficient rats were fed for 10 d on diets containing different forms of vitamin K, and it was determined how these diets affected the vitamin K concentration at various sites of the instestine, serum, and the liver. It was found that the absorption of phylloquinone from standard food is not more than 10%, while the absorption of pharmacological doses of oil-solubilized phylloquinone and menaquinone-4 was also far from complete (18 and 55% respectively). High intakes of phylloquinone suppress the colonic production of all higher menaquinones. High menaquinone-4 intake induces very high menaquinone-8 concentrations, both in the colonic contents as well as in the liver. These data suggest that menaquinone-4 may be converted into menaquinone-8 (but not into other menaquinones) via a metabolic pathway which has not been reported previously.

Topics: Absorption; Animals; Gastrointestinal Contents; Intestinal Mucosa; Liver; Male; Rats; Rats, Inbred Lew; Vitamin K; Vitamin K Deficiency

Topics: Aged; Apolipoprotein E4; Apolipoproteins E; Bone Density; Cohort Studies; Female; Hip Fractures; Humans; Male; Osteoporosis; Vitamin K; Vitamin K Deficiency

Vitamin K has been associated with bone mineral density (BMD) and risk of hip fracture. The apolipoprotein (apo) E4 allele (APOE*E4) has been associated with bone fracture through a putative effect on vitamin K transport in blood.. The objective was to determine the associations between vitamin K intake, apo E genotype, BMD, and hip fracture in a population-based cohort of elderly men and women.. Dietary vitamin K intake was assessed with a food-frequency questionnaire in 335 men and 553 women (average age: 75.2 y) participating in the Framingham Heart Study in 1988-1989. Incidence of hip fractures was recorded from 1988 to 1995. BMD at the hip, spine, and arm was assessed on 2 separate occasions (1988-1989 and 1992-1993). Comparisons between apo E genotype and BMD were made relative to E4 allele status (at least 1 epsilon4 allele compared with no epsilon4 allele).. Individuals in the highest quartile of vitamin K intake (median: 254 microg/d) had a significantly lower fully adjusted relative risk (0.35; 95% CI: 0. 13, 0.94) of hip fracture than did those in the lowest quartile of intake (median: 56 microg/d). There were no associations between vitamin K intake and BMD in either men or women. No association was found between the E4 allele and BMD, and there were no significant interactions between the E4 allele and phylloquinone intake and BMD or hip fracture.. Low vitamin K intakes were associated with an increased incidence of hip fractures in this cohort of elderly men and women. Neither low vitamin K intake nor E4 allele status was associated with low BMD.

Topics: Absorptiometry, Photon; Aged; Aged, 80 and over; Apolipoprotein E4; Apolipoproteins E; Body Mass Index; Bone Density; Cohort Studies; Dietary Supplements; DNA; Eating; Electrophoresis, Polyacrylamide Gel; Estrogen Replacement Therapy; Female; Follow-Up Studies; Hip Fractures; Humans; Linear Models; Male; Polymerase Chain Reaction; Surveys and Questionnaires; Vitamin K; Vitamin K Deficiency

To further characterize the skeletal role of vitamin K (K), markers of bone turnover, density, and strength were evaluated in rats with diet- or warfarin (W)-induced K insufficiency. One hundred two, 7-week-old, female rats were randomly assigned to low K (phylloquinone [K1], 20 microg/kg diet), control K (K1, 1300 microg/kg diet), low-dose W (W, 1.5 mg/kg control diet), or high-dose W plus K (W/K1, 10/100 mg/kg diet). Femur bone mineral content (BMC) and bone mineral density (BMD), plasma prothrombin time (PT) and prothrombin concentration (PC), and serum total alkaline phosphatase (ALP) and skeletal alkaline phosphatase (sALP) were measured at baseline and days 20, 40, 60, and 80. Serum total osteocalcin (OC) and undercarboxylated osteocalcin (ucOC) and femur length (FL) were measured at baseline and day 80. Left femur OC was measured and biomechanical testing of the right femur and third lumbar vertebral body was performed at day 80. Low dietary K elevated circulating ucOC (17% higher than control; p < 0.0001) at day 80. Furthermore, in both W groups, essentially all circulating OC was undercarboxylated and femur OC was lower than control (p < 0.0001). However, there was no change in femur percent ucOC, suggesting deposition of less newly synthesized OC. No between group differences were observed in PT, ALP, sALP, FL, BMC, BMD, or bone strength. In conclusion, skeletal K insufficiency can be induced by W or diet manipulation. This does not hinder peak bone mass attainment in female rats; however, W causes less newly synthesized OC to be deposited in bone.

Topics: Absorptiometry, Photon; Animals; Anticoagulants; Bone and Bones; Bone Density; Bone Development; Carboxylic Acids; Diet; Female; Osteocalcin; Rats; Vitamin K; Vitamin K Deficiency; Warfarin

Vitamin K is a trace nutrient necessary not only for the synthesis of four plasma clotting factors but also the production of two important anticlotting factors, protein C and protein S, and the synthesis of two bone proteins. If protein C and protein S are produced more quickly and/or in higher quantities than four plasma coagulation factors after vitamin K administration, then the result is unfavorable for stopping of hemorrhage. We therefore studied the difference of time dependence of prothrombin procoagulant factors, protein C and S and bone Gla protein after the administration of vitamin K in normal and vitamin K-deficient neonates. Results of our study showed that, on the whole, coagulation factors increased markedly more than anticlotting factors after vitamin K administration. Furthermore, the increase in bone Gla protein was also higher compared with protein C activity, although the detailed mechanism of the difference in reactivity of prothrombin procoagulant factors, protein C and S and bone Gla protein to vitamin K administration is not clear.

Topics: Female; Gene Expression Regulation; Gestational Age; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Osteocalcin; Protein C; Protein S; Vitamin K; Vitamin K Deficiency

Topics: Breast Feeding; Female; Follow-Up Studies; Humans; Infant; Injections, Intramuscular; Intracranial Hemorrhages; Magnetic Resonance Imaging; Tomography, X-Ray Computed; Vitamin K; Vitamin K Deficiency

Topics: Follow-Up Studies; Hematuria; Hemorrhage; Humans; Infant, Newborn; Male; Treatment Outcome; Urinary Bladder Diseases; Vitamin K; Vitamin K Deficiency; Vomiting

A 87-year-old patient developed coagulation abnormality following hip surgery related to the prophylactic use of cefamandole. Cefamandole as others cephalosporins with a methyl-tetrazol-thiol lateral chain interferes with the vitamin K regeneration cycle as do oral anticoagulants. Therefore, the use of others antibiotics or systematic vitamin K1 supplementation or single dose of cefamandole is recommended for patients with renal failure or with malnutrition. Vitamin K1 supplementation is a simple method resulting in complete resolution of the coagulation disorder.

Topics: Aged; Aged, 80 and over; Antibiotic Prophylaxis; Arthroplasty, Replacement, Hip; Cefamandole; Cephalosporins; Female; Femoral Neck Fractures; Hematoma; Hemorrhagic Disorders; Humans; Postoperative Complications; Vitamin K; Vitamin K Deficiency

A mutation in the gamma-glutamyl carboxylase gene leading to a combined congenital deficiency of all vitamin K-dependent coagulation factors was identified in a Lebanese boy. He is the first offspring of consanguineous parents and was homozygous for a unique point mutation in exon 11, resulting in the conversion of a tryptophan codon (TGG) to a serine codon (TCG) at amino acid residue 501. Oral vitamin K(1) administration resulted in resolution of the clinical symptoms. Screening of several family members on this mutation with an RFLP technique revealed 10 asymptomatic members who were heterozygous for the mutation, confirming the autosomal recessive pattern of inheritance of this disease. In 50 nonrelated normal subjects, the mutation was not found. This is the second time a missense mutation in the gamma-glutamyl carboxylase gene is described that has serious impact on normal hemostasis.

Topics: Blood Coagulation Factors; Carbon-Carbon Ligases; DNA Mutational Analysis; Hemorrhage; Homozygote; Humans; Male; Molecular Sequence Data; Mutation; Mutation, Missense; Osteocalcin; Pedigree; Point Mutation; Vitamin K; Vitamin K Deficiency

Topics: Anticoagulants; Hemoptysis; Humans; Male; Middle Aged; Phenprocoumon; Pulmonary Alveoli; Vitamin K; Vitamin K Deficiency

Hereditary combined deficiency of the vitamin K dependent coagulation factors is a rare bleeding disorder. To date, only eleven families have been reported in the literature. The phenotype varies considerably with respect to bleeding tendency, response to vitamin K substitution and the presence of skeletal abnormalities, suggesting genetic heterogeneity. In only two of the reported families the cause of the disease has been elucidated as either a defect in the gamma-carboxylase enzyme (1) or in a protein of the vitamin K 2,3-epoxide reductase (VKOR) complex (2). Here we present a detailed phenotypic description of two new families with an autosomal recessive deficiency of all vitamin K dependent coagulation factors. In both families offspring had experienced severe or even fatal perinatal intracerebral haemorrhage. The affected children exhibit a mild deficiency of the vitamin K dependent coagulation factors that could be completely corrected by oral substitution of vitamin K. Sequencing and haplotype analysis excluded a defect within the gamma-carboxylase gene. The finding of highly increased amounts of vitamin K epoxide in all affected members of both families indicated a defect in a protein of the VKOR-multienzyme-complex. Further genetic analysis of such families will provide the basis for a more detailed understanding of the structure-function relation of the enzymes involved in vitamin K metabolism.

Topics: Blood Coagulation Factors; Carbon-Carbon Ligases; Family Health; Female; Genes, Recessive; Hemorrhage; Humans; Infant; Infant, Newborn; Male; Mixed Function Oxygenases; Pedigree; Phenotype; Sequence Analysis; Vitamin K; Vitamin K Deficiency; Vitamin K Epoxide Reductases

Topics: Female; Home Childbirth; Hospitalization; Humans; Infant, Newborn; Midwifery; Milk, Human; Pregnancy; Texas; Vitamin K; Vitamin K Deficiency; Water

Topics: Cerebral Hemorrhage; Continuity of Patient Care; Evidence-Based Medicine; Female; Health Knowledge, Attitudes, Practice; Humans; Infant Food; Infant, Newborn; Midwifery; Milk, Human; Pregnancy; Reference Values; Unnecessary Procedures; Vitamin K; Vitamin K Deficiency

Topics: Administration, Oral; Female; Humans; Infant Food; Infant Nutritional Physiological Phenomena; Infant, Newborn; Injections, Intramuscular; Midwifery; Milk, Human; Pregnancy; Unnecessary Procedures; Vitamin K; Vitamin K Deficiency

Gender differences in relation to vitamin K were investigated in the rat. Hepatic phylloquinone and menaquinone (MK-1 to MK-10) concentrations, gamma-carboxyglutamic acid (Gla) excretion, plasma phylloquinone and percent prothrombin were measured in male and female rats on a chow diet (24.5 ng phylloquinone and 8.8 microgram menadione), and on phylloquinone-deficient and -supplemented purified diets (0.38 and 1400 ng phylloquinone/g, respectively). Mean hepatic phylloquinone concentrations varied with dietary intake and ranged from 6.8+/-9.0 pmol/g in the deficient male, to 171. 1+/-56.9 pmol/g in the supplemented female. Menaquinones accounted for a large proportion of total vitamin K in the liver of males and females with MK-4, MK-6, and MK-10 present in highest concentrations. On the chow and supplemented diets, females had significantly higher MK-4, MK-6, and MK-10 concentrations in their livers (P<0.05). On the phylloquinone-deficient diet (-K1), hepatic phylloquinone, MK-4, and to a lesser extent MK-6 (but not MK-10) were significantly reduced (P<0.05). In the phylloquinone-supplemented male and female groups, which did not receive menadione during the experimental period, MK-4 increased above that in the chow groups suggesting synthesis of MK-4 from phylloquinone which was statistically significant in the female (P<0.01). A significant gender difference (P<0.05) was also observed for urinary Gla excretion with less Gla excreted by the females indicating that females may require less dietary phylloquinone than males of the same body weight.

Topics: 1-Carboxyglutamic Acid; Animals; Chromatography, High Pressure Liquid; Diet; Humans; Liver; Male; Prothrombin; Rats; Rats, Sprague-Dawley; Sex Factors; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

To investigate the effects of vitamin K (VK) on pancreatic function, intravenous glucose tolerance tests were performed in rats fed with and without low VK diet (including less than 20% required vitamin K1). Plasma glucose and immuno-reactive insulin (IRI) were determined. It was found that at 0 min., plasma glucose and IRI levels in low VK group were slightly less than in the control (glucose, 204.5 +/- 21.7 vs. 229 +/- 19.6 mg/dl, IRI, 6.6 +/- 1.3 vs. 9.3 +/- 1.8 ng/ml mean +/- SEM). At 3 min. after glucose administration, plasma glucose was higher (391.8 +/- 25.6 vs. 371.8 +/- 18.7 mg/dl) and IRI, lower (11.8 +/- 2.1 vs. 18.2 +/- 3.6 ng/ml) in the low VK group. The disappearance rate of plasma glucose in the low VK group at 5-10 min. was significantly less than in the control (6.7 +/- 2.2 vs. 11.9 +/- 1.8 mg/dl/min.). Incremental IRI area at 0 to 5 min. in the low VK group is less than in the control (15.2 +/- 4.4 vs. 25.0 +/- 9.1 ng/ml/min.), but at 5-60 min. and 0-60 min., it was found to be significantly higher compared to the control (210.3 +/- 55.2 vs. 32.5 +/- 47.1 ng/ml/min. at 5-60 min.). Dietary low VK intake would thus appear to induce a tendency of poor early insulin response, and late hyperinsulinemia to the glucose load in rats.

Topics: Animals; Blood Glucose; Glucose; Glucose Tolerance Test; Injections, Intravenous; Insulin; Kinetics; Liver; Male; Pancreas; Rats; Rats, Sprague-Dawley; Vitamin K; Vitamin K Deficiency

Vitamin K deficiency is a common occurrence in the surgical and intensive care unit population, but its incidence in kidney and combined kidney-pancreas allograft recipients has not been described. We report four patients who received cadaveric kidney or combined kidney-pancreas allografts and subsequently developed significant bleeding associated with deficiency of vitamin K. Their coagulopathy promptly resolved with the parenteral administration of vitamin K. Treatment with vitamin K should be considered in kidney or combined kidney-pancreas allograft recipients with a prolonged prothrombin or partial thromboplastin time during the first postoperative week to avoid hemorrhagic complications.

Topics: Adult; Aged; Blood Coagulation Tests; Female; Hemorrhage; Humans; Kidney Transplantation; Male; Middle Aged; Pancreas Transplantation; Postoperative Complications; Vitamin K; Vitamin K Deficiency

To determine whether anticonvulsant exposure during human pregnancy caused an increase of the abnormal form of prothrombin, known as PIVKA-II (prothrombin induced by vitamin K absence for factor II), and a decrease in total prothrombin, in the blood of the newborn.. Cord blood was collected from the placenta at the time of parturition from 12 women who had received anticonvulsant therapy during pregnancy and from 11 control women.. PIVKA-II was present in cord blood from control mothers at low or nondetectable levels. In the same samples, total prothrombin concentrations were approximately 50% of adult levels, but there was wide variation between individuals. Exposure to carbamazepine (CBZ) alone during pregnancy was associated with markedly increased PIVKA-II levels in four of six samples and decreased total prothrombin levels for the whole group. High PIVKA-II levels also were recorded in one cord blood sample from a mother who received phenytoin (PHT) and vigabatrin (VGB). Two cases of PHT alone and one of valproic acid (VPA) alone were not associated with increased PIVKA-II levels.. These results are consistent with the hypothesis that some anticonvulsants (particularly CBZ) interfere with vitamin K metabolism during pregnancy and may result in hematologic signs of vitamin K deficiency in the newborn.

Topics: Adult; Anticonvulsants; Biomarkers; Biomarkers, Tumor; Epilepsy; Female; Fetal Blood; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications; Protein Precursors; Prothrombin; Vitamin K; Vitamin K Deficiency

Topics: Humans; Infant, Newborn; Vitamin K; Vitamin K Deficiency

A 3-month-old male infant with intracranial hemorrhage attributable to a vitamin K deficiency is reported. Vitamin K2 was administered orally at birth and then at 5 days and I month of age. Oral antibiotics were also given 2 days before the onset of bleeding. Although the incidence of intracranial hemorrhage resulting from vitamin K deficiency has decreased since the introduction of vitamin K2 prophylaxis, spontaneous intracranial hemorrhages are still being reported in infants. We suggest that vitamin K prophylaxis is needed especially for breast-fed infants and for those undergoing antibiotic therapy.

Topics: Cerebral Hemorrhage; Drug Administration Schedule; Humans; Infant; Male; Risk Factors; Vitamin K; Vitamin K Deficiency

Topics: Dietary Supplements; Hemorrhage; Humans; Infant, Newborn; Vitamin K; Vitamin K Deficiency

Topics: Adult; Bile Ducts, Intrahepatic; Cerebral Hemorrhage; Fatal Outcome; Female; Humans; Infant; Male; Vitamin K; Vitamin K Deficiency

Topics: Adolescent; Adult; Aged; Apolipoprotein A-I; Apolipoproteins B; Fractures, Bone; Humans; Male; Mathematics; Middle Aged; Osteocalcin; Vitamin K; Vitamin K Deficiency

A 1 mg dose of vitamin K given intramuscularly at birth prevents almost all cases of late VKDB, whereas even two oral doses of 1 mg vitamin K given in the first week and a third given in week 5 to 6 are less effective. Is efficacy improved by increasing the dose to 3 x 2 mg? For active surveillance of VKDB, monthly postcards which include a nothing-to-report option, were sent to all heads of pediatric hospitals in Germany from January 1995 to December 1998. All reports were validated according to a standard case definition for late VKDB by means of a questionnaire. The incidence of VKDB with three oral doses of 2 mg vitamin K is compared to previously published rates for VKDB on 3 oral 1 mg oral doses, which had been ascertained with the same surveillance scheme. The number of cases of VKDB (excluding the failure-of-management cases) in children aged 8 days to 12 completed weeks during the 4 year period was 23. 14 had intracranial hemorrhage, 22 had been exclusively breastfed, and in 20 cholestasis was detected after the bleeding episode. 14/23 had been given all recommended 2 mg doses for vitamin K prophylaxis. Until 1996 all had been given the cremophor vitamin K preparation, whereas in 1997 to 1998 two children with late VKBD had received the new mixed micellar (MM) preparation, first licensed in July 1996. The incidence of VKBD per 100,000 live births during the 1995 to 1998 period was 0.72, including children given no vitamin K prophylaxis, and 0.44 for children who had received all age-related recommended vitamin K doses. These incidence rates are significantly lower than those previously published for the 3 x 1 mg dose regimen in Germany (1.8 cases of late VKDB per 100,000 live births in children who had received all recommended vitamin K doses). Not all cases of late VKDB, however, are prevented by the 3 x 2 mg dose regimen, even if the new mixed micellar preparation is given instead of the cremophor preparation.

Topics: Administration, Oral; Denmark; Germany; Humans; Incidence; Infant; Infant, Newborn; Netherlands; Treatment Outcome; Vitamin K; Vitamin K Deficiency

Two forms of vitamin K [phylloquinone (K1) and menaquinone-4 (MK-4)] were added to vitamin K-deficient rat food in varying amounts. These diets were given as the sole source of nutrition to rats for one week. The minimal dietary requirements (MDR) to attain maximal prothrombin synthesis were determined to be 0.6 and 6-10 microg/g of food for K1 and MK-4, respectively. The difference between both vitamers could be explained by the limited hepatic accumulation of MK-4. Next, vitamin K was offered to rats at concentrations ranging between 0.6 and 3000 microg/g of food, and the tissue distribution of vitamin K was investigated after one week of administration. Accumulation of K1 and MK-4 was found in all tissues investigated, but both the absolute tissue concentration and the ratio between K1 and MK-4 were tissue-dependent. Highest values were found in liver and in heart, but since the heart contains no gamma-glutamylcarboxylase, the function of vitamin K in this tissue remains obscure. High tissue concentrations of MK-4 were also found in pancreas and testis after a diet containing K1 exclusively. The data indicate that this conversion is tissue-specific, but neither the reason nor its mechanism are known.

Topics: Animal Nutritional Physiological Phenomena; Animals; Carbon-Carbon Ligases; Diet; Dietary Supplements; Liver; Male; Myocardium; Prothrombin; Rats; Rats, Inbred Strains; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

To elucidate the role of intestinal bacteria in the conversion of phylloquinone into menaquinone-4 (MK-4) we investigated the tissue distribution of vitamin K in germ-free rats. The rats were made vitamin K deficient by feeding a vitamin K-free diet for 13 days. In a subsequent period of 6 days, phylloquinone and menadione were supplied via the drinking water in concentrations of 10 and 50 micromol l(-1). Menadione supplementation led to high levels of tissue MK-4, particularly in extrahepatic tissues like pancreas, aorta, fat and brain. Liver and serum were low in MK-4. Phylloquinone supplementation resulted in higher phylloquinone levels in all tissues when compared with vitamin K-deficient values. The main target organs were liver, heart and fat. Remarkably, tissue MK-4 levels were also higher after the phylloquinone supplementation. The MK-4 tissue distribution pattern after phylloquinone intake was comparable with that found after menadione intake. Our results demonstrate that the conversion of phylloquinone into MK-4 in extrahepatic tissues may occur in the absence of an intestinal bacterial population and is tissue specific. A specific function for extrahepatic MK-4 or a reason for this biochemical conversion of phylloquinone into MK-4 remains unclear thus far.

Topics: Animals; Diet; Germ-Free Life; Intestines; Male; Rats; Rats, Wistar; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

To test the hypothesis of an association between neonatal intramuscular vitamin K and childhood leukaemia and other cancers.. Population based case-control study with data abstracted from hospital records.. Scotland.. Children aged 0-14 years resident in Scotland from 1991-4 and diagnosed with leukaemia (150), lymphomas (46), central nervous system tumours (79), a range of other solid tumours (142), and a subset of acute lymphoblastic leukaemia (129). Controls were 777 children matched for age and sex, providing 417 matched sets (360 triplets and 57 pairs) for analysis.. Odds ratios for the risk of childhood leukaemia and cancer and intramuscular vitamin K versus a combined group of oral doses, none, and no record. Results are given for information recorded in medical notes and data supplemented by hospital policy.. Odds ratios based on medical record abstractions showed no significant positive association for leukaemias (odds ratio 1.30; 95% confidence interval 0.83 to 2.03), acute lymphoblastic leukaemia (1.21; 0.74 to 1.97), lymphomas (1.06; 0.46 to 2.42), central nervous system tumours (0.74; 0.40 to 1.34), and other solid tumours (0.59; 0.37 to 0.96). There was no association with acute lymphoblastic leukaemia in children aged 1 to 6 years. Imputation of exposure from hospital policy gave similar results. Adjustment for deprivation and type of delivery moved risk estimates closer to unity for all major diagnostic groups.. The observation of an increased risk of childhood leukaemia and cancer associated with intramuscular vitamin K is not confirmed by this independent population based study.

Topics: Adolescent; Case-Control Studies; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Injections, Intramuscular; Leukemia; Neoplasms; Odds Ratio; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Scotland; Vitamin K; Vitamin K Deficiency

To investigate the possible link between neonatal administration of intramuscular vitamin K and childhood cancer.. Matched case-control study.. Selected large maternity units in England and Wales.. Children with cancer born 1968-85, diagnosed 1969-86; controls matched for sex, month of birth, and hospital of birth.. Neonatal administration of vitamin K, length of gestation, birth weight, type of delivery, admission to special care baby unit.. After exclusion of cases with missing notes or unknown hospital vitamin K policy, 597 cases and matched controls were studied. Written records on the use of vitamin K were available for only about 40% of these, and to avoid possible bias from selective recording it was assumed that the stated hospital policy was followed. The association between cancer generally and intramuscular vitamin K was of borderline significance (odds ratio 1.44, P = 0.05); the association was strongest for leukaemia. There was, however, also an effect of abnormal delivery, which could explain some of the findings.. The lack of consistency between the various studies so far published, including this one, and the low relative risks found in most of them suggest that the risk, if any, attributable to the use of vitamin K cannot be large, but the possibility that there is some risk cannot be excluded. A comparison of the predicted consequences of various policies shows that even a 10% increase would imply that prophylaxis using the commonly recommended 1 mg intramuscular dose should be restricted to babies at particularly high risk of vitamin K deficiency bleeding; alternatively a lower dose might be given to a larger proportion of those at risk.

Topics: Adolescent; Case-Control Studies; Child; Child, Preschool; England; Humans; Infant; Infant, Newborn; Injections, Intramuscular; Neoplasms; Odds Ratio; Risk Factors; Vitamin K; Vitamin K Deficiency; Wales

To investigate the possible link between neonatal administration of intramuscular vitamin K and childhood cancer.. Ecological studies comparing incidence of cancer in groups of children classified by the vitamin K policy in operation at their hospital of birth.. Selected large maternity units in England, Scotland, and Wales.. Children born in these units in varying periods between 1966 and 1991.. Cancer occurring among these children before age 15 years identified by using the National Registry of Childhood Tumours. Ratios of observed to expected numbers of these conditions calculated for hospitals where the policy was to give all babies intramuscular vitamin K (non-selective) and where the policy was to use this treatment only for a selected minority of babies at increased risk of vitamin K deficiency bleeding (selective).. These ratios were calculated for children born in 94 hospitals with varying vitamin K policies. A raised risk was occasionally associated with vitamin K, but the overall results were not significant, and there was no evidence to support the previously suggested doubling of the risk of childhood cancer.. On the basis of the results reported here it is unlikely that there is a greatly increased risk of childhood cancer attributable to intramuscular vitamin K given to newborns, if indeed there is any.

Topics: Adolescent; Child; Child, Preschool; England; Follow-Up Studies; Humans; Incidence; Infant; Infant, Newborn; Injections, Intramuscular; Neoplasms; Nurseries, Hospital; Organizational Policy; Risk Factors; Scotland; Surveys and Questionnaires; Vitamin K; Vitamin K Deficiency; Wales

To explore the possible association between intramuscular vitamin K given to neonates and the subsequent development of childhood cancer.. Retrospective case-control study on the basis of hospital records.. The former Northern Health region of England.. 685 children who were born and lived in the region and who developed cancer before their 15th birthday, and 3442 controls also born between 1960 and 1991 and matched only for date and hospital of birth. The notes of a further 701 index cases were untraceable.. Administration of intramuscular vitamin K versus no exposure to vitamin K.. There was no association between the administration of vitamin K and the development of all childhood cancers (unadjusted odds ratio 0.89; 95% confidence interval 0.69 to 1.15) or for all acute lymphoblastic leukaemia (1.20; 0.75 to 1.92), but there was a raised odds ratio for acute lymphoblastic leukaemia developing 1-6 years after birth (1.79; 1.02 to 3.15). No such association was seen in a separate cohort-based study not dependent on case note retrieval in which the rates of acute lymphoblastic leukaemia in children born in hospital units where all babies received vitamin K were compared with those born in units where less than a third received prophylaxis.. It is not possible, on the basis of currently published evidence, to refute the suggestion that neonatal intramuscular vitamin K administration increases the risk of early childhood leukaemia. Any association may have been masked in earlier studies that did not use controls matched for time and locality by other unidentified factors affecting the spatiotemporal variations in incidence of leukaemia.

Topics: Adolescent; Case-Control Studies; Child; Child, Preschool; Cohort Studies; England; Humans; Incidence; Infant; Infant, Newborn; Neoplasms; Nurseries, Hospital; Odds Ratio; Organizational Policy; Retrospective Studies; Vitamin K; Vitamin K Deficiency

Vitamin K is a group name for a number of prenylated 2-methyl-1,4-naphtoquinones, which may differ in their ability to function as a cofactor for prothrombin biosynthesis. To quantify the bioactivity of different forms of vitamin K, two experimental animal systems are frequently used: vitamin K-deficient rats and anticoagulated rats. In this paper both models are compared, and it is shown that the results obtained depend on the model used. The main reason for this discrepancy is the difference in recycling of vitamin K-epoxide, which results in a 500 times higher vitamin K requirement in anticoagulated rats. Absorption and hepatic accumulation of long chain menaquinones seem to be restricted to a maximum, whereas also the lipophilic nature of long chain menaquinones may hamper the quinone-quinol reduction in anticoagulated animals. If these data may be extrapolated to patients, food items rich in K1 and MK-4 would be expected to influence the stability of oral anticoagulation to a much larger extent than food items primarily containing higher menaquinones.

Topics: 4-Hydroxycoumarins; Absorption; Animals; Anticoagulants; Blood Coagulation; Disease Models, Animal; Male; Prothrombin; Rats; Rats, Inbred Lew; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

Hyperemesis gravidarum is a condition of pregnancy characterized by excessive nausea and vomiting, which can be associated with malnutrition. Vitamin K deficiency is a known complication of malnutrition as well as a known cause of coagulopathy. To date, there is no reported case in the literature of vitamin K deficiency in hyperemesis gravidarum.. A woman at 15 weeks' gestation presented with hyperemesis gravidarum complicated by an episode of severe epistaxis. Investigation revealed coagulopathy secondary to vitamin K deficiency. The coagulopathy resolved after vitamin K replacement, with complete correction of all clotting factors.. Vitamin K deficiency and coagulopathy should be considered in women with hyperemesis gravidarum who present with a bleeding diathesis. Prophylactic vitamin K replacement should be considered in cases in which hyperemesis is severe and protracted.

Topics: Adult; Blood Coagulation Disorders; Female; Humans; Hyperemesis Gravidarum; Pregnancy; Vitamin K; Vitamin K Deficiency

Topics: Administration, Oral; Drug Administration Schedule; Hemorrhage; Humans; Infant Food; Infant, Newborn; Injections, Intramuscular; Leukemia; Neoplasms; Risk Factors; Vitamin K; Vitamin K Deficiency

Topics: Child; Child, Preschool; Humans; Infant; Infant, Newborn; Neoplasms; Risk Factors; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

To explore the effect of various levels of vitamin K intake on bone development.. Forty weanling Wistar male rats were divided into four groups. In one group, 1% sulfadiazine was added to regular diet (vitamin K 50 micrograms/kg) to induce vitamin K deficiency. In the other three groups, the vitamin K levels in diets were 50 micrograms/kg, 300 micrograms/kg, 2,550 micrograms/kg respectively. Twelve weeks later, the rats were killed and the effects of the different levels of vitamin K intake on bone development were evaluated by the parameters of calcium metabolism, bone metabolic biochemistry, and bone mineral density (BMD).. Vitamin K did not affect the intestinal absorption of calcium. Vitamin K deficiency led to the high levels of urinary calcium and hydroxyapatite excretion, suggesting an increase of bone absorption. Different levels of dietary vitamin K significantly affect circulating osteocalcin and OCbound content. The level of serum2 osteocalcin, OCbound and BMD elevated with the increase of dietary VK levels, whereas the parameters of PTH (thrombo plastin time) were not different between all groups.. Vitamin K can enhance the bone development of rat. The rat vitamin K requirement may be higher than that of the current recommendation (50 micrograms/kg).

Topics: Animals; Bone and Bones; Bone Density; Bone Development; Male; Rats; Rats, Wistar; Vitamin K; Vitamin K Deficiency

Vitamin K deficiency bleeding cases in Thailand from 1963 to 1995 were extensively studied. From 1963 to 1987 there were 499 reported cases from 10 papers including 102 cases of the authors' series. From March 1994 to April 1996, two subsequent nationwide surveys were conducted where questionnaires were sent to 714 and 732 hospitals located throughout Thailand. The responding rate was 58.2% and 67% respectively. 331 cases were found during 1988 to 1995. The total number was 830 cases of which 799 were idiopathic vitamin K deficiency in infancy (IVKDI) and 31 were secondary types. IVKDI was found exclusively breast-fed infants (92%) who did not receive vitamin K prophylaxis at birth (90%). Bleeding and pallor were the common features. The occurrence of intracranial hemorrhage was strikingly high (82%); the fatality rates was 24%. However, the fatality rate among patients receiving either 1 mg of vitamin K, intramuscularly, (17%) or 2 mg, orally, (18%) were lower than those not receiving vitamin K prophylaxis (36%). The incidence of IVKDI significantly declined to 4.2-7.8 per 100,000 births between 1988 to 1995 which was in reverse proportion to the coverage of vitamin K prophylaxis (r = -0.94, p < 0.05).

Topics: Administration, Oral; Breast Feeding; Female; Hemorrhage; Hospitals; Humans; Incidence; Infant; Infant, Newborn; Injections, Intramuscular; Male; Surveys and Questionnaires; Thailand; Vitamin K; Vitamin K Deficiency

A retrospective study is presented of the clinical features and outcome of late onset haemorrhagic disease due to vitamin K deficiency in 11 babies who were admitted to the emergency or child neurology unit during a 4-year period (January 1994-December 1997). The disease occurred in infants between 30 and 119 days of age (mean: 56+/-24 days). None of them received vitamin K after birth and all were breastfed. The presenting complaints were seizures (91%), drowsiness (82%), poor sucking (64%), vomiting (46%), fever (46%), pallor (46%), acute diarrhoea (27%), irritability and high-pitched cry (18%). On examination, tense or bulging fontanelle (73%), anisocoria (36%), weak neonatal reflexes (18%), cyanoses (18%) were the most frequent findings. The localizations of the intracranial haemorrhage were as follows: intracerebral (91%), subarachnoid (46%), subdural (27%), and intraventricular (27%). No fatality was observed. However, after a follow-up period ranging from 6 to 48 months (mean: 21+/-13 months), only three (27%) infants remained neurologically normal. Seizure disorders (73%), severe psychomotor retardation (46%), cerebral palsy (46%) and microcephaly (46%) were observed in the remainder. Hydrocephalus developed in three (27%) babies but none of them required shunt replacement. The value is emphasized of vitamin K prophylaxis in the newborn to reduce the incidence of late onset intracranial haemorrhage and handicap in children.

Topics: Follow-Up Studies; Humans; Infant; Intracranial Hemorrhages; Retrospective Studies; Tomography, X-Ray Computed; Vitamin K; Vitamin K Deficiency

Atrophic gastritis patients have intestinal bacterial overgrowth which could produce menaquinones. The aim of this study was to evaluate the interaction between a diet low in phylloquinone and minidoses of warfarin in subjects with and without bacterial overgrowth. Subjects with atrophic gastritis (indicated by serum pepsinogen ratio) and healthy volunteers were studied while fed a restrictive phylloquinone diet and while receiving a minidose of warfarin. Coagulation times, serum osteocalcin, serum undercarboxylated osteocalcin, plasma phylloquinone, plasma K-epoxide, plasma undercarboxylated prothrombin (PIVKA)-II and urinary gamma-carboxyglutamic acid (Gla) were measured. At baseline, there were no differences between groups for any variable measured. Comparisons between baseline and post intervention in both groups, showed significant increases in circulating levels of K-epoxide, PIVKA II and undercarboxylated osteocalcin. However, no differences were observed when comparisons were made between groups. Our data do not support the hypothesis that bacterial synthesis of menaquinones in patients with bacterial overgrowth due to atrophic gastritis confers considerable resistance to the effect of warfarin.

Topics: Aged; Anticoagulants; Bacteria, Anaerobic; Diet; Female; Food-Drug Interactions; Gastritis, Atrophic; Humans; Hydrogen-Ion Concentration; Intestines; Male; Middle Aged; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Warfarin

Using the rat as an experimental animal model we have found that prothrombin synthesis reaches its maximal level at a relatively low dietary vitamin K intake. At still higher vitamin K intakes, however, the urinary Gla-excretion was substantially increased, showing a different vitamin K requirement for liver and extrahepatic tissues. The increased urinary Gla-excretion was found for both phylloquinone and menaquinone-4, but not for menaquinone-8, which questions the bioavailability of higher menaquinones for extrahepatic tissues. A discrepancy was found between effects of nutritional vitamin K-deficiency and treatment with a vitamin K-antagonist (brodifacoum). With both regimens plasma prothrombin rapidly decreased to well below 10% of the starting values, but in case of K-deficiency urinary Gla had hardly decreased in 7 days, whereas after 3 days of brodifacoum treatment Gla-excretion had decreased to 17% of the starting values. An explanation for this observation is that prothrombin procoagulant activity does not decrease proportional to the prothrombin Gla-content, but that a wide range of undercarboxylated prothrombins have lost nearly all activity. During vitamin K-deficiency the remaining low levels of vitamin K would mainly give rise to undercarboxylated prothrombin, whereas during brodifacoum treatment only non-carboxylated prothrombin is formed. It seems plausible that in the latter case the urinary Gla originates from proteins with long half-life times, such as the bone Gla-proteins.

Topics: 1-Carboxyglutamic Acid; 4-Hydroxycoumarins; Animals; Anticoagulants; Diet; Dose-Response Relationship, Drug; Male; Prothrombin; Rats; Vitamin K; Vitamin K Deficiency

Topics: Female; Humans; Infant; Infant, Newborn; Male; Risk Factors; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Vitamin K is involved in the biosynthesis of a number of blood coagulation factors and bone proteins. It has been suggested that the vitamin K requirement of bone tissue is higher than that of the liver. Here we report that in rats very high doses of vitamin K affected neither the blood coagulation characteristics nor the blood platelet aggregation rate. This was observed for both phylloquinone and menaquinone-4. Both vitamers were also tested for their effects on the arterial thrombosis tendency in the rat aorta loop model. The mean obstruction times were prolonged at a high intake of menaquinone-4 (250 mg/kg body weight/day), and shortened after a similarly high phylloquinone regimen. Since (a) both vitamers only differ in their aliphatic side chains; and (b) a similar trend was observed after administration of phytol and geranylgeraniol, we conclude that the modulation of the arterial thrombosis tendency is accomplished by the side chain of vitamin K.

Topics: Animals; Blood Coagulation; Diet; Dietary Fats, Unsaturated; Disease Models, Animal; Disease Susceptibility; Diterpenes; Dose-Response Relationship, Drug; Male; Phytol; Platelet Aggregation; Rats; Rats, Wistar; Thrombosis; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

Racemic sodium warfarin, Coumadin, is widely used in the prevention of thromboembolic disease. The present study was undertaken to characterize three novel classes of warfarin analogs, and to compare them with the warfarin enantiomers. All three classes of compounds inhibit vitamin K epoxide reductase, the enzyme inhibited by racemic warfarin. The alcohol and the ester analogs have reduced protein binding compared with R-(+)-warfarin. The ester and the fluoro-derivatives have similar in vivo anticoagulant activity in the rat to that of S-(-)-warfarin. Thus, it is possible to synthesize novel warfarin analogs that differ from racemic warfarin or its enantiomers in certain selected properties.

Topics: Animals; Anticoagulants; Humans; Male; Microsomes, Liver; Mixed Function Oxygenases; Rats; Rats, Sprague-Dawley; Stereoisomerism; Structure-Activity Relationship; Vitamin K; Vitamin K Deficiency; Vitamin K Epoxide Reductases; Warfarin

Three unrelated infants presented with radiographic punctate calcifications, nasal hypoplasia, and abnormalities of the spine. Additional anomalies included cupped ears in 2 patients and one each with Dandy-Walker malformation with hydrocephaly, congenital cataracts, and peripheral pulmonary artery stenosis. The mothers of these 3 patients had chronic conditions associated with intestinal malabsorption requiring total parenteral nutrition for varying periods of time. The underlying causes of malabsorption were celiac disease, short bowel syndrome secondary to surgical resection, and jejuno-ileal bypass, respectively. Bleeding diathesis occurred in one mother requiring vitamin K supplementation during the second and third trimesters of pregnancy. We speculate that the chondrodysplasia punctata and other abnormalities in these children were caused by an acquired maternal vitamin K deficiency manifested during early pregnancy. However, the involvement of other vitamin deficiencies cannot be excluded. Thus, vitamin K deficiency of the embryo secondary to maternal malabsorption appears to be a third vitamin K-related mechanism leading to chondrodysplasia punctata in addition to warfarin embryopathy and epoxide reductase deficiency (pseudo-warfarin embryopathy).

Topics: Abnormalities, Drug-Induced; Anticoagulants; Child, Preschool; Chondrodysplasia Punctata; Female; Fetal Diseases; Humans; Infant; Infant, Newborn; Magnetic Resonance Imaging; Malabsorption Syndromes; Pregnancy; Pregnancy Complications; Radiography; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Health Policy; Humans; Infant, Newborn; Vitamin K; Vitamin K Deficiency

To clarify the origin of organ menaquinone-4 (MK-4), the distributions of phylloquinone and MK-4 were investigated in rats fed diets containing phylloquinone, MK-4 or menadione (1.1, 2.2 and 31 mumol/kg diet, respectively, 6 rats per group). Warfarin (2 x 1 mg/kg subcutaneously) was given (3 rats per group) to study the effect of vitamin K cycle blockage. In rats fed phylloquinone the vitamin accumulated mainly in liver and heart. Additionally, the diet resulted in significantly higher organ MK-4 concentrations compared with the vitamin K-deficient controls. The epoxide of MK-4 also was significantly higher in some organs. The MK-4 diet increased MK-4 concentration primarily in the heart, liver and lung. Rats fed menadione had significantly higher MK-4 and MK-4 epoxide concentrations in all organs examined. The greatest accumulations were in nonhepatic organs, particularly the pancreas, salivary gland and brain. Generally, liver and plasma had low MK-4 concentrations. Warfarin treatment lowered significantly the MK-4 concentrations, whereas MK-4 epoxide accumulated. The study shows the following: 1) dietary phylloquinone is accumulated mainly in the heart and liver, 2) the MK-4 accumulation in nonhepatic organs is due to synthesis rather than uptake and 3) MK-4 rather than phylloquinone may be the functional vitamin in nonhepatic organs.

Topics: Animals; Brain Chemistry; Liver; Lung; Male; Myocardium; Pancreas; Rats; Rats, Wistar; Salivary Glands; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Warfarin

To determine the prevalence of vitamin K deficiency bleeding in the Netherlands, in order to evaluate the efficacy of recommendations on vitamin K prophylaxis.. Descriptive.. University Hospital Nijmegen, the Netherlands.. Active surveillance of vitamin K deficiency bleeding (VKDB) by the Dutch Paediatric Surveillance Unit from October 1, 1992 to December 31, 1994.. Of the 19 reported cases 5 could be validated as late vitamin K deficiency bleeding: 2 idiopathic cases, and 3 secondary cases due to liver disorders. One case had intracranial bleeding and died. None of the cases had received exactly the recommended prophylaxis. The incidence of late VKDB was calculated to be 1.1/100,000 live births. Before vitamin K prophylaxis was recommended the incidence was estimated to be 7/100,000.. The present Dutch recommendations for prevention of vitamin K deficiency bleeding-1 mg vitamin K at birth and thereafter for breastfed infants daily 25 micrograms from 2 to 13 weeks-appear effective.

Topics: Cerebral Hemorrhage; Epistaxis; Hematemesis; Humans; Infant; Infant, Newborn; Vitamin K; Vitamin K Deficiency

A 7-week old, male infant died from an intracerebral haemorrhage due to vitamin K deficiency. He had been exclusively breast-fed. Directly after birth no vitamin K was administered. From day 10 a daily dose of 25 microgram vitamin K was given orally. At post mortem a mild cholestasis was found which may have been an additional factor contributing to late vitamin K deficiency.

Topics: Breast Feeding; Cerebral Hemorrhage; Fatal Outcome; Humans; Infant; Male; Vitamin K; Vitamin K Deficiency

Topics: Erythroblastosis, Fetal; Humans; Infant, Newborn; Leukemia; Neoplasms; Vitamin K; Vitamin K Deficiency

To confirm or refute a possible association of parenteral vitamin K prophylaxis and childhood cancer.. Population based case-control study. Comparison of vitamin K exposure in children with leukaemia or other common tumours with two control groups.. State of Lower Saxony (north western part of Germany); case recruitment from the German childhood cancer registry.. 272 children with leukaemia, nephroblastoma, neuroblastoma, rhabdomyosarcoma, and tumours of the central nervous system diagnosed between 1 July 1988 and 30 June 1993; children were aged between 30 days and 15 years at diagnosis. 334 population based controls without diagnoses of cancer matched to the leukaemia cases for age and sex.. Parenteral vitamin K prophylaxis (intramuscular and subcutaneous) versus oral and no vitamin K prophylaxis.. An association between parenteral vitamin K exposure and childhood cancer (leukaemias and other tumours combined) could not be confirmed (odds ratio 1.04, 95% confidence interval 0.74 to 1.48). For leukaemias the observed odds ratio was only 0.98 (0.64 to 1.50) (comparison of leukaemia cases with local controls 1.24 (0.68 to 2.25); state controls 0.82 (0.50 to 1.36)). These odds ratios remained almost unchanged when several potential confounders were considered in the logistic regression model.. This population based study adds substantial evidence that there is no association between parenteral vitamin K and childhood cancer.

Topics: Adolescent; Case-Control Studies; Central Nervous System Neoplasms; Child; Child, Preschool; Female; Germany; Humans; Infant; Infant, Newborn; Injections, Intramuscular; Injections, Subcutaneous; Kidney Neoplasms; Leukemia; Male; Neoplasms; Neuroblastoma; Population Surveillance; Rhabdomyosarcoma; Risk Factors; Vitamin K; Vitamin K Deficiency; Wilms Tumor

Clinical signs of vitamin K deficiency have been observed in cats offered two commercial canned diets high in salmon or tuna. Some of the queens and kittens offered these diets had died while survivors had increased coagulation times. Necropsies revealed hepatic and, or, gastrointestinal haemorrhages. Coagulation times of survivors returned to normal after vitamin K therapy. The purpose of this study was to induce a vitamin K deficiency in kittens and determine the dietary requirement. Kittens were offered vitamin K-deficient purified diets containing antibiotics and, or, substances inherent in canned fish diets that may have contributed to the deficiency. Clinical signs of vitamin K deficiency were not observed, even though one purified diet contained only 4 micrograms K1/kg diet compared with 60 micrograms in the commercial tuna diet. Therefore, a minimum vitamin K requirement could not be determined using purified diets; nevertheless, canned commercial diets formulated primarily with fish should contain more than 60 micrograms K1/kg diet.

Topics: Animals; Blood Coagulation; Cats; Chromatography, High Pressure Liquid; Diet; Female; Fishes; Food Analysis; Male; Nutritional Requirements; Tuna; Vitamin K; Vitamin K Deficiency

To compare three methods of vitamin K prophylaxis for neonatal vitamin K deficient intracranial haemorrhage.. We designed three strategies for vitamin K prophylaxis: 1. therapeutic administration of vitamin K in a mass screening system using the hepaplastin test; 2. routine oral administration of vitamin K to newborn infants; and 3. administration of vitamin K to lactating mothers during the late neonatal period in addition to the routine method. We evaluated the efficacy of these methods by determining hepaplastin test values at the first month of age.. 66,076 full term healthy newborn infants without any complications.. Of 55,513 infants in the mass screening system, 3068 infants received vitamin K therapeutically. At the first month of age, in the group where vitamin K was administered therapeutically, 56 infants (1.83%) exhibited low hepaplastin test values (< 40%) despite vitamin K administration. But extremely low values (< 20%), indicating a very high risk of neonatal intracranial haemorrhage, were observed in 34 (0.06%) of 52,445 infants who did not receive vitamin K. In the routine administration system, oral administration of vitamin K twice within the first week of life showed a lower incidence (0.19%) of low level cases than a single administration (1.56%). An additional administration of vitamin K to lactating mothers throughout the late neonatal period showed an effective result.

Topics: Administration, Oral; Cerebral Hemorrhage; Clinical Protocols; Female; Humans; Infant; Infant, Newborn; Japan; Mass Screening; Neonatal Screening; Perinatal Care; Pregnancy; Prenatal Care; Treatment Outcome; Vitamin K; Vitamin K Deficiency

A Danish surveillance group established after the introduction of oral vitamin K prophylaxis monitored Danish cases with late onset vitamin K deficiency bleeding by regular questionnaires to all paediatric departments. Six cases were reported, one of whom died and three are severely handicapped. All cases occurred among an estimated 134,500 infants given a single oral 1 mg vitamin K dose at birth. No cases have been reported so far during the existent regimen: 2 mg at birth and 1 mg weekly orally administered vitamin K during the first 3 months of life, given to at least 163,000 infants. The present study is concordant with the only other study on weekly peroral prophylaxis published. We consider the mentioned weekly regimen safe and appropriate.

Topics: Administration, Oral; Denmark; Drug Administration Schedule; Humans; Infant; Infant, Newborn; Vitamin K; Vitamin K Deficiency

Topics: Adult; Age Factors; Blood Coagulation Factors; Celiac Disease; Humans; Male; Prothrombin; Tomography, X-Ray Computed; Vitamin K; Vitamin K Deficiency

Topics: Biliary Atresia; Blood Coagulation Disorders; Breast Feeding; Cerebral Hemorrhage; Humans; Infant; Infant, Newborn; Injections, Intramuscular; Vitamin K; Vitamin K Deficiency

Topics: Glycine max; Humans; Infant; Infant Food; Infant, Newborn; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Protein-bound gamma-carboxyglutamate (Gla) has been demonstrated in calcified atherosclerotic plaques. Vitamin K is required for the formation of Gla-residues. As the biological activity of Gla-proteins appears to be strictly dependent on the presence of the Gla-residues, vitamin K status may be an important factor in the development and progression of atherosclerotic calcifications. We studied the association of vitamin K status, as assessed by nutritional vitamin K intake and the measurements of two circulating immunoreactive osteocalcin (irOC) fractions, with aortic atherosclerosis in a population-based study of 113 postmenopausal women. Women with calcified lesions (n = 34) had a 42.9 micrograms lower mean age-adjusted dietary vitamin K intake/day (95% C.I. -6.6 to 92.5) than those without calcifications (n = 79). Atherosclerotic women had higher irOC levels with a low affinity for hydroxyapatite (irOCfree): age-adjusted difference of 0.32 ng/ml (95% C.I. 0.03 to 0.61). In addition, the high affinity irOC levels expressed as a percentage (hydroxyapatite binding capacity, HBC) were 5.12% (95% C.I. 1.32 to 8.92) lower in women with calcifications. Our study indicates that women with aortic atherosclerosis have an impaired vitamin K status as reflected by a lower nutritional vitamin K intake, an increased irOCfree level and a reduced HBC level. An impaired vitamin K status in subjects with atherosclerosis is compatible with the view that vitamin K or Gla-containing proteins are involved in the development of calcification of the vessel wall.

Topics: 1-Carboxyglutamic Acid; Aged; Aorta, Abdominal; Aortic Diseases; Arteriosclerosis; Body Constitution; Body Mass Index; Calcinosis; Chromatography, Affinity; Cohort Studies; Diet; Durapatite; Female; Humans; Middle Aged; Osteocalcin; Vitamin K; Vitamin K Deficiency

Rats were made vitamin K-deficient by feeding them a diet devoid of vitamin K and by rigorously preventing coprophagy. After one week, circulating prothrombin concentrations were between 5 and 10% of initial values, and various amounts of phylloquinone, menaquinone-4, and menaquinone-9 were given in a single dose either subcutaneously, orally, or colorectally. The relative 'vitamin K activities' of these compounds were assessed by comparing their ability to support prothrombin synthesis after subcutaneous injection. Intestinal and colonic absorption were deduced from the difference between subcutaneous and either oral or colorectal administration of the vitamers. It is concluded that the colonic absorption of all three forms of vitamin K is extremely poor, suggesting that physiological menaquinones in the colon do not contribute substantially to vitamin K status in rats. Furthermore, the stimulation of prothrombin synthesis by menaquinone-9 lasted much longer than that by the two other K-vitamers, resulting in a substantially higher 'vitamin K activity' of menaquinone-9.

Topics: Animals; Biological Availability; Hemostatics; Intestinal Absorption; Male; Prothrombin; Rats; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

Oral administration of vitamin K was reported to increase bone mineral density. However, the possible role of vitamin K in the pathogenesis of osteoporosis still remains unclear. Therefore, we measured the serum concentration of vitamin K1 and K2 (menaquinone-4, 7, 8) in 24 elderly women with osteoporotic vertebral compression fracture and in 36 elderly women without fracture. Major forms of vitamin K present in sera in this study were vitamin K1 and menaquinone-7. On the other hand, serum menaquinone-4 and -8 were undetectable in most women. Serum concentration of menaquinone-7 was significantly lower in women with fracture than in those without fracture (3.29 +/- 3.63 ng/ml vs 6.26 +/- 5.62, mean +/- SD, respectively), while no difference was found in serum vitamin K1 concentration (0.837 +/- 0.620 ng/ml vs 0.820 +/- 0.686, respectively). There was no difference between both groups in background data such as age, body height, body weight, and body mass index, as well as serum level of calcium, inorganic phosphate, creatinine, albumin, and alkaline phosphatase. These results suggest the possibility that deficiency of vitamin K, particularly that of menaquinone-7, is one of the risk factors for developing osteoporosis.

Topics: Aged; Female; Fractures, Stress; Humans; Osteoporosis, Postmenopausal; Vitamin K; Vitamin K Deficiency

We developed a RIA involving a polyclonal antibody against bovine osteocalcin, which has a carboxy-terminal epitope. Although the antibody recognizes both native and descarboxy osteocalcin, the two forms of osteocalcin were differentiated by adsorption to barium sulfate, taking advantage of the calcium-binding properties of the vitamin K-dependent gla domain. To test the clinical application of undercarboxylated osteocalcin, we examined the effect of minidose warfarin on this measure in nine healthy subjects, ages 60 to 80 years. The percentage of undercarboxylated osteocalcin increased by 170% +/- 36% (mean +/- SE) after 7 days of treatment with warfarin, 1 mg/day. The effectiveness of undercarboxylated osteocalcin as a sensitive measure of vitamin K nutritional status was further established when concentrations dropped to 17% +/- 14% below baseline with 2 days of repletion with vitamin K1, 5 mg/day, during which prothrombin times did not leave the normal range.

Topics: Adsorption; Aged; Barium Sulfate; Female; Humans; Male; Middle Aged; Nutritional Status; Osteocalcin; Vitamin K; Vitamin K Deficiency; Warfarin

A patient with primary biliary cirrhosis (PBC) developed marked hypoprothrombinemia with decreased concentrations of the vitamin K-dependent coagulation factors VII, IX, and X during treatment with rifampicin. The coagulation abnormalities were easily corrected by administration of vitamin K. Different mechanisms may be involved, such as a decreased production of menaquinones by intestinal bacteria, a warfarin-like effect by inhibition of the vitamin K epoxide reductase, or an increased oxidative degradation of vitamin K as a result of hepatic microsomal enzyme stimulation. Whatever the mechanism involved, the appearance of this complication in a patient with PBC probably points to the importance of a pre-existing poor vitamin K status. Patients with PBC, treated with rifampicin, should have a regular monitoring of their vitamin K status. Adequate vitamin substitution should be administered, if necessary.

Topics: Female; Humans; Hypoprothrombinemias; Liver Cirrhosis, Biliary; Middle Aged; Prothrombin Time; Rifampin; Vitamin K; Vitamin K Deficiency

Topics: Administration, Oral; Health Policy; Humans; Infant, Newborn; Injections, Intramuscular; Prospective Studies; Retrospective Studies; Vitamin K; Vitamin K Deficiency

Topics: Administration, Oral; Germany; Humans; Infant, Newborn; Surveys and Questionnaires; Treatment Outcome; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Deficiencies of the vitamin K-dependent coagulation factors were identified in a Devon rex cat which had bled after castration. Haemorrhage was controlled by plasma transfusion. Clotting times were normalised by oral administration of vitamin K. This report confirms the existence of this bleeding disorder in a Devon rex cat in the United Kingdom.

Topics: Administration, Oral; Animals; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Castration; Cat Diseases; Cats; Hemorrhage; Male; Partial Thromboplastin Time; Postoperative Complications; Prothrombin Time; Vitamin K; Vitamin K Deficiency

It is unclear whether menaquinones produced by the intestinal microflora play any role in human nutrition. Reports of coagulopathy due to vitamin K deficiency occurring in patients receiving broad spectrum antibiotics indirectly suggest that vitamin K2 produced by the gut microflora may be utilized by the host. We analyzed the vitamin K1 (phylloquinone) and vitamin K2 (menaquinone) content in a convenience sample of 22 human post-mortem liver samples, including 9 individuals who had been receiving broad spectrum antimicrobials prior to death and 13 individuals who had been victims of sudden, unexpected deaths. There were no significant differences in the mean (+/- SEM) phylloquinone content between the 2 groups [21.9 (+/- 15.5) vs. 16.0 (+/- 9.3) pmol/g wet weight (excluding those who had received supplemental vitamin K1)] but there was a significant difference (p < 0.05) in the total menaquinone (MK) content, 70.0 (+/- 23.3) vs. 423.1 (+/- 141) pmol/g between the 2 groups. These findings suggest an association between receipt of broad spectrum antibiotics and a reduction in hepatic menaquinone concentration, lending support to the hypothesis that a reduction in the gut microflora responsible for their production leads to reduced hepatic stores of this form of the vitamin.

Topics: Adult; Aged; Anti-Bacterial Agents; Cadaver; Female; Humans; Intestines; Liver; Male; Middle Aged; Vitamin K; Vitamin K 1; Vitamin K Deficiency

Topics: Administration, Oral; Drug Administration Schedule; Hemorrhage; Humans; Infant, Newborn; Population Surveillance; Vitamin K; Vitamin K Deficiency

The effects of menatetrenone (2-methyl-3-tetraprenyl-1,4-naphthoquinone, MK-4) on calcium balance were studied in male Sprague-Dawley rats. Experiment 1: Rats in metabolic cages that were fed a vitamin K-deficient diet and injected daily with latamoxef (100 mg/kg, i.p.) were either treated or untreated with MK-4 for 7 days. Daily food intake, urine volume and feces weight were determined, and calcium concentration in these samples was measured. Calcium balance was calculated as the difference between calcium intake and urinary and fecal calcium excretion. Cumulative calcium balance in the vitamin K-deficient group treated with latamoxef was lower than that in normal rats; this balance was significantly improved by MK-4 (1 and 10 mg/kg, s.c.) administered for 7 days. Experiment 2: Rats were fed a vitamin K-deficient diet containing 4.6% sodium chloride for 6 weeks. MK-4 was administered as a dietary supplement. Forty-eight-hour calcium balance, determined once a week, was significantly reduced compared with that of normal rats after 3 and 5 weeks; the balance was restored dose-dependently by MK-4 administration (1 and 10 mg/kg). Experiment 3: Rats were subjected to the same experimental conditions as experiment 2 for 6 weeks, and intestinal calcium transport was determined using an everted gut-sac technique. Calcium transport was reduced by the high sodium, vitamin K-deficient diet, and this reduction was restored by MK-4 administration (10 mg/kg). These results suggest that MK-4 improves the reduced calcium balance by increasing intestinal calcium absorption in these rats.

Topics: Alkaline Phosphatase; Animals; Blood Coagulation; Calcium; Diet; Hemostatics; Intestinal Absorption; Intestinal Mucosa; Intestines; Kidney Function Tests; Male; Phosphates; Rats; Rats, Sprague-Dawley; Sodium; Vitamin K; Vitamin K 2; Vitamin K Deficiency

Topics: Biomarkers; Breast Feeding; Female; Humans; Infant; Infant, Newborn; Protein Precursors; Prothrombin; Vitamin K; Vitamin K Deficiency

Topics: Bottle Feeding; Humans; Infant, Newborn; Risk Factors; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Health Policy; Humans; Infant, Newborn; Organizational Policy; Patient Compliance; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

A prospective study of some coagulation screening tests in newborns is performed having in mind to elucidate coagulation status in healthy term newborns and the necessity of vitamin K prophylaxis. Two groups of newborn babies are formed: the first includes 29 babies without vit. K prophylaxis, the second--30 newborns who receive 1 mg/kg i.m. vit. K on the first day after birth. All the newborns have their prothrombin time (PT) and partial prothrombin time (aPTT) measured in day first, fourth, and in a small number on the seventh day as well. Low PT (54%) and moderately prolonged PTT (44.37 sec) are found on the first day after birth. It is established that the coagulation status is normalized faster in newborns who have received vit. K prophylaxis--as soon as fourth day, while the group without vit. K--until the end on the first or the beginning of the second week. The conclusion is made that it is wise to use vit. K prophylaxis not only with premature, but also in risk term infants.

Topics: Analysis of Variance; Blood Coagulation; Blood Coagulation Tests; Female; Humans; Infant, Newborn; Male; Reference Values; Vitamin K; Vitamin K Deficiency

Patients undergoing hematopoietic stem cell transplantation (HSCT) are dependent on i.v. vitamin K supplementation to prevent deficiency. Vitamin K deficiency may contribute to the development of a hypercoagulable state by limiting hepatic synthesis of fully functional carboxylated anticoagulant protein C (PC). The ratio of PC antigen (CAg) to PC measured in a clot-based functional assay (CFx) reflects the degree to which PC is carboxylated. The 133 patients undergoing HSCT received vitamin K 10 mg per week (low dose, 101 patients) or 5 mg per day (high dose, 32 patients) i.v. as their sole exogenous source of vitamin K. CAg and CFx were assayed before HSCT preparative regimen and again 14 days later. CAg and CFx fell significantly in both groups from day 0 to day 14 but there were no differences between the low-dose and high-dose vitamin K groups. For both groups, CAg correlated strongly with CFx at day 14 (p = 0.0001). At day 14, the CAg/CFx ratio for the low-dose group was significantly greater than for the high-dose group (1.26 +/- 0.4 vs 1.09 +/- 0.1, p < 0.0002), suggesting that low-dose patients had a higher proportion of incompletely carboxylated PC. The CAg/CFx ratio at day 14 correlated with serum albumin for the high-dose group (p = 0.05), but not the low-dose group (p = 0.09), suggesting that the change in ratio in the low-dose group was not simply due to a lack of protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antigens; Bone Marrow Transplantation; Dose-Response Relationship, Drug; Hematopoietic Stem Cell Transplantation; Humans; Injections, Intravenous; Protein C; Protein C Deficiency; Vitamin K; Vitamin K Deficiency

Rats were made vitamin K-deficient by feeding them a 1:1 (w/w) mixture of a commercial vitamin K-depleted diet and boiled white rice. After one week of treatment the rats had developed severe vitamin K deficiency, resulting in Thrombotest values of 5-10% of the initial values. In this experimental system the efficacy of phylloquinone (K1) was compared with that of menaquinone-4 (MK-4) by measuring the extent to which the Thrombotest was normalized after the administration of varying doses of the respective vitamins. Oral administration of the vitamins showed that the efficacy of K1 was at least two-fold higher than that of MK-4. As comparable results were obtained after subcutaneous administration of the vitamins, we conclude that after oral administration the intestinal absorption had been quick and nearly complete. A less pronounced effect of K1 and MK-4 was found after colorectal administration. For both forms of vitamin K relatively high amounts (well above the physiological concentration) were required before significant effects on the Thrombotest could be observed. Therefore these data demonstrate the importance of sufficient dietary vitamin K consumption in rats. The efficacy of other menaquinones may be investigated in the same experimental animal model system.

Topics: Administration, Oral; Animals; Blood Coagulation Factors; Injections, Subcutaneous; Male; Rats; Rats, Inbred Lew; Rectum; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

Vitamin K prophylaxis has been developed to prevent classic haemorrhagic disease of the newborn. Single vitamin K administration after birth has been reported to fail, resulting in late haemorrhagic disease of the newborn. The preventive effect of oral administration of vitamin K1 1 mg, repeated weekly during the first three months of life, was studied in 48 healthy breast-fed infants, by determination of thrombotest, PIVKA-II and vitamin K1 concentrations at the age of 4, 8 and 12 weeks. All infants showed normal thrombotest values and PIVKA-II was not detectable. Vitamin K1 concentrations were negatively correlated with the number of days elapsed since the most recent vitamin K administration. Six to seven days after the latest application, mean levels were 1223, 927 and 748 pg/ml at ages 4, 8 and 12 weeks, respectively. In conclusion, weekly administration of vitamin K1 1 mg offers complete protection against vitamin K deficiency and does not result in an accumulation of vitamin K1 in the blood.

Topics: Biomarkers; Blood Proteins; Breast Feeding; Drug Evaluation; Female; Humans; Infant; Infant, Newborn; Male; Protein Precursors; Prothrombin; Prothrombin Time; Time Factors; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Administration, Oral; Humans; Infant, Newborn; Injections, Intramuscular; Neoplasms; Risk Factors; Vitamin K; Vitamin K Deficiency

The null hypothesis of our study is that the incidence of vitamin K deficiency in mother-infant pairs exposed to anticonvulsant drugs is not higher than in controls.. In this multicenter observational case-control study, 25 pregnant women receiving anticonvulsant therapy and 25 pregnant controls were studied for PIVKA-II (protein induced by vitamin K absence of factor II) and vitamin K1 concentrations at 32 weeks' gestation and at delivery.. PIVKA-II was detectable in 54% of cord samples of the anticonvulsant group and in 20% of controls (chi 2, p = 0.01). In both groups vitamin K1 cord blood levels were predominantly below the detection limit. Maternal vitamin K1 concentrations were lower in women with epilepsy than in controls (Wilcoxon's rank sum test, p < 0.05), but PIVKA-II was rarely present.. The incidence of vitamin K deficiency is increased in neonates exposed to anticonvulsant drugs prenatally. Their mothers, however, are rarely vitamin K deficient.

Topics: Anticonvulsants; Biomarkers; Case-Control Studies; Epilepsy; Female; Fetal Blood; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Protein Precursors; Prothrombin; Vitamin K; Vitamin K Deficiency

To determine the relationship between vitamin K dependent coagulation factors and natural anticoagulants, namely protein C and protein S, in various degrees of vitamin K deficiency, plasma values for clotting activity, protein induced by vitamin K absence (PIVKA-II), protein C antigen, gamma-carboxy protein C antigen, and protein S antigen including total and free fractions and activity of protein C were measured in 66 full term and healthy breast fed neonates who did not receive vitamin K supplement at birth. The 66 neonates were divided into a control group (17 cases) and a low group (49 cases) according to their values for clotting activity--that is, > or = 20% or < 20% during the first six days of life--and vitamin K was immediately given when the neonates showed values < 20%. In the low group clotting activity gamma-carboxy protein C, free protein S, and protein C activity was significantly decreased to a minimum on day 2 or 3, and increased in parallel after vitamin K administration. Furthermore, they were positively correlated with one another and inversely cor-correlated with the PIVKA-II concentrations. These findings suggest that simultaneous gamma-carboxylation of coagulation factors and proteins C and S acts to maintain both coagulation and anticoagulation activities in parallel at various concentrations of vitamin K. The breast milk intake in the group with low values of clotting activity was significantly lower than that in the control group during the first three days of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Biomarkers; Blood Coagulation Factors; Humans; Infant Nutritional Physiological Phenomena; Infant, Newborn; Milk, Human; Protein C; Protein Precursors; Protein S; Prothrombin; Vitamin K; Vitamin K Deficiency

After optimizing conditions for maximal production of menaquinones (MK), S. aureus and B. vulgatus were grown in batches, harvested and extracted for qualitative and quantitative MK content utilizing HPLC (high performance liquid chromatography) until a total of 6 mg was available. Five normal healthy male volunteers were placed on a vitamin K1 deficient diet (< or = 25 micrograms/day) and were subsequently warfarinized to maintain a prothrombin time (PT) 1.5-2 times control. Following stabilization of daily warfarin dosage 1 mg doses of the extracted MK were orally administered. As a control, the same volunteers were later warfarinized but no MK was given. Within 24 h of MK administration the prothrombin time (PT) decreased (mean +/- SEM) 3.6 +/- 1.0 s (p < 0.005) and the Factor VII level increased 0.36 +/- 0.3 u/ml (p < 0.005) vs a PT increase of 1.0 +/- 1.0 s (p > 0.1) and a Factor VII level increase of 0.03 +/- 0.1 u/ml (p > 0.1) in the control phase. Within 48 h of MK administration the PT was normal in all subjects but remained > or = 1.5 times control in the control phase. These data demonstrate for the first time the absorption and bioactivity of bacterially synthesized vitamin K in humans.

Topics: Administration, Oral; Adult; Bacteroides; Factor VII; Humans; Intestinal Absorption; Male; Prothrombin; Prothrombin Time; Staphylococcus aureus; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Warfarin

A subclinical vitamin K deficiency was induced in 32 healthy subjects (four groups of eight males and females) aged 20-40 and 60-80 yr residing in the Metabolic Research Unit of the Human Nutrition Research Center on Aging at Tufts University. Volunteers were initially fed (4 d) a baseline-period diet containing the recommended daily allowance for vitamin K which is equivalent to 80 micrograms/d of phylloquinone (vitamin K1). During the baseline period various parameters of vitamin K nutritional status were monitored. The baseline period was followed by a 13-d depletion period during which the subjects were fed a very low vitamin K1 diet (approximately 10 micrograms/d). After depletion, the subjects entered a 16-d repletion period (four stages lasting 4 d each) during which time they were repleted with 5, 15, 25, and 45 micrograms of vitamin K1 per day. Vitamin K1 depletion dramatically and significantly decreased plasma vitamin K1 levels (P < 0.0001) in both elderly and young groups to values 13-18% of day 1 (elderly 0.22 nM, young 0.14 nM). Repleting the subjects with up to 45 micrograms of vitamin K1 per day failed, in the case of the young subjects, to bring plasma vitamin K1 levels back into the normal range. Dietary vitamin K1 restriction induced different responses in the urinary excretion of gamma-carboxyglutamic acid between the young and the elderly subjects with values decreasing significantly (P < 0.03) in the young while remaining unchanged in the elderly. The vitamin K1 depletion period had no significant effect on either prothrombin and activated partial thromboplastin times, or Factor VII and protein C (as determined by antigenic and functional assays). By using a monoclonal antibody, decarboxy prothrombin was found to increase slightly but significantly in both groups (P < 0.05) as a consequence of the low vitamin K1 diet. This study clearly shows that a diet low in vitamin K1 can result in a functional subclinical deficiency of vitamin K (decreased urinary gamma-carboxyglutamic acid excretion) without affecting blood coagulation.

Topics: 1-Carboxyglutamic Acid; Adult; Aged; Aged, 80 and over; Aging; Antigens; Diet; Factor VII; Female; Humans; Male; Middle Aged; Nutritional Status; Partial Thromboplastin Time; Protein C; Prothrombin Time; Vitamin K; Vitamin K Deficiency

Vitamin K prophylaxis is recommended to prevent the hazard of hemorrhage caused by vitamin K deficiency in young infants. A single administration after birth seems inadequate to completely prevent late haemorrhagic disease in breast-fed infants. The preventive effect of a daily oral dose of 25 micrograms vitamin K1, which is comparable to about half the dose ingested by formula-fed infants, was evaluated in 58 breast-fed infants. No clinical or biochemical signs of vitamin K deficiency occurred; PIVKA-II was not detectable, and vitamin K1 concentrations were moderately elevated. Vitamin K1 levels were negatively correlated with the number of hours elapsed since the most recent gift. Twenty to 28 h after the administration, median (P10-P90) levels were 1,262 (267-4,328), 1,072 (293-3,427), and 882 (329-2,070) pg/ml at 4, 8, and 12 weeks of age, respectively. Vitamin K1 levels in formula-fed infants (n = 10) were around 7,000 pg/ml. In conclusion, daily supplementation of 25 micrograms vitamin K1 can be recommended for breast-fed infants to prevent vitamin K deficiency beyond the neonatal period.

Topics: Biomarkers; Breast Feeding; Female; Humans; Infant, Newborn; Male; Protein Precursors; Prothrombin; Vitamin K; Vitamin K Deficiency

Topics: Animals; Fetal Blood; Humans; Infant Food; Infant, Newborn; Intestinal Absorption; Japan; Liver; Meconium; Milk; Milk, Human; Vitamin K; Vitamin K Deficiency

Topics: Administration, Oral; Animals; Germ-Free Life; Intestines; Male; Mice; Mice, Inbred ICR; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

The effect of menaquinone-4 (MK-4, vitamin K2) was studied on des-gamma-carboxy prothrombin (DCP or PIVKA-II) levels in three subjects with vitamin K deficiency and five patients with hepatocellular carcinoma (HCC) with positive DCP. The half-life of DCP in HCC patients after intravenous MK-4 administration (50 mg daily for 14 days) was determined to be 60 hours, identical to that found in vitamin K-deficient subjects who received MK-4. When a single dose of MK-4 (10 mg) was given intravenously to three patients with HCC and elevated DCP, the levels decreased with a reduction rate identical to that in vitamin K-deficient subjects for the first 1 to 3 days, followed by an increase reaching the previous level in 7 to 10 days. Changes in plasma coagulant activity were compared between subjects with vitamin K deficiency and those with HCC before and after a single dose of MK-4 (10 mg). The activity increased in DCP-positive patients with HCC as in vitamin K-deficient subjects who received the same single dose of MK-4. The increase was greater in HCC patients with higher DCP levels. These results suggest that the level of plasma DCP in patients with HCC responded to vitamin K with the same sensitivity as that in vitamin K-deficient subjects. When patients with HCC underwent effective tumor therapy (resection or arterial embolization), the reduction rate (slope of DCP decline) was found to be identical to that in vitamin K-deficient subjects given with MK-4. In patients with less effective therapy, the reduction rate was smaller, or there was an increase in DCP. These observations strongly suggest that sequential measurements of the DCP reduction rate after treatment for HCC are useful for assessing therapeutic effects.

Topics: Aged; Biomarkers; Carcinoma, Hepatocellular; Embolization, Therapeutic; Female; Half-Life; Humans; Liver Neoplasms; Male; Middle Aged; Protein Precursors; Prothrombin; Vitamin K; Vitamin K 2; Vitamin K Deficiency

The efficacy of vitamin K prophylaxis (1 mg im or sc, or 1-2 mg orally both given as a single dose at birth) in the prevention of vitamin K deficiency bleeding in early infancy was estimated in Germany during a 15-month period between 1988 and 1989. Cases were identified by a survey of all paediatric hospitals and population denominators by a survey of all obstetric hospitals. Response rates were 85% and 68%, respectively. Thirteen cases of vitamin K deficiency bleeding in early infancy with confirmed prophylactic states were confirmed, seven of whom had intracranial haemorrhage. The estimated efficacy of single parenteral administration of vitamin K versus no prophylaxis was 96.7% (95% confidence interval: 74-99.6%) and for single oral administration versus no prophylaxis 80.4% (9.1-95.6%). Single parenteral vitamin K prophylaxis gave substantial protection against vitamin K deficiency bleeding in early infancy. Single oral prophylaxis appeared to be less effective, although the difference was not significant, as indicated by the wide overlap of the respective 95% confidence intervals.

Topics: Administration, Oral; Germany; Humans; Infant; Infant, Newborn; Infusions, Parenteral; Surveys and Questionnaires; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Appearance of PIVKA-II (protein induced by vitamin K absence-II) in serum is a biochemical sign of insufficient vitamin K-dependent carboxylation of prothrombin. Plasma concentrations of PIVKA-II and vitamin K1 were determined in 24 children with cystic fibrosis. Eight were supplemented with vitamin K1. The purpose of the study was to determine the occurrence of vitamin K deficiency in cystic fibrosis and to evaluate the effect of vitamin K supplementation. PIVKA-II was detectable in only one unsupplemented child. In this patient, the concentration of vitamin K1 was below the limit of detection of 60 ng/l. Vitamin K1 levels in the other unsupplemented children were normal (mean 476 ng/l = 1 mmol/l). The supplemented patients showed extremely high levels of vitamin K1 (mean 22445 ng/l = 50 nmol/l). In conclusion, vitamin K deficiency occurs infrequently in cystic fibrosis. Checking the coagulation system is advised, but routine vitamin K supplementation is not recommended. If additional vitamin K is needed, the starting dose should not exceed 1 mg daily.

Topics: Adolescent; Adult; Child; Child, Preschool; Cystic Fibrosis; Decarboxylation; Female; Humans; Infant; Infant, Newborn; Male; Protein S; Prothrombin; Vitamin K; Vitamin K Deficiency

Topics: Cerebral Hemorrhage; Female; Humans; Infant, Newborn; Time Factors; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Administration, Oral; Hemothorax; Humans; Infant; Male; Vitamin K; Vitamin K Deficiency

Newborn infants are susceptible to bleeding disorders caused by a vitamin K deficiency, so called 'haemorrhagic disease of the newborn' (HDN). These bleedings often occur in infants after medication of the mother with antiepileptics, such as phenobarbital or phenytoin. It has been suggested that an increase in the late type of HDN in exclusively breast-fed infants might be related to the presence of cytochrome P450-inducing polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) in human milk. In order to study this possible mechanistic relationship 5-week-old, germfree, female WAG/Rij-rats were exposed to a single oral dose of either 1 microgram 2,3,7,8-tetrachlorodibenzo-p-dioxin/kg body weight (TCDD) or 30 mg 2,2',4,4',5,5'-hexachlorobiphenyl/kg body weight (HxCB), representing cytochrome P-450 1A (3-methylcholanthrene type) and 2B (phenobarbital type) inducers. During the experiment blood coagulation time from each rat was measured. Also, hepatic 7-ethoxy-(EROD) and 7-pentoxyresorufin O-dealkylating (PROD) activities and total cytochrome P450 content were measured. Blood coagulation time (Thrombotest) in the HxCB-treated rats was significantly prolonged and positively correlated to PROD activity and total P450 content. No clear effect of TCDD on coagulation time could be observed under these experimental conditions. These results suggest involvement of P450 2B isoenzymes in vitamin K metabolism.

Topics: Animals; Blood Coagulation; Body Weight; Cytochrome P-450 CYP1A1; Cytochrome P-450 CYP2B1; Cytochrome P-450 Enzyme System; Female; Gas Chromatography-Mass Spectrometry; Germ-Free Life; Liver; Microsomes, Liver; Organ Size; Oxidoreductases; Polychlorinated Biphenyls; Polychlorinated Dibenzodioxins; Prothrombin Time; Rats; Rats, Inbred Strains; Vitamin K; Vitamin K Deficiency

There is evidence that vitamin K-deficiency during human pregnancy can be caused by the therapeutic use of warfarin or phenytoin. The pregnancy histories of three cases of Binder's syndrome are reported. One was associated with warfarin exposure, one with phenytoin exposure and one with alcohol abuse. It is proposed that Binder's syndrome can be caused by prenatal exposure to agents that cause vitamin K-deficiency. Sprague-Dawley rats were treated from postnatal day 1 to 12 weeks with daily doses of warfarin (100 mg/kg) and concurrent vitamin K1 (10 mg/kg). This regimen creates a net extra-hepatic vitamin K-deficiency. The treated rats developed with a distinct facial appearance characterized by a markedly reduced snout. Histological examination showed that the normally non-calcified septal cartilage was extensively calcified. It is proposed that normal growth of the septal cartilage is necessary for the development of the profile of the nose and midface and that normal growth will only take place while the septal cartilage is uncalcified.

Topics: Adolescent; Alcoholism; Aneurysm, Ruptured; Animals; Cartilage; Child, Preschool; Female; Humans; Infant; Intracranial Aneurysm; Male; Maxilla; Nasal Bone; Nasal Septum; Phenytoin; Pregnancy; Pregnancy Complications, Cardiovascular; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Thrombophlebitis; Vitamin K; Vitamin K Deficiency; Warfarin

During recent years, we have observed two cases of haemorrhage due to vitamin K deficiency which developed late in the neonatal period. One patient was a female infant aged six weeks with severe intracranial bleeding and the other was a female infant aged three weeks with marked haemorrhage from the umbilicus. Both of these infants were entirely breast-fed and had received vitamin K (1 mg fytomenadion) orally at birth. Both infants had unrecognized alfa-1-antitrypsin deficiency with liver involvement. In other European countries, many cases of late haemorrhagic disease of the newborn due to vitamin K deficiency have been registered in infants who had received oral vitamin K prophylaxis. On the basis of these observations and investigations which suggest that oral vitamin K prophylaxis is not so effective as intramuscular administration, it is suggested that the present oral vitamin K prophylaxis should be altered.

Topics: Administration, Oral; Cerebral Hemorrhage; Female; Humans; Infant; Infant, Newborn; Radiography; Umbilicus; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Serum vitamin K concentrations and prothrombin induced by absence of vitamin K (PIVK-II) concentrations were assayed in 43 patients with cystic fibrosis. Twenty nine showed a normal PIVKA-II and vitamin K concentrations; 14 showed an increased PIVKA-II concentration, in one of whom serum vitamin K was decreased. Although their vitamin K concentrations were normal, some patients with cystic fibrosis still had an increased PIVKA-II. There was a significant correlation between PIVKA-II concentrations and the administration of antibiotics, a factor which has not previously been considered responsible for an increase in PIVKA-II.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Child; Child, Preschool; Cystic Fibrosis; Humans; Infant; Prothrombin; Vitamin E; Vitamin K; Vitamin K Deficiency

Liver and serum concentrations of vitamin K active compounds were measured in two groups of (deficient and normal) broilers after administration of phylloquinone 1 mg/kg. Assays were performed by HPLC after extraction and purification of these compounds. The only menaquinone found in the chicken was menaquinone-4. In the deficient group, the chickens exhibited hepatic concentrations of vitamin K1, vitamin K1 epoxide and menaquinone-4 markedly lower than those of the control group. After administration of phylloquinone, vitamin K and vitamin K epoxide levels fell sharply. There is no hepatic storage of vitamin K comparable to that of vitamin A. However, while menaquinone levels were found to be stable in the control group, they rose significantly in the deficient group after vitamin K injection. The question is: is there a transformation of vitamin K into menaquinone and/or is there a preferential utilization of one of the vitamin K active compounds?

Topics: Animals; Chickens; Diet; Female; Injections, Intravenous; Liver; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

Topics: Female; Hospitals, Maternity; Humans; Infant; Infant, Newborn; Japan; Male; Maternal-Child Nursing; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

A prospective study was performed in Okazaki, Japan, to attempt to establish a more effective system of prophylaxis for vitamin K deficiency in infancy (VKDI). During the first year, a Normotest (Hepaplastintest) was performed in all infants at one week and at one month of age. Two mg of vitamin K was administered orally to those whose Normotest values were below 40%. i.e., the non-prophylactic administration of vitamin K (NPVK). During the second year of the study, all newborn infants received prophylactic vitamin K (PVK) within 24 hours of birth and at one week of age. The dosage was repeated at one month of age depending on the Normotest value. A total of 7,059 infants, comprising 93.3% of the live births in the city of Okazaki, were enrolled in this study. Data from 5,431 of these infants were used in the analysis of the results. In the NPVK group, 20 of the 2,791 infants had Normotest values below 40% at one month of age while 20 of the 2,640 in the PVK group had low values despite the prophylactic administration of vitamin K. Considering the prevalence of low Normotest values (less than or equal to 40%) at one month of age and the predicted Normotest values, it was concluded that the month of birth (June-September), the age of the mother (21-29 years), the birth order (first-born) and male sex are risk factors for vitamin K deficiency in infancy.

Topics: Adult; Birth Order; Female; Hospitals, Maternity; Humans; Infant; Infant, Newborn; Japan; Male; Prevalence; Prospective Studies; Reference Values; Risk Factors; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Humans; Infant, Newborn; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Administration, Oral; Age Factors; Biliary Tract Diseases; Cerebral Hemorrhage; Ecchymosis; Female; Gastrointestinal Hemorrhage; Hemorrhage; Hemothorax; Humans; Infant; Infant, Newborn; Liver Diseases; Male; Sweden; Time Factors; Vitamin K; Vitamin K Deficiency

The cause of a fatal condition characterized by hemorrhagic cardiomyopathy, hemothorax, and coagulation defects in hysterectomy-derived male mice was investigated. Microscopic heart alterations included multifocal hemorrhage and necrosis with variable degrees of acute inflammation and fibroplasia that were most severe in the region of the atrioventricular junction. A spontaneous outbreak was arrested by increasing menadione Na-bisulfite (vitamin K) in the feed to 20 ppm. The complete syndrome including hemorrhagic cardiomyopathy was readily reproduced in germ-free male mice given a vitamin K-free diet, and in conventional male and female mice given Warfarin in the diet. We concluded that the cause of this condition was vitamin K deficiency.

Topics: Animals; Blood Coagulation Disorders; Cardiomyopathies; Female; Hemorrhagic Disorders; Hemothorax; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred CBA; Myocardium; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Administration, Oral; Adult; Breast Feeding; Fetal Blood; Humans; Infant, Newborn; Infusions, Parenteral; Injections, Intramuscular; Prospective Studies; Prothrombin; Reference Values; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Patients with extensive small-bowel resection may experience malabsorption and nutrient deficiencies. We evaluated the ability to absorb fat and fat-soluble vitamins in a short-gut patient. For 18 wk after stopping intravenous lipid, while consuming a low-lactose, low-fat diet, he exhibited no clinical manifestations of essential fatty acid deficiency (EFAD). Serum 20:4n-6 (20:4 omega-6) and 18:2n-6 fatty acid concentrations were normal, whereas the concentration of 20:3n-9 remained less than or equal to 0.1% of total serum fatty acids. Although serum vitamin A was normal, beta-carotene was undetectable despite oral supplementation. Prothrombin time was elevated until parenteral vitamin K was given. This patient has fat absorption adequate to prevent EFAD but inadequate absorption of fat-soluble vitamins. In patients with short bowel, the requirements for parenteral lipids and fat-soluble vitamins should be determined independently.

Topics: Absorption; Adult; Avitaminosis; beta Carotene; Carotenoids; Fats; Fatty Acids, Essential; Humans; Infusions, Parenteral; Lipids; Male; Prothrombin Time; Short Bowel Syndrome; Solubility; Vitamin K; Vitamin K Deficiency

Topics: Adult; Humans; Infant; Infant, Newborn; Vitamin K; Vitamin K Deficiency

Anticoagulation instability due to a change in intake of vitamin K after dietary modification was observed in 2 patients on long-term oral anticoagulants. One patient developed diffuse bruises treated conservatively with fresh frozen plasma transfusion and the other had a thrombosed aortic prosthesis which required emergency operation. To prevent such complications, dietary modification especially with food rich in vitamin K should be undertaken with care in patients on long-term oral anticoagulants.

Topics: Adult; Aortic Valve; Blood Coagulation; Diet; Drug Interactions; Female; Heart Valve Prosthesis; Humans; Male; Middle Aged; Skin Diseases; Thrombosis; Vitamin K; Vitamin K Deficiency; Warfarin

We studied the effect of vitamin K(MK-4) on the prevention of vitamin K deficiency in the early neonatal period. MK-4 (20 mg/day) was given orally for 1-7 days to 183 pregnant women at 37-39 weeks gestation. In the MK-4 treated group, there were no cases of melena neonatorum but there were 9 cases in the untreated group (9/757, 1.2%). To investigate the influence of MK-4 administration on liver function and the VK dependent coagulation system, maternal and umbilical venous blood were taken to measure T-Bil, GOT, GPT, gamma-GTP, LDH, and II, VII, X activity and HPT. There was no significant difference between these values in MK-treated and untreated groups. MK-4 concentrations were measured in the maternal and umbilical venous blood of 68 subjects. The level of MK-4 in umbilical venous blood was less than 0.1 ng/ml in 17 of 21 subjects not treated with MK-4 but it was over 0.1 ng/ml in 30 of 47 MK-4 treated subjects. However, no MK-4 was detected in 6 of 8 subjects who were treated for 1 day. The level of MK-4 in maternal blood was less than 0.1 ng/ml in 12 of 21 untreated subjects but it was 0.19-92.6 ng/ml in all of the 47 MK-4 treated subjects. The mean MK-4 concentration in cord blood as a percentage of that in maternal blood was 17.9%. These findings indicate that MK-4 is effectively transported from maternal to fetal blood through the placenta and its administration to pregnant women is useful in preventing melena neonatorum.

Topics: Administration, Oral; Blood Coagulation Factors; Female; Humans; Infant, Newborn; Liver; Maternal-Fetal Exchange; Placenta; Pregnancy; Vitamin K; Vitamin K Deficiency

Topics: Biomarkers; Blood Coagulation Factors; Hemorrhage; Humans; Infant, Newborn; Protein Precursors; Prothrombin; Vitamin K; Vitamin K Deficiency

The Committee on Infant Nutrition of the Dutch National Cross Association and the Education Bureau on Food and Nutrition, and the Dutch Paediatric Association recommend the administration of a single oral dose of 1 mg vitamin K1 at birth to all healthy infants in order to prevent haemorrhagic disease of the newborn (HDN). Parenteral administration of vitamin K1 at birth is recommended for newborn especially at risk. For infants who are wholly or largely breastfed a daily dose of 25 micrograms vitamin K1 orally is recommended for the first three months, to be increased to 50 micrograms per day in case of additional risk factors. Literature on causes of vitamin K deficiency, incidence of HDN and trends in prophylaxis is summarized and issues which require further clarification are indicated.

Topics: Bottle Feeding; Breast Feeding; Cerebral Hemorrhage; Humans; Infant; Infant Nutritional Physiological Phenomena; Infant, Newborn; Risk Factors; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

A coagulopathy attributable to a deficiency of vitamin K-dependent clotting factors (II, VII, IX, and X) was diagnosed in 3 Devon Rex cats. There was no evidence for exposure to vitamin-antagonist-related rodenticides. The cats did not have evidence of hepatic disease, gastrointestinal disease, or fat malassimilation. Oral treatment with vitamin K1 resulted in normalization of clotting factor concentrations. However, when treatment was discontinued in 2 cats, prothrombin and activated partial thromboplastin values became prolonged again, although the cats did not have clinical signs of a bleeding disorder.

Topics: Animals; Blood Coagulation Disorders; Breeding; Cat Diseases; Cats; Factor VII Deficiency; Factor X Deficiency; Female; Hemophilia B; Hypoprothrombinemias; Male; Partial Thromboplastin Time; Pedigree; Prothrombin; Prothrombin Time; Vitamin K; Vitamin K Deficiency

Cephalosporin antibiotics with N-methyl-thio-tetrazole (NMTT) side chains have been known to be associated with the development of hypoprothrombinemia. However, it has not been fully established whether these symptoms are induced by an inhibition of vitamin K production by intestinal microorganisms or by an inhibitory action of these antibiotics on endogenous vitamin K metabolism. Therefore, an attempt has been made to clarify the above-mentioned ambiguity by using germfree mice in which primary vitamin K deficiency can be established within a short experimental period. Germfree (GF) and conventional (CV) ICR male mice, 8-13 weeks old were used in this experiment. Vitamin K deficient (Def) and menaquinone-4 supplemented diet (MK-4) were fed to the mice in both rearing conditions. In the antibiotic-treated group, sodium latamoxef (LMOX, 300 mg/kg B.W./day) was intraperitoneally administered once a day, and in the control group the same volume of saline (Saline) was administered. Severe vitamin K deficient symptoms were observed in the GF-K-Def-LMOX group, and both prothrombin time (PT) and activated-partial thromboplastin time (APTT) values were prolonged on the 8th day of the experimental period compared with the GF-K-Def-Saline group. Furthermore the mortality rate of GF-K-Def-LMOX group was comparatively higher than that of the Saline group. This study has provided evidence that vitamin K deficiency is amplified by an administration of LMOX even in the absence of intestinal flora.

Topics: Animals; Anti-Bacterial Agents; Bacteroides; Blood Coagulation; Diet; Escherichia coli; Germ-Free Life; Intestinal Mucosa; Intestines; Liver; Male; Mice; Moxalactam; Partial Thromboplastin Time; Prothrombin Time; Vitamin K; Vitamin K 1; Vitamin K Deficiency

The effect of prophylaxis with oral or intramuscular vitamin K1 (Konakion) on the hypoprothrombinaemia and on the rate of detectable acarboxyprothrombin of full-term newborns was investigated. Factor II clotting activity, factor II activity by Echis carinatus venom, factor II protein concentration and acarboxyprothrombin were determined in four groups of breast-fed infants. In the untreated group and in the group where the babies received vitamin K1 orally at birth the factor, II clotting activity was decreased and the rate of acarboxyprothrombin positive cases was increased significantly (from 30% and 28% to 55% and 52% respectively) at the 3d and 5-7th days of age. By the other two groups where 1 mg vitamin K1 was given intramusculary or 2-3 mg vitamin K1 was given orally with the first milk-feed, the factor II clotting activity increased at 3d and 5-7th days of life. In these groups the rate of acarboxyprothrombin positive babies was reduced at 3d day of life from 36% and 35% (cord blood values) to 16% and 13% respectively, and there was found acarboxyprothrombin in none of the babies at 5-7th days of life. These findings support that vitamin K1 given orally at birth is ineffective to prevent vitamin K deficiency, but when it was given with the first feed orally to well, mature babies it seems to be enable to protect the early haemorrhagic disease of the newborns.

Topics: Administration, Oral; Biomarkers; Humans; Infant, Newborn; Injections, Intramuscular; Protein Precursors; Prothrombin; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Hemorrhage; Humans; Infant, Newborn; Vitamin K; Vitamin K Deficiency

Rats given a low-fibre diet based on boiled white rice developed symptoms of severe vitamin K deficiency within 23 d. Inclusion of autoclaved black-eye beans (Vigna unguiculata) in the diet prevented the bleeding syndrome. To test the hypothesis that deficiency resulted from low phylloquinone intake exacerbated by inadequate production of menaquinones by the enteric bacteria, a follow-up experiment was carried out in which groups of rats were given an all-rice diet, a rice + beans diet or a stock diet. Rats on the all-rice diet had significantly lower faecal concentrations of the main menaquinone-producing bacterial species (Bacteroides fragilis and Bacteroides vulgatus) than animals on either of the other two diets. This coupled with the much lower faecal output on this diet suggests that total menaquinone production was low for the all-rice diet. The alterations in faecal flora were associated with several significant changes in caecal metabolism. Rats given the stock diet had much shorter caecal transit times and a considerably greater proportion of butyric acid in volatile fatty acid end-products than did rats on either of the other two diets.

Topics: Animals; Bacteria; Bacteroides; Butyrates; Cecum; Diet; Fabaceae; Fatty Acids, Volatile; Feces; Gastrointestinal Transit; Male; Oryza; Plants, Medicinal; Rats; Rats, Inbred Strains; Vitamin K; Vitamin K Deficiency

Topics: Biomarkers; Gestational Age; Hemorrhage; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Milk, Human; Protein Precursors; Prothrombin; Vitamin K; Vitamin K Deficiency

Alimentary deficiency of vitamin K in rats causes a decrease in the level of in vivo occupied nuclear 1,25 (OH)2D3 receptors in small intestinal mucosa and an 2-2.5-fold increase in the ability of cytosolic 1,25 (OH)2D3-receptor complexes to bind to heterologous DNA. The 1,25 (OH)2D3 binding by the receptors is thereby unaffected. Preincubation of kidney and intestinal cytosol of rats with the secondary K-avitaminosis induced by vitamin K antagonist with the microsomal vitamin K-dependent gamma-carboxylation system sharply decreases the binding of the 1.25 (OH)2D3-receptor complexes to DNA. In rats treated with the vitamin K antagonist in combination with a low calcium diet, the subsequent maintenance on a high calcium diet does not cause, in contrast with vitamin K-repleted animals, a sharp decrease of the level of the in vivo occupied 1,25 (OH)2D3 receptors. In vitro Ca2+ cations decrease the binding of the 1,25 (OH)2D3-receptor complexes to DNA only in vitamin K-repleted rats (ED50 = 2.5 x 10(-6) M). The existence of a vitamin K-dependent Ca-sensitive mechanism regulating the binding of the 1,25 (OH)2D3 receptor to DNA has been postulated for the first time.

Topics: Animals; Cell Nucleus; Chromatography, Liquid; DNA; Intestine, Small; Kidney; Male; Rats; Rats, Inbred Strains; Receptors, Calcitriol; Receptors, Steroid; Vitamin K; Vitamin K Deficiency

We studied whether the administration of vitamin K to mothers could increase the concentration of vitamin K in breast milk and prevent idiopathic vitamin K deficient bleeding in breast-feeding infants. Sixty puerperal women were divided into three groups, the control group, Menaquinone-4 (MK-4) administered group and vitamin K1 administered group. We measured the concentrations of vitamin K1, MK-4 and MK-7 in maternal plasma and breast milk on the fourth day after delivery. In the MK-4 group, the concentrations of MK-4(2.13 ng/ml in plasma, 49.3 ng/ml in milk) were significantly higher than in the control group (0.28 ng/ml, 1.51 ng/ml). In the vitamin K1 group, the concentrations of vitamin K1 (49.0 ng/ml in plasma, 71.6 ng/ml in milk) were significantly higher than in the control group (1.17 ng/ml, 2.41 ng/ml). The concentration rates (milk/plasma ratio) of vitamin K1, MK-4 and MK-7 were 2.52, 5.43 and 0.52 in the control group, 1.60, 40.2 and 0.67 in the MK-4 group and 1.65, 10.8 and 0.71 in the vitamin K1 group, respectively. The concentration rate of MK-4 was higher than that of vitamin K1 and was increased by MK-4 administration. After delivery, the daily concentration of MK-4 in milk was increased from 1.69 ng/ml on the first day to 49.3 ng/ml on the fourth day in the MK-4 group. These results indicate that MK-4 is accumulated and concentrated into breast milk, and continuous MK-4 administration can increase the concentration of vitamin K in milk, preventing idiopathic vitamin K deficient bleeding in infants.

Topics: Female; Humans; Infant; Milk, Human; Postpartum Period; Pregnancy; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

Topics: Chromatography, High Pressure Liquid; Female; Humans; Infant, Newborn; Male; Reference Values; Spectrometry, Fluorescence; Vitamin K; Vitamin K Deficiency

Topics: Humans; Infant, Newborn; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

The vitamin K-dependent carboxylation of the prothrombin precursor PIVKA II (protein induced by vitamin K absence analogous to Factor II) is essential for the synthesis of prothrombin. The noncarboxylated precursor is found in peripheral blood in the presence of vitamin K deficiency. In this study prothrombin time, Factor II and Factor VII activity, and PIVKA II were investigated in 57 newborns without vitamin K prophylaxis in order to assess their vitamin K status. Two-dimensional immunoelectrophoresis demonstrated the presence of PIVKA II in 21% of the newborns, predominantly on the second day. The PIVKA-II positive group showed significantly lower prothrombin times than the PIVKA II-negative group. An oral dose of 3 mg vitamin K (Konakion) was administered to 35 healthy newborns in a second group with the first feeding. On the second day of life, these infants showed significantly higher vitamin K-dependent laboratory parameters than the group not given vitamin K; only 9% of the treated infants were positive for PIVKA II.

Topics: Biomarkers; Factor VII; Hemostasis; Humans; Infant, Newborn; Protein Precursors; Prothrombin; Prothrombin Time; Reference Values; Vitamin K; Vitamin K Deficiency

Topics: Hemorrhage; Humans; Infant, Newborn; Vitamin K; Vitamin K Deficiency

Topics: Hemorrhage; Humans; Infant, Newborn; Risk Factors; Vitamin K; Vitamin K Deficiency

We measured plasma vitamin K concentrations in 194 5-day-old infants three hours after administration of a 4-mg dose of vitamin K (menaquinone-4, Kaytwo syrup, Eisai Co Ltd, Tokyo, Japan). We investigated association with other factors contributing to vitamin K deficiency. These plasma vitamin K concentrations varied greatly among the neonates from values below the limit of detection (2 ng/mL) to more than 1000 ng/mL. The vitamin K concentration was associated with nutritive vitamin K deficiency represented by plasma protein induced by vitamin K absence or antagonist-II (PIVKA-II) values. The wide variation in vitamin K absorption is considered to be one of the major causative factors in infantile vitamin K deficiency.

Topics: Administration, Oral; Bile Acids and Salts; Female; Humans; Infant, Newborn; Male; Milk, Human; Time Factors; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Vitamin K status was evaluated by measuring blood acarboxyprothrombin (PIVKA-II) levels on the fifth day of life. The incidence of PIVKA-II-positive infants was higher in breast-fed babies than in those given supplementary (mixed) feeding. The median of total amount of milk intake during the first 3 days was significantly lower in PIVKA-II-positive infants than in PIVKA-II-negative infants among infants given both types of feedings. In addition, there was a significant negative correlation between a positive PIVKA-II proportion and the amount of milk intake in the breast-fed babies. The minimum dose of vitamin K2 necessary to prevent a positive PIVKA-II reading was 15 micrograms among babies with a normal absorption potential.

Topics: Animals; Biomarkers; Breast Feeding; Dose-Response Relationship, Drug; Food, Fortified; Humans; Infant Food; Infant, Newborn; Milk; Protein Precursors; Prothrombin; Vitamin K; Vitamin K Deficiency

Oxacephem antibiotics have been developed to increase the antibacterial activity of cephem antibiotics, but the effect of 1-oxygen replacement of cephem antibiotics on blood coagulation activities is not yet known. Therefore, latamoxef (LMOX), flomoxef (FMOX) and their 1-S congeners were examined for their effects on prothrombin time, activated partial thromboplastin time, plasma prothrombin and Factor VII levels, plasma and liver descarboxyprothrombin (PIVKA-II) levels, and liver microsomal vitamin K epoxide reductase activities in rats kept on a vitamin K-deficient diet. Under the vitamin-deficient states, LMOX, FMOX and their 1-S congeners inhibited the vitamin K epoxide reductase, although the effect of FMOX or its congener was much less than that of LMOX, and they decreased the blood clotting activities in rats fed a vitamin K-deficient diet. However, no difference was found in these effects between LMOX and its 1-S congener or between FMOX and its 1-S congener. This result suggests that the 1-oxygen replacement of cephem antibiotics is not responsible for the hypoprothrombinemic effect of the antibiotics.

Topics: Animals; Blood Coagulation; Cephalosporins; Factor VII; Fibrinogen; Male; Moxalactam; Partial Thromboplastin Time; Platelet Aggregation; Prothrombin Time; Rats; Rats, Inbred Strains; Vitamin K; Vitamin K Deficiency

Topics: Gastrointestinal Hemorrhage; Humans; Infant Nutritional Physiological Phenomena; Infant, Newborn; Milk, Human; Quinones; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

The paper describes 8 cases of delayed haemorrhagic disease caused by vitamin K deficiency, occurring from 16 days to 3 months after birth and observed in 1982-87. All these infants were breast fed and had received no vitamin K prophylaxis. On the basis of these findings, the preventive role of vitamin K in breast fed infants is emphasised.

Topics: Age Factors; Breast Feeding; Cerebral Hemorrhage; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Infant; Infant, Newborn; Male; Vitamin K; Vitamin K Deficiency

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Biomarkers; Humans; Kinetics; Protein Precursors; Prothrombin; Prothrombin Time; Vitamin K; Vitamin K Deficiency

Vitamin K deficiency in rats caused a rise of in vivo occupied 1,25(OH)2D3 receptor level in chromatin of the intestinal mucosa and a marked (2-2.5-fold) increase of intestinal cytosolic 1,25(OH)2D3-receptor complex binding with heterologous DNA, whereas maximum binding capacity and equilibrium dissociation constant of cytosolic 1,25 (OH)2D3 receptors did not change. Preincubation of renal and intestinal cytosol of vitamin K-deficient rats with microsomal vitamin K-dependent gamma-carboxylating system reduced sharply 1,25(OH)2D3-receptor complex binding with DNA. In rats treated by vitamin K antagonist along with a low calcium diet, no dramatic decrease of occupied 1,25(OH)2D3 receptors occurred after the animals were maintained with a high calcium diet. No such effect was observed in vitamin K-replete rats. The data demonstrate vitamin K-dependent Ca-sensitive qualitative modification of 1,25(OH)2D3 receptor dropping its binding performance to DNA.

Topics: 4-Hydroxycoumarins; Animals; Calcitriol; Calcium, Dietary; Cellulose; DNA; Drug Interactions; Male; Rats; Rats, Inbred Strains; Receptors, Calcitriol; Receptors, Steroid; Vitamin K; Vitamin K Deficiency

Topics: Adult; Aged; Biomarkers; Biomarkers, Tumor; Carcinoma, Hepatocellular; Half-Life; Humans; Liver Neoplasms; Middle Aged; Protein Precursors; Prothrombin; Vitamin K; Vitamin K Deficiency

Topics: Blood Coagulation Factors; Factor VII; Factor X; Female; Fetal Blood; Humans; Infant, Newborn; Maternal-Fetal Exchange; Pregnancy; Prothrombin; Vitamin K; Vitamin K Deficiency

Feeding of a vitamin K-deficient diet caused the development of hypoprothrombinemic changes in rats such as prolongation of prothrombin time (PT) and activated partial thromboplastin time (APTT), decreases in plasma prothrombin and clotting factor VII levels, and an increase in the descarboxyprothrombin (PIVKA) level in both plasma and liver. Successive administrations of latamoxef (LMOX) to the vitamin K-deficient rats resulted in the further enhancement of these changes. After the development of hypoprothrombinemia with LMOX, a single subcutaneous injection of vitamin K1 normalized most of these abnormalities in blood coagulation parameters within 6 hr. When vitamin K was given at 200 micrograms/kg, PT, APTT and the plasma PIVKA level showed normal values for at least 8 days even when the animals were fed a vitamin K-deficient diet and treated with LMOX during the recovery period. The amount of vitamin K required to maintain most of the blood coagulation parameters in the normal range was about 3 micrograms/kg/day. The plasma level of vitamin K was higher than 0.3-0.5 ng/ml when the blood coagulation parameters were maintained in the normal range.

Topics: Animals; Blood Coagulation Tests; Female; Hypoprothrombinemias; Moxalactam; Rats; Rats, Inbred Strains; Vitamin K; Vitamin K Deficiency

Three one month old infants with idiopathic late haemorrhagic disease due to vitamin K deficiency are reported. Patients had been exclusively breast fed and had not received vitamin K at birth. Initial symptomatology was typical in the three cases. Two of them had an intracranial haemorrhage with exitus in one of them. Coagulation study showed non measurable levels of PT and PTT and a significant reduction in vitamin K dependent factors. Coagulopathy was corrected with parenteral administration of vitamin K and fresh plasma. Pathogenic factors of this entity are reviewed and present day recommendations to prevent occurrence of this problem are discussed.

Topics: Female; Humans; Infant; Infant, Newborn; Male; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

On the basis of an inquiry held in Switzerland in May 1988, over 99% of all newborn receive vitamin K prophylaxis, 59% orally and 41% intramuscularly. In the previous 2 1/2 years, ten cases of bleeding due to vitamin K deficiency had been observed, of which two were inadequately documented. In two children there was early haemorrhage and late haemorrhage in eight. The latter were all exclusively breast-fed and had received oral vitamin K prophylaxis. Seven presented with vitamin K deficiency due to cholestasis or chronic diarrhea. The only "idiopathic" case is insufficiently documented. The advantages and disadvantages of oral and intramuscular prophylaxis are discussed. A definite stand in favour of the one route or the other is not possible at present. However, the continuation of general prophylaxis is undoubtedly necessary.

Topics: Female; Hemorrhage; Humans; Infant; Infant, Newborn; Male; Switzerland; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

The modulation of phosphosphingolipid synthesis by vitamin K depletion has been observed in the vitamin K-dependent microorganism, Bacteriodes levii. When cultured briefly without the vitamin, a reduction occurred in the activity of the first enzyme of the sphingolipid pathway, 3-ketodihydrosphingosine synthase. In this report, 16-day-old mice were treated with the vitamin K antagonist, warfarin. Brain microsomes from these animals showed a 19% reduction in synthase activity. Mice treated with warfarin for 2 weeks showed a major reduction in sulfatide level (42%), with a lesser degree or no reduction in levels of gangliosides and cerebrosides. In further experiments, mice were treated with warfarin for 2 weeks and a group was then injected with vitamin K1 (aquamephyton) for 3 days. Enzyme activity returned to a normal level within 2-3 days. Sulfatide levels had increased 33% in the vitamin K-injected group and ganglioside levels also increased, where levels of cerebrosides and sphingomyelin declined. Sulfatide synthesis determined by [35S] sulfate incorporation, showed a 52% increase in incorporation following administration of vitamin K for 3 days. These results suggest a role for vitamin K in the biosynthesis of sulfatides and other sphingolipids in brain. This putative role could be by post-translational protein modification analogous to the role of vitamin K in other systems.

Topics: Animals; Brain; Glycosphingolipids; Mice; Mice, Inbred ICR; Oxo-Acid-Lyases; Phospholipids; Sphingolipids; Sulfoglycosphingolipids; Vitamin K; Vitamin K Deficiency; Warfarin

Osteocalcin (a vitamin K-dependent, bone-specific protein) is widely accepted as a marker of osteoblastic activity. The present study was conducted to determine if a vitamin K deficiency would affect fracture healing by virtue of an alteration in osteocalcin metabolism. Thirty male Sprague-Dawley rats were divided into two groups. The control group was fed a diet that was lacking in, but offered water replete with vitamin K. The experimental group was fed a vitamin K-deficient diet and was offered water that was lacking in vitamin K. After two weeks, vitamin K deficiency was established in the experimental group as shown by decreased urinary excretion of gamma-carboxyglutamic acid and an elevation of serum prothrombin times to between two to two and one-half times the control values. At this time, a standard, closed femoral fracture was produced. Six weeks later, the animals were killed. The bones were biomechanically tested in torsion. Subsequent to mechanical testing, the calluses were retrieved, and the osteocalcin content and the degree of gamma carboxylation of the osteocalcin in the calluses were measured. The results show that despite significant alterations in the gamma carboxylation of osteocalcin and elevation of prothrombin times to two to two and one-half times the control values, there were no differences in the mechanical properties of the calluses. Furthermore, there were no differences in the content or gamma carboxylation of osteocalcin in these calluses. Apparently, in vitamin K deficiency, fracture callus achieves normal mechanical properties and may have a mechanism for the gamma carboxylation of glutamic acids in osteocalcin despite a substantial depression of this activity in the rest of the body.

Topics: 1-Carboxyglutamic Acid; Animals; Bony Callus; Calcium-Binding Proteins; Femoral Fractures; Male; Osteocalcin; Prothrombin Time; Rats; Rats, Inbred Strains; Vitamin K; Vitamin K Deficiency; Wound Healing

Topics: Administration, Oral; Blood Coagulation Tests; Humans; Infant, Newborn; Vitamin K; Vitamin K Deficiency

Topics: Breast Feeding; Cerebral Hemorrhage; Humans; Infant; Infant, Newborn; Vitamin K; Vitamin K Deficiency

The in vivo effects of heterocyclic thiol compounds, corresponding to the 3'-position substituents of several beta-lactam antibiotics, on blood coagulation factors and on liver microsomal gamma-glutamylcarboxylation (gamma-carboxylation) activity were evaluated in rats maintained on a vitamin K-deficient diet. These rats, when compared to normal control animals, exhibited hypoprothrombinemic changes: prolongation of both prothrombin time and activated partial thromboplastin time, decreases in factor VII and plasma prothrombin, and increases in PIVKA II (descarboxyprothrombin) both in plasma and liver. They also displayed a marked increase in liver microsomal gamma-carboxylation activity. These blood coagulation variables could be altered markedly by administering various heterocyclic thiol compounds to the vitamin K-deficient rats, although these compounds did not inhibit gamma-carboxylation activity in an assay system using phylloquinone. A similar pattern of alteration was observed when some beta-lactam antibiotics were administered. Increased microsomal gamma-carboxylation activity in antibiotic-treated vitamin K-deficient rats was normalized by the administration of vitamin K, concomitant with the recovery of blood coagulation variables to the normal range. The results indicate that antibiotic-induced hypoprothrombinemia in vivo is not caused by inhibition of enzymes of the gamma-carboxylation system, such as vitamin K reductase and gamma-glutamylcarboxylase, but is related to the endogenous vitamin K level.

Topics: Animals; Anti-Bacterial Agents; beta-Lactams; Blood Coagulation Factors; Carbon-Carbon Ligases; Hypoprothrombinemias; Ligases; Rats; Rats, Inbred Strains; Sex Factors; Sulfhydryl Compounds; Vitamin K; Vitamin K Deficiency

Male and female rats were fed an ordinary diet which contained about 500 ng vitamin K/g or a vitamin K-deficient diet containing less than 5 ng vitamin K/g. Hypoprothrombinemic changes such as prolongation of the prothrombin time (PT) and activated partial thromboplastin time (APTT) were detected in male rats within 4-6 days after feeding of the vitamin K deficient diet. Blood clotting factor VII and descarboxy prothrombin (PIVKA) levels changed rapidly, with maximum alteration at 2-4 days. Similar changes in factor VII and PIVKA levels were observed in female rats, but they appeared only after feeding of the K deficient diet for a long period. PT and APTT in female rats showed slight or no alteration even after 10 day feeding of the K-deficient diet. These results indicate that male rats are more susceptible to vitamin K deficiency than female rats. Administration of latamoxef led to a dose-dependent development of hypoprothrombinemia in vitamin K-deficient female rats. The hypoprothrombinemia in vitamin K-deficient female rats was caused by beta-lactam antibiotics with N-methyltetrazolethiol, thiadiazolethiol and methyl-thiadiazolethiol as the 3'-position substituent of the cephem nucleus.

Topics: Animals; Anti-Bacterial Agents; beta-Lactams; Blood Coagulation; Factor VII; Female; Hypoprothrombinemias; Male; Partial Thromboplastin Time; Prothrombin Time; Rats; Rats, Inbred Strains; Sex Factors; Vitamin K; Vitamin K Deficiency

The mechanism of induction of vitamin K (VK) deficiency in newborn babies and antibiotics-treated patients has not entirely been clarified because of the difficulty in preparing the true VK deficient model-animals and the complication in an assay system for VK derivatives and of their metabolites until now. Germfree animal is thought to be an useful tool to establish a primary VK deficiency not caused by VK antagonists etc., because of the lack of their intestinal flora. Germfree (GF) and conventional (CV) ICR/JCL male mice, 12-13 week-old were used in this experiment. VK deficient (K-Def), menaquinone-4 (MK-4) supplemented (MK-4), and VK3 (menadione) supplemented diet (K3) were fed to the mice in both GF and CV states. After 8 days, severe VK deficient symptoms were occurred only in GF-K-Def group, whereas not at all in CV-K-Def group. Both prothrombin time (PT) and activated partial thromboplastin time (APTT) were also prolonged only in GF-K-Def group. From the HPLC analysis of MK-4 content in liver, it was suspected that the content of MK-4 which has been thought to be an active form of VK was not necessarily paralleled with the degree of VK deficiency.

Topics: Animals; Body Weight; Disease Models, Animal; Germ-Free Life; Hemorrhage; Liver; Male; Mice; Mice, Inbred ICR; Organ Size; Partial Thromboplastin Time; Prothrombin Time; Vitamin K; Vitamin K Deficiency

A case of malabsorption of vitamin K, leading to a vitamin K-dependent clotting factor deficiency that developed during the eighth gestational month, is reported. Evaluation of the coagulopathy at term showed the cause to be an obstructive hepatobiliary disorder. Given the pathophysiologic relationship between the coagulation cascade and the hepatic and biliary systems, routine measurement of the prothrombin and partial thromboplastin times is advised for all patients with evidence of hepatobiliary dysfunction.

Topics: Adult; Blood Coagulation Disorders; Cholestasis; Female; Humans; Pregnancy; Pregnancy Complications, Hematologic; Vitamin K; Vitamin K Deficiency

Throughout Japan a total of 543 cases of vitamin K deficiency occurring in infants over 2 weeks of age were reported from January 1981 to June 1985. Of these cases, 427 showed no obvious reasons for vitamin K deficiency; this sort of case is known as "idiopathic vitamin K deficiency in infancy". Another 57 cases had bleeding episodes due to vitamin K deficiency associated with obvious hepatobiliary lesions, chronic diarrhoea, long-term antibiotic therapy, etc; this sort is called "secondary vitamin K deficiency in infancy". The third group, consisting of 59 cases, was made up of the so-called "near miss" type, in which a haemorrhagic tendency, without any obvious clinical haemorrhage, was discovered by Normotest, at the time of mass screening in most cases. In the idiopathic group, 269 cases (63.0%) developed bleeding episodes between the 1st and 2nd months of age, and 387 cases (90.0%) were entirely breast-fed. Intracranial haemorrhage was observed in 353 cases (82.7%) of this group. Moreover, slight elevation of serum transaminase and direct type bilirubin levels were observed in the idiopathic group. Liver dysfunction of unknown origin may play some role in the onset of vitamin K deficiency in infancy.

Topics: Alanine Transaminase; Aspartate Aminotransferases; Bilirubin; Breast Feeding; Female; Humans; Infant; Infant, Newborn; Japan; Male; Seasons; Sex Factors; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Humans; Infant; Infant, Newborn; Vitamin K; Vitamin K Deficiency

Topics: Adult; Aged; Humans; Middle Aged; Prothrombin Time; Rifampin; Vitamin K; Vitamin K Deficiency

Topics: Humans; Hypoprothrombinemias; Infant; Infant, Newborn; Milk, Human; Syndrome; Vitamin K; Vitamin K 1; Vitamin K Deficiency

We have evaluated a boy who had excessive bleeding and bruising from birth and showed markedly prolonged prothrombin times, partially correctable by oral vitamin K administration. Additional laboratory studies demonstrated decreased activities of plasma factors II, VII, IX, and X; near normal levels of immunologically detected and calcium binding-independent prothrombin; undercarboxylation of prothrombin; excess circulating vitamin K epoxide; decreased excretion of carboxylated glutamic acid residues; and abnormal circulating osteocalcin. These results all are consistent with effects resulting from decreased posttranslational carboxylation secondary to an inborn deficiency of vitamin K epoxide reductase. This individual also had nasal hypoplasia, distal digital hypoplasia, and epiphyseal stippling on infant radiographs, all of which are virtually identical to features seen secondary to first-trimester exposure to coumarin derivatives. Therefore, by inference, the warfarin embryopathy is probably secondary to warfarin's primary pharmacologic effect (interference with vitamin K-dependent posttranslational carboxylation of glutamyl residues of various proteins) and may result from undercarboxylation of osteocalcin or other vitamin K-dependent bone proteins.

Topics: 1-Carboxyglutamic Acid; Abnormalities, Drug-Induced; Calcium-Binding Proteins; Child; Chromatography, High Pressure Liquid; Female; Fetal Diseases; Fingers; Humans; Male; Nose; Osteocalcin; Phenotype; Pregnancy; Prothrombin; Radiography; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Warfarin

Mouse Lewis lung (LL) carcinoma cells possess a factor X activator (procoagulant) that is inhibited in vivo by warfarin treatment or diet-induced vitamin K deficiency. This inhibition suggests that vitamin-K-dependent proteins are involved in LL cell activation of factor X. A LL primary tumor clone (LL13) was isolated which contained a warfarin-sensitive vitamin-K cycle of metabolism and expressed factor X procoagulant activity. LL13 cells exposed to media containing warfarin or deficient in vitamin K grew as well as cells in normal media, and activated factor X to similar extents. In contrast, administration of warfarin to mice bearing LL13 cells inhibited factor X procoagulant activity as well as the vitamin K cycle of metabolism in the primary tumors. In relation to LL13 cells grown in media containing fetal bovine serum, those incubated for 20 hr in media containing mouse serum or the sera from LL13-bearing mice exhibited 9- to 10-times higher levels of factor X procoagulant activity. However, LL13 cells exposed to media containing the sera of warfarin-treated LL-13-bearing mice or to barium-sulfate-adsorbed normal mouse serum activated factor X much less efficiently. Collectively, these data suggest that inhibition of vitamin K function in LL cells does not affect the extent of factor X activation and thus the intrinsic factor X procoagulant is not a vitamin-K-dependent protein. They further suggest that both a warfarin-sensitive (vitamin-K-dependent) protein present in normal mouse serum and a LL13 cell component participate in factor X procoagulant activity.

Topics: Animals; Biotransformation; Blood Coagulation Factors; Cell Line; Culture Media; Factor X; Lung Neoplasms; Male; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Breast Feeding; Female; Hemorrhage; Humans; Infant, Newborn; Vitamin K; Vitamin K Deficiency

Acarboxyprothrombin (protein induced by vitamin K absence or antagonist-II (PIVKA-II] concentrations in dried blood spots were determined in 19,029 infants at about 1 month of age as an indicator of vitamin K deficiency. We observed 51 cases with raised blood concentrations of PIVKA-II (greater than 4 AU/ml), nine of whom showed very high concentrations (greater than 20 AU/ml). For infants who did not receive vitamin K prophylaxis at birth, the incidence of the PIVKA-II test yielding positive results was significantly higher in those solely breast fed (0.51%) compared with those fed formula milk (0.18%). Among solely breast fed infants, the incidence of a very high result of the PIVKA-II test was 0.14% in those who had not received vitamin K prophylaxis at birth, 0.04% in those who received 2 mg orally, and 0.03% in those who received 2 mg orally plus a further dose of 2-4 mg orally at 7 days. Thus vitamin K prophylaxis at birth did not completely prevent vitamin K deficiency at 1 month. We administered vitamin K therapeutically to all infants whose PIVKA-II test yielded a positive result at 1 month. Only one infant with a positive result developed late neonatal intracranial haemorrhage.

Topics: Biomarkers; Female; Humans; Infant; Infant, Newborn; Male; Protein Precursors; Prothrombin; Vitamin K; Vitamin K Deficiency

4 infants (2 males, 2 females) with acute bleedings due to vitamin K-deficiency beyond the neonatal period are reported. Two infants had intracranial haemorrhage and died. All infants were born appropriate for date and became no vitamin K-prophylaxis. All were breast-fed. This report is a further prove for the existence of the late onset haemorrhagic disease of the newborn. The importance of general vitamin K-prophylaxis is outlined.

Topics: Blood Coagulation Tests; Breast Feeding; Cerebral Hemorrhage; Female; Hemorrhage; Humans; Infant; Infant, Newborn; Male; Vitamin K; Vitamin K Deficiency

Topics: Humans; Infant, Newborn; Prothrombin Time; Vitamin K; Vitamin K Deficiency

A coagulopathy due to vitamin K deficiency was discovered in 42 hospitalized patients, most of whom had been misdiagnosed as having disseminated intravascular coagulation. Factors contributing to vitamin deficiency included inadequate diet, malabsorption, failure of physicians to prescribe vitamin K supplements, antibiotic therapy, renal insufficiency, hepatic dysfunction, recent major surgery, and possibly pregnancy. Sixteen patients (34%) bled sufficiently to need red blood cell transfusions and ten patients (24%) ultimately died. Of 18 patients who also had thrombocytopenia, three did have disseminated intravascular coagulation. The deficiency, a contributor to morbidity and mortality, can be prevented by prophylactic administration of vitamin K to severely ill patients who are eating inadequately and receiving antibiotics.

Topics: Adolescent; Adult; Aged; Blood Coagulation Disorders; Blood Coagulation Tests; Critical Care; Female; Hemorrhage; Humans; Male; Middle Aged; Prospective Studies; Vitamin K; Vitamin K Deficiency

To determine the most effective way of preventing intracranial hemorrhage due to vitamin K deficiency in infants, we first performed a comparative study using Normotest on the effects of several regimens for the oral administration of vitamin K2. Based on the results, we gave vitamin K2 orally, 2 mg, at birth, and then, 4 mg, at 1 week of age (on discharge from the newborn nursery) to all infants except premature and low-birth-weight infants born in Nagasaki Prefecture, Japan. Since then, as the number of infants with vitamin K2 prophylaxis increased, patients with intracranial hemorrhage due to vitamin K deficiency decreased in number, and no patient was found in 1984. The incidence of this disease in infants with vitamin K prophylaxis was 1/68,500, which was one-twentieth of that (1/3,500 live births) before the period when most neonates received vitamin K prophylaxis. From the results, we concluded that the oral administration of vitamin K2 at birth and 1 week of age prevents this disease.

Topics: Administration, Oral; Breast Feeding; Cerebral Hemorrhage; Humans; Infant, Newborn; Vitamin K; Vitamin K Deficiency

Using a sensitive electrochemical assay for vitamin K1 and standardized techniques for breast-milk collection, we studied the vitamin K1 content of human milk during the first 5 wk of lactation with respect to 1) individual and interindividual differences, 2) the relationship of vitamin K1 to other lipids, and 3) the influence of oral supplements of vitamin K1 on breast milk concentrations. Comparison of fore and hind milk from the mothers revealed higher vitamin K1 concentrations in hindmilks, suggesting that the lipid content influences the vitamin K1 concentration in maternal milk. Samples of maternal milk from nine mothers collected from day 1 to day 36 of lactation showed significantly higher vitamin K1 concentrations in colostral milk than in mature milk. For colostral milk there was a significant correlation of vitamin K1 to cholesterol (r = 0.62) but not to total lipid or phospholipid suggesting a role for cholesterol in the secretion of vitamin K1 into colostral milk. For mature milk correlation coefficients of vitamin K1 with all lipids were low (r = 0.29-0.37) suggesting that at later stages of lactation dietary fluctuations of vitamin K1 may be a more important determinant of the vitamin K1 content of breast milk than the lipid composition. To test the influence of diet, mothers were given oral supplements of vitamin K1.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Cholesterol; Chromatography, High Pressure Liquid; Colostrum; Dose-Response Relationship, Drug; Female; Humans; Infant, Newborn; Lactation; Lipid Metabolism; Milk, Human; Phospholipids; Pregnancy; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Humans; Infant, Newborn; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Two patients with low random serum vitamin K1 concentrations but with normal prothrombin times and normal biological assays of the vitamin K dependent coagulation proteins were treated with an N-methyl-thiotetrazole cephalosporin (cefotetan) postoperatively. Four to six days later both patients developed a prolonged prothrombin time and a noticeable and specific lowering of the clotting activities of factors II, VII, IX and X, though the serum vitamin K1 concentrations remained unchanged. Crossed immunoelectrophoresis of prothrombin showed the appearance of a second peak corresponding to descarboxyprothrombin (PIVKA II). These abnormalities corrected after vitamin K administration. These data are consistent with the hypothesis that cephalosporins with an N-methyl-thiotetrazole side chain inhibit the hepatic utilisation of vitamin K but that this only causes hypoprothrombinaemia when liver reserves of vitamin K are low.

Topics: Aged; Aged, 80 and over; Blood Coagulation Factors; Cefotetan; Cephamycins; Female; Hemostasis; Humans; Immunoelectrophoresis, Two-Dimensional; Male; Postoperative Care; Prothrombin Time; Vitamin K; Vitamin K Deficiency

Topics: Blood Coagulation Tests; Blood Transfusion; Gastrointestinal Hemorrhage; Humans; Infant; Lymphangiectasis, Intestinal; Malabsorption Syndromes; Male; Protein-Losing Enteropathies; Shock, Hemorrhagic; Vitamin K; Vitamin K Deficiency

Twenty male alcoholic subjects were studied initially within 1 day after stopping alcohol and again after about 1 week. Vitamin and mineral measurements were made on blood and abnormal prothrombin molecules quantitated for vitamin K status. Nine of the 20 patients received menadiol after the initial blood sample. Twelve of the alcoholics had significant elevations of abnormal prothrombin. Of these 12, all five who received vitamin K reduced the abnormal prothrombin levels toward normal but no change was observed in the seven who did not receive vitamin K. All nine patients receiving vitamin K lowered the abnormal prothrombin level significantly whereas there was no change in those 11 who did not receive vitamin K. The prothrombin time by the one-stage technique was normal in all patients. These data suggest that the production of abnormal prothrombin is frequently present in alcoholics and this may represent a subclinical vitamin K deficiency.

Topics: Adult; Alcoholism; Humans; Male; Middle Aged; Prothrombin; Vitamin K; Vitamin K Deficiency

Topics: Blood Coagulation; Humans; Infant; Infant, Newborn; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

The effect of vitamin K(V.K) administration to the mother on the value of the Hepaplastin test (HPT) was studied in 1,000 neonates. The mean value for HPT on 4th day in the breast feeding group (BF) was 42.2%, which was significantly lower than that in the breast formula feeding group (BFF). 1.6% of BF, and 0.5% of BFF showed an HPT value below 20%. Administration of V.K2 to the mother resulted in a significant increase in the HPT value (BF; 58.9%, BFF; 59.1%). None of the cases showed a HPT value below 20% after the V.K administration. 203 neonates who showed a HPT value below 40% were treated with daily doses of 4 mg V.K2. The HPT value improved to over 40% in all cases within 3 days. V.K1 and K2 concentrations in maternal serum and milk were measured by the method using high performance liquid chromatography. Mean concentrations of V.K1 and K2 on the 4th postpartum day in serum were 0.7 and 0.4 ng/ml and those in the milk were 1.4 and 0.9 ng/ml, respectively. V.K1 administration to the mother after delivery significantly increased V.K1 in serum. V.K2 administration also increased serum V.K2 levels. When V.K1 was given to the mother, both V.K1 and K2 levels in the milk increased. Administration of V.K2 resulted only in an increase in V.K2 in the milk. These results indicated that the administration of V.K to the mother improves the HPT value of the neonate and may be useful in preventing V.K deficiency in the neonate.

Topics: Female; Humans; Infant, Newborn; Mass Screening; Milk, Human; Postpartum Period; Pregnancy; Vitamin K; Vitamin K Deficiency

Topics: Breast Feeding; Female; Humans; Hypoprothrombinemias; Infant; Vitamin K; Vitamin K Deficiency

The prevalence of vitamin K deficiency in newborn infants and the influence of perinatal risk factors were studied prospectively in 934 infants. A noncarboxylated prothrombin assay to detect proteins induced in vitamin K absence (PIVKA-II) was used to determine the presence of vitamin K deficiency; of 934 cord blood samples assayed, 2.9% were positive for PIVKA-II (0.015 to 0.15 U/ml). All infants found to have detectable PIVKA-II were born at term. The number of infants positive for PIVKA-II was greater in the group small for gestational age (7.4%) than in those appropriate (2.7%) or large (3.1%) for gestational age. Nine categories of perinatal risk groups were defined: however, the majority of infants who were PIVKA-II positive (63%) were normal. All infants received prophylactic vitamin K, and no infant with PIVKA-II in the cord sample subsequently had clinical bleeding. In two patients the rate of 50% disappearance of PIVKA-II after vitamin K administration approximated 70 hours. Two PIVKA-II positive patients with active bleeding or disseminated intravascular coagulation had an accelerated disappearance of 20 to 40 hours. The long disappearance time of PIVKA-II in a steady state may allow detection of vitamin K deficiency despite administration of vitamin K. The majority of cases of neonatal vitamin K deficiency occurred in normal newborn infants. Therefore, all infants should receive prophylactic vitamin K at birth.

Topics: Biomarkers; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Infant, Small for Gestational Age; Prospective Studies; Protein Precursors; Prothrombin; Risk; Vitamin K; Vitamin K Deficiency

Discussion about vitamin K prophylaxis has again become a matter of major concern since cases of life threatening bleeding due to late onset vitamin K deficiency have been observed in Germany. This review tries to summarize present knowledge about the clinical presentation, pathogenesis and the potential prevention of vitamin K deficiency caused bleeding in the neonatal period and infancy.

Topics: Blood Coagulation Factors; Breast Feeding; Humans; Infant; Infant, Newborn; Nutritional Requirements; Prothrombin; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Adolescent; Blood Coagulation Disorders; Child, Preschool; Female; Humans; Malabsorption Syndromes; Vitamin K; Vitamin K Deficiency

Vitamin K in oral drops and intramuscular injection given at birth to Thai infants were compared to determine whether these routes and doses would influence prothrombin complex activity, mortality or morbidity at 0.5, 1 and 2 months of age. The infants were 321 normal fullterm babies born at Bangkok Adventist Hospital in 1983, exclusively breastfed during the study. Prothrombin complex (PC) was measured by the Owren capillary thrombotest method using a reagent from Nyegaard Co., Oslo. Vitamin K was given in single 1 or 2 mg oral doses, or 1 mg im, within 12 hours of delivery. Judging by the number of PC deficient children, the 1 mg im and 2 mg oral doses of vitamin K maintained clotting factors best at 2 months of age. All formulations were significantly better than no treatment at 1 month at age. No toxicity or side effects were seen. Vitamin K deficiency is a known cause of bleeding disorders, particularly fatal and handicapping intracranial hemorrhage in newborns, in developing countries where injections cannot be given by midwives. These inexpensive oral pediatric drops may provide a practical form of primary health care for routine vitamin K prophylaxis in newborns.

Topics: Administration, Oral; Humans; Infant; Infant, Newborn; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Dose-Response Relationship, Drug; Humans; Infant, Newborn; Vitamin K; Vitamin K Deficiency

Topics: Biomarkers; Blood Coagulation Disorders; Blood Coagulation Factors; Cerebral Hemorrhage; Humans; Infant; Infant, Newborn; Male; Protein Precursors; Prothrombin; Vitamin K; Vitamin K Deficiency

Topics: Adolescent; Adult; Anti-Bacterial Agents; Female; Hemorrhage; Humans; Male; Middle Aged; Vitamin K; Vitamin K Deficiency

Topics: Blood Coagulation; Breast Feeding; Hemorrhage; Humans; Infant, Newborn; Infant, Premature, Diseases; Vitamin K; Vitamin K Deficiency

Topics: Dental Implantation; Hemostasis; Humans; Vitamin K; Vitamin K Deficiency

Topics: Cerebral Hemorrhage; Female; Humans; Infant; Ultrasonography; Vitamin K; Vitamin K Deficiency

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Avitaminosis; Folic Acid; Folic Acid Deficiency; Humans; Pyridoxine; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Deficiency; Vitamin D; Vitamin D Deficiency; Vitamin E; Vitamin E Deficiency; Vitamin K; Vitamin K Deficiency; Vitamins

The components of the factor VIII complex were estimated by immuno- and bioassays in 85 patients with liver disease. The plasma concentrations of the antigens were elevated in 65% (VIII:CAg) and in 76% (VIIIR:Ag) of patients while the biological activities were elevated in only 14% (VIII:C) and 15% (VIII:RiCof). There was no correlation with C-reactive protein, used as a measure of an acute phase reaction (X2 = 0.7; P = 0.1); or with severity of liver disease as judged by prothrombin ratio (P = 1.0) but highest values were observed in patients with cholestatic liver disease. Following parenteral vitamin K there was a significant fall in both the biological activity of VIIIC (36%) and of VIII:CAg (38%) in 13 vitamin K deficient patients (P less than 0.001) but no change in 23 vitamin K replete patients or in the VIIIR:Ag levels in either group. Factor V levels were lower in patients with parenchymal liver disease (0.54 +/- 0.1 units/ml, mean +/- SEM, n = 12; normal range 0.5-1.5 units/ml) than in patients with extrahepatic cholestasis who were vitamin K deficient (1.2 +/- 0.1 units/ml, P less than 0.0001). The levels of protein C antigen, the vitamin K dependent protease which inactivates factors VIII:C and V, was at the lower end of the range in both groups (0.7 +/- 0.1, mean +/- SEM, n = 18, normal range 0.74-1.4 units/ml). There was no significant change in either protein C antigen or factor V following vitamin K. The discrepancy between the biological activity of factor VIII and the antigen levels could represent accumulation of partially degraded factor VIII or production of a hypoactive form. There is no evidence that the reduction in VIIIC and VIII:CAg following vitamin K was mediated by protein C.

Topics: Adolescent; Adult; Aged; Antigens; Factor V; Factor VIII; Female; Glycoproteins; Humans; Liver Diseases; Male; Middle Aged; Platelet Aggregation; Protein C; Ristocetin; Vitamin K; Vitamin K Deficiency; von Willebrand Factor

Topics: Hemorrhage; Humans; Infant, Newborn; Vitamin K; Vitamin K Deficiency

Topics: Age Factors; Breast Feeding; Factor IX; Factor VII; Factor X; Female; Humans; Infant; Infant Nutritional Physiological Phenomena; Infant, Newborn; Pregnancy; Prothrombin; Risk; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Cephalosporins; Colon; Humans; Hypoprothrombinemias; Liver; Nutrition Disorders; Vitamin K; Vitamin K Deficiency

Topics: Humans; Vitamin K; Vitamin K Deficiency

Topics: Breast Feeding; Female; Humans; Infant; Infant, Newborn; Vitamin K; Vitamin K Deficiency

Topics: Animals; Blood Coagulation Disorders; Blood Coagulation Tests; Disease Outbreaks; Female; Hemorrhage; Male; Swine; Swine Diseases; Vitamin K; Vitamin K Deficiency

Topics: Breast Feeding; Humans; Infant; Infant, Newborn; Milk, Human; Vitamin K; Vitamin K Deficiency

Topics: Humans; Infant; Vitamin K; Vitamin K Deficiency

The stereochemistry of the hydrogen abstraction in the vitamin K-dependent carboxylation of synthetic peptides has been investigated; the carboxylation rates of various peptidic substrates containing a stereospecifically 4-monodeuterated glutamic acid residue have been compared to that of nondeuterated peptides. A significant isotope effect was found only with the substrates containing (4S)-4-deuterated glutamic acid. These data reveal that the rat liver microsomal vitamin K-dependent carboxylase acts stereospecifically in abstracting the 4-pro-S hydrogen of the glutamyl residue. The low values of the measured isotope effects indicate that the hydrogen abstraction does not constitute a limiting step in the carboxylation mechanism.

Topics: Animals; Carbon Dioxide; Carbon Radioisotopes; Chemical Phenomena; Chemistry; Deuterium; Glutamates; Glutamic Acid; Hydrogen; Kinetics; Microsomes, Liver; Oligopeptides; Rats; Structure-Activity Relationship; Vitamin K; Vitamin K Deficiency

Thirteen patients who were treated with cephem antibiotics developed blood coagulation disorders due to vitamin K deficiency. At the time of detection of prolongation of the prothrombin time, cefazolin was being administered in four cases, cefmetazole and latamoxef (moxalactam) in three cases each, and cefoperazone, cefpiramide and ceftazidime in one case each. Bleeding occurred in ten patients, but administration of vitamin K rapidly eliminated the prothrombin time prolongation and the haemorrhagic tendency. To date, we have not detected prothrombin time prolongation or a haemorrhagic tendency with cefotaxime, ceftizoxime, cefotiam, cefoxitin or cefsulodin. Thus, different cephem antibiotics show different effects on the prothrombin time.

Topics: Aged; Bacteria; Blood Coagulation Factors; Cefazolin; Cefmetazole; Cefoperazone; Ceftazidime; Cephalosporins; Cephamycins; Female; Hemorrhage; Humans; Injections, Intravenous; Intestines; Male; Moxalactam; Vitamin K; Vitamin K Deficiency

Topics: Breast Feeding; Cerebral Hemorrhage; Female; Humans; Infant; Infant, Newborn; Male; Milk, Human; Vitamin K; Vitamin K Deficiency

The protein C level was determined, on cord blood, for 30 healthy newborns by electro-immuno assay using a monospecific antiserum. For the newborns the mean level of protein C related antigen is about one third of normal adults' mean level. There is a good correlation between Protein C related antigen and prothrombin related antigen. The low level of these vitamin-K-dependent proteins is probably a consequence of partial liver immaturity at birth. Using two-dimensional immuno-electrophoresis we were unable to detect subcarboxylated forms of protein C. However these abnormal forms could be seen in vitamin-K deficiencies of neonates.

Topics: Administration, Oral; Adult; Age Factors; Anticoagulants; Antigens; Blood Coagulation Factors; Blood Proteins; Female; Fetal Blood; Glycoproteins; Humans; Immunoelectrophoresis, Two-Dimensional; Infant, Newborn; Injections, Intravenous; Protein C; Prothrombin; Vitamin K; Vitamin K Deficiency

A 4-week-old, breast-fed female infant appeared healthy until signs and symptoms of CNS deterioration suddenly occurred. At presentation the infant was found to have a left-sided parietal intracerebral hematoma, markedly prolonged prothrombin time, and partial thromboplastin time, normal platelet count, and jaundice with a total and direct serum bilirubin level of 5.4 mg/dL and 2.6 mg/dL, respectively. Vitamin K1 and fresh frozen plasma returned the prothrombin time and partial thromboplastin time to normal values within 18 hours, suggesting that the infant had severe vitamin K deficiency complicated by intracerebral hemorrhage. Evaluation of the infant's direct hyperbilirubinemia led to the diagnosis of homozygous (pi-type ZZ [PiZZ] ) alpha-1-antitrypsin deficiency. The clinical circumstances predisposing to vitamin K deficiency in newborns and infants are discussed. Based on our observations in this case, we suggest that cholestatic liver disease should be suspected when unexplained vitamin K deficiency occurs in early infancy. The role of vitamin K in hemostasis and the laboratory diagnosis of vitamin K deficiency are discussed as they apply to the evaluation of hemorrhage in newborns and infants.

Topics: alpha 1-Antitrypsin Deficiency; Cerebral Hemorrhage; Cholestasis, Intrahepatic; Female; Humans; Infant, Newborn; Risk; Vitamin K; Vitamin K Deficiency

Previous work from this laboratory has suggested there is a risk of hemorrhagic disease of the newborn (HDNB) in approximately one-third of term neonates, presumably as a result of vitamin K deficiency. Using the same assay for PIVKA (protein induced by vitamin K absence, prothrombin precursor), we studied 46 normal mother-infant pairs at term to investigate the relationship between neonatal and maternal PIVKA status. PIVKA was found in 13 infants (28%) and in seven mothers (15%). Maternal PIVKA status correlated with infant status (p less than 0.03). These data suggest that fetal vitamin K deficiency and risk of HDNB may be a consequence of maternal deficiency of the vitamin.

Topics: Adult; Biomarkers; Female; Humans; Infant, Newborn; Postpartum Period; Pregnancy; Protein Precursors; Prothrombin; Risk; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Detailed coagulation studies were done prospectively on 43 patients with biliary atresia who had undergone Kasai operation (hepatic portoenterostomy). Patients were divided into three groups based on levels of factor V, factor II, and Echis II and/or response to vitamin K: no coagulopathy (46.5% of patients); coagulopathy of liver disease (30.2% of patients); and coagulopathy of vitamin K deficiency (23.3% of patients). Patients with the coagulopathy of liver disease had significantly lower levels of factors XII, V, and antithrombin III as well as longer thrombin times than patients with no coagulopathy or vitamin K deficiency. Factor V levels were decreased only in patients with more advanced liver disease; normal levels of factor V were not usually helpful in differentiating liver disease and vitamin K deficiency. The prothrombin time, factor VII-X levels, and factor II levels were significantly different for all three groups; the most abnormal values occurred in the vitamin K-deficient group. Comparison of the Echis II level to factor II coagulant activity was helpful in deciding whether a coagulopathy was due to liver disease, vitamin K deficiency, or both. Factor VIII levels were elevated in all groups. Factor VIII coagulant activity was significantly higher by the two-stage (TGT) method than by the one-stage (PTT) method. Hypersplenism causing neutropenia and thrombocytopenia was commonly seen after the age of 5 years. Vitamin E deficiency was more common than vitamin K deficiency; however, all vitamin K-deficient patients were vitamin E deficient. Coagulation status correlated well with hepatobiliary scan data, but not serum bilirubin levels. Recommendations for treatment of patients with vitamin K deficiency and/or liver disease are discussed.

Topics: Bile Duct Diseases; Bile Ducts; Bilirubin; Blood Coagulation Disorders; Child; Child, Preschool; Humans; Infant; Liver Diseases; Platelet Count; Vitamin E; Vitamin K; Vitamin K Deficiency

Coagulation studies were performed on 16 children with gram-negative septicemia without the complications of septic shock, liver disease, malnutrition, or laboratory evidence of classic disseminated intravascular coagulation (DIC). Ten (63%) of the 16 cases were found to have abnormal partial thromboplastin and/or prothrombin times. The coagulopathy was caused by a reduction in the vitamin K-dependent coagulation factors. The mechanism that produced this coagulopathy was not known, but evidence was found that suggested that endotoxin may interfere with the vitamin K-carboxylation reaction. The data indicated that abnormal coagulation screening test results in children with gram-negative septicemia were not specific for DIC and that a significant number of patients had a coagulopathy not related to DIC.

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Child; Child, Preschool; Gram-Negative Bacteria; Humans; Sepsis; Vitamin K; Vitamin K Deficiency

Vitamin K-dependent carboxylation of synthetic Phe-Leu-Glu-Glu-Val by rat liver microsomes yields a secondary product, which has been identified as Leu-Gla-Glu-Val. Similar results are obtained with other synthetic substrates. The microsomal preparation has been shown to contain an aminopeptidase activity which splits carboxylation products and substrates but is unable to hydrolyse the Leu-Gla peptide bond.

Topics: Aminopeptidases; Animals; Carbon Radioisotopes; Kidney; Kinetics; Leucyl Aminopeptidase; Microsomes, Liver; Oligopeptides; Rats; Swine; Vitamin K; Vitamin K Deficiency

A patient with acute renal failure and gram-negative septicemia developed hypoprothrombinemia during treatment with cefoperazone. The coagulation defect was corrected by vitamin K administration. A multifactorial pathogenetic mechanism of vitamin K deficiency that developed during treatment with parenteral antibiotics is presented.

Topics: Cefoperazone; Humans; Hypoprothrombinemias; Male; Middle Aged; Sepsis; Vitamin K; Vitamin K Deficiency

Hydroxy vitamin K [3(2)-hydroxy-2,3- dihydrovitamin K1] has been identified as a quantitatively important metabolite of injected vitamin K epoxide in vivo. The metabolite has been isolated and identified by comparison of its UV, mass spectra and high-performance liquid chromatography (HPLC) retention times with those of synthetic standards, and by its characteristic conversion to vitamin K quinone on treatment with the base triethylamine. This metabolite is formed from the vitamin K epoxide, not from the vitamin K quinone and can represent up to 3.5% of dose and 13% of hexane-extractable metabolites present in liver 1 hour after injection of 330 micrograms vitamin K1 epoxide per kilogram body weight. It is formed in both normal and warfarin-resistant rat strains, but to a significantly greater extent in the latter. Unlike the hydroxy vitamin K formed by warfarin-resistant rat liver microsomes in vitro, the metabolite formed from racemic vitamin K epoxide in vivo was not optically active, nor was its formation inhibited by coumarin anticoagulants under conditions that completely blocked vitamin K epoxide reduction in vivo. On this basis, hydroxy vitamin K formation in vivo differs from its formation in vitro; it is not a product of vitamin K epoxide reductase in vivo, but of some other possibly non-enzymatic reaction.

Topics: Animals; Chromatography, High Pressure Liquid; Drug Resistance; Liver; Male; Mixed Function Oxygenases; Rats; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Vitamin K Epoxide Reductases; Warfarin

Topics: Adult; Aged; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Protein Electrophoresis; Female; Humans; Male; Prothrombin; Vitamin K; Vitamin K Deficiency

Two breast fed infants had late manifestations of Vitamin K deficiency. No underlying disease was found in the first case. The second patient was found to have alpha 1-Antitrypsin deficiency (Pi type ZZ). The latter patient initially responded well to a single dose of vitamin K administered orally (3 mg). However, three weeks later, he was admitted to our hospital with severe intracranial hemorrhage due to severe vitamin K deficiency. Vitamin K requirements in infants and clinical characteristics of vitamin K deficiency in infants older than 1 week are discussed.

Topics: Blood Coagulation Tests; Breast Feeding; Cerebral Hemorrhage; Female; Hemorrhagic Disorders; Humans; Infant; Infant, Newborn; Male; Vitamin K; Vitamin K Deficiency

Topics: Breast Feeding; England; Female; Humans; Infant, Newborn; Male; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Blood Coagulation; Blood Coagulation Factors; Cephalosporins; Cephamycins; Colectomy; Female; Humans; Middle Aged; Moxalactam; Postoperative Care; Vitamin K; Vitamin K Deficiency

Vitamin K3 inhibits the conversion of benzo(a)pyrene to its more polar metabolites in an in vitro rat liver microsomal system. Vitamin K3 also inhibits benzo(a)pyrene metabolism in rat liver fragments and reduces its mutagenicity in the Ames test. Higher concentrations of vitamin K3 are required to comparably reduce benzo(a)pyrene metabolism when the microsomal system has been induced with 3-methylcholanthrene. High pressure liquid chromatography analysis of the products of benzo(a)pyrene metabolism shows a uniform reduction of all the metabolic products. When tumors were induced in ICR/Ha female mice by the intraperitoneal injection of benzo(a)pyrene, those mice given vitamin K3 before or both before and after benzo(a)pyrene had a slower rate of tumor appearance and tumor death rate as compared with those receiving benzo(a)pyrene alone. However, vitamin K1 increased the rate of tumor death while vitamin K deprivation and warfarin decreased the rate of tumor appearance and death in benzo(a)pyrene-injected mice. These studies indicate that vitamin K3 is an inhibitor of aryl hydrocarbon hydroxylase and reduces the carcinogenic and mutagenic metabolites in vitro, and inhibits benzo(a)pyrene tumorigenesis in vivo. That vitamin K1 enhances the benzo(a)pyrene effect while warfarin and vitamin K deficiency inhibit benzo(a)pyrene tumorigenesis indicates that vitamin K1, vitamin K deprivation, or possibly blockade of its metabolic cycle also modulates benzo(a)pyrene metabolism in vivo but by a mechanism or at a site different from the vitamin K3 effect. The vitamin K series should be considered as capable of serving a regulatory function in the metabolism of benzo(a)pyrene and possibly other compounds metabolized through the mixed function oxidase system.

Topics: Aflatoxin B1; Aflatoxins; Animals; Benzo(a)pyrene; Benzopyrenes; Female; Male; Mice; Mice, Inbred ICR; Microsomes, Liver; Mutagenicity Tests; Mutation; Neoplasms, Experimental; Rats; Rats, Inbred Strains; Vitamin K; Vitamin K 1; Vitamin K 3; Vitamin K Deficiency

The effects of sodium salicylate on synthesis of a vitamin K-dependent plasma coagulation protein, Factor II (prothrombin) was studied using the isolated rat liver perfused for 10 hours in vitro. Cumulative synthesis of Factor II was measured by a standard coagulation assay, by activation with E. carinatus venom, and by rocket immunoelectrophoresis. When sodium salicylate 5 mg or 25 mg was added to the liver perfusate (volume 100 ml) at the outset of the perfusion, cumulative synthesis of both coagulation activity and immunoreactive protein was significantly less than that seen in control perfusions containing no salicylate. The inhibitory effect of salicylate was prevented by pretreatment of rat liver donors with supplemental vitamin K injected 24 hours before sacrifice. Although some interaction between salicylate and vitamin K was apparent from these experiments, the results from vitamin K-deficient rat liver donors were quite different from those containing salicylate. There was no assayable Factor II coagulation activity produced in 10 hours of perfusion of vitamin K-deficient rat livers, but cumulative synthesis of immunoreactive Factor II was quite comparable to that seen in control perfusions.

Topics: Animals; Drug Interactions; Liver; Perfusion; Prothrombin; Rats; Sodium Salicylate; Vitamin K; Vitamin K Deficiency

Haemorrhages were observed in four wholly breastfed infants beyond the neonatal period. These infants were observed within a period of 8 weeks and showed the following characteristics: 1. Onset of bleedings was unexpected and without prior indication. 2. They were of a serious nature and involved the CNS in two children. 3. In all cases infants between 4 and 6 weeks of life were affected. 4. All infants had been wholly breastfed. 5. All were male. 6. There was a prompt improvement after administration of vitamin K or after blood or blood derivatives. Although preliminary own investigations do not indicate general lowering of vitamin-K-dependent coagulation factors in wholly breastfed infants in the postneonatal period, these 4 cases observed within a short time confirm the necessity to consider vitamin K deficiency in haemorrhages in infants in the postneonatal period. Diagnostic steps have to be initiated immediately.

Topics: Blood Transfusion; Breast Feeding; Cerebral Hemorrhage; Hemorrhage; Humans; Infant; Infant, Newborn; Male; Vitamin K; Vitamin K Deficiency

Topics: Female; Humans; Hypoprothrombinemias; Infant; Milk, Human; Vitamin K; Vitamin K Deficiency

A plasma factor, "coagulopoietin", present in animals with depleted vitamin K-dependent coagulation factors, appears to enhance activity of these factors in normal animals. We have investigated the effects of "coagulopoietin" on synthesis of certain coagulation proteins by the isolated rat liver perfused for eight hours. Liver donor rats received plasma injections from vitamin K-deficient rats or from normal rats 24 hr before sacrifice. Coagulation activity of Factor VII and Factor II in liver perfusate samples was measured with a coagulation assay; Factor II synthesis was also measured by rocket immunoelectrophoresis and by activation with E. carinatus venom. Cumulative hepatic synthesis of Factor VII coagulation activity was increased by 43% when rat liver donors received vitamin K-deficient rat plasma compared to normal rat plasma. Cumulative synthesis of Factor II coagulation activity was increased by 51%, but synthesis of the protein measured immunologically or by activation with venom was not affected. The "coagulopoietin" factor in these studies appears to increase measurable coagulation factor activity without increasing total protein synthesis.

Topics: Animals; Blood Coagulation Factors; Factor VII; Liver; Male; Perfusion; Prothrombin; Rats; Rats, Inbred Strains; Vitamin K; Vitamin K Deficiency

Newborns have low levels of the vitamin K dependent clotting factors. Early studies were suggestive of vitamin K deficiency. Recently these findings were questioned by studies that failed to detect signs of vitamin K deficiency in the clotting system of newborns using more specific methods, while other studies did find signs of vitamin K deficiency using the same methods. The question was finally solved by direct measurement of vitamin K showing very low levels of the vitamin in the serum of newborns immediately after birth. Whether vitamin K supplementation to the mother reduces the incidence of vitamin K induced changes in the clotting system of newborns remains to be elucidated. In the meantime it seems prudent to administer parenteral vitamin K prophylactically to all newborns immediately after birth.

Topics: Adult; Blood Coagulation Disorders; Chromatography, High Pressure Liquid; Female; Humans; Immunoelectrophoresis, Two-Dimensional; Infant, Newborn; Infant, Newborn, Diseases; Maternal-Fetal Exchange; Pregnancy; Prothrombin; Vitamin K; Vitamin K Deficiency

Activity of the rat liver microsomal vitamin K-dependent carboxylase has been studied at various concentrations of detergent. The activity which could be solubilized by 0.25% Triton X-100 was low but could be greatly increased if vitamin K-deficient rats were given vitamin K a few minutes before they were killed. At higher concentrations of Triton, more activity was solubilized and this effect was not seen. In vitro carboxylation of endogenous microsomal proteins was decreased by 80-90% if vitamin K was administered 1 min before rats were killed, but the amount of assayable prothrombin precursor was decreased by only 20%. Decarboxylated vitamin K-dependent rat plasma proteins were not substrates for the carboxylase and did not influence peptide carboxylase activity significantly. Purified microsomal prothrombin precursors did, however, stimulate carboxylation of peptide substrate and were used as a substrate for the carboxylase in a preparation from precursor depleted vitamin K-deficient rats.

Topics: Animals; Carbon-Carbon Ligases; Detergents; Enzyme Activation; Ligases; Male; Microsomes, Liver; Protein Precursors; Prothrombin; Rats; Surface-Active Agents; Vitamin K; Vitamin K Deficiency

Vitamin K content of liver and feces from male rats fed diets containing butylated hydroxytoluene (BHT) was estimated by a chick bioassay method to investigate the mechanism of BHT-induced decreases in the activities of vitamin K-dependent clotting factors. The concentration of vitamin K in the liver of rats receiving BHT was reduced as compared to that of control rats. Conversely, the concentration of vitamin K in the feces from rats receiving BHT increased more than that from control rats. The vitamin K deficiency induced by BHT might be due to effects of BHT on absorption and excretion of vitamin K.

Topics: Animals; Bacteria; Butylated Hydroxytoluene; Feces; Intestinal Mucosa; Liver; Male; Rats; Rats, Inbred Strains; Vitamin K; Vitamin K Deficiency

Rat liver microsomes contain a Triton X-100 solubilizable vitamin K-dependent carboxylase activity that converts specific glutamyl residues of a microsomal prothrombin precursor to gamma-carboxyglutamyl residues. This activity has been studied in partially (0.25% Triton X-100) and completely (1.0% Triton X-100) solubilized rat liver microsomal preparations. The rate of vitamin K-dependent carboxylation of endogenous microsomal protein precursors was very rapid in the completely solubilized liver microsomal preparation, and carboxylation of an exogenous peptide substrate (Phe-Leu-Glu-Glu-Leu) proceeded at the same time. In the partially solubilized liver microsomal preparation, the rate of protein carboxylation was greatly reduced, and a lag in carboxylation of the exogenous substrate was observed. When microsomal preparations which were depleted of endogenous precursors were used, this lag was eliminated. These data suggest that both substrates utilize the same microsomal pool of carboxylase and that the fraction of the carboxylase bound to the endogenous precursors is not immediately available to exogenous substrates.

Topics: Animals; Carboxylic Ester Hydrolases; Hypoprothrombinemias; Kinetics; Male; Microsomes, Liver; Protein Precursors; Rats; Rats, Inbred Strains; Vitamin K; Vitamin K Deficiency

The molar ratio of menadione (vitamin K3) to beta-cyclodextrin in the microcrystalline inclusion complex showed this to be 1:3 with a menadione content of approximately 4.1-4.3%. Complexes with higher vitamin content could not be prepared. Bound and free vitamin can be readily separated by sublimation in vacuum. The menadione is highly stable in complexed form; in dry state it is released only when cyclodextrin is destroyed by heating to about 300 degrees C. Complexed menadione does not react with amino acids. Solubility and dissolution rate are strongly increased. Treating hypovitaminotic chickens with equivalent doses of menadione or menadione-beta-cyclodextrin complex and monitoring blood clotting times, recalcification times and prothrombin times the complex proved to be at least as effective as--or even somewhat more potent than--free vitamin. 1.5-2.0 micrograms/animal/d free or complexed menadione was sufficient to cover the daily vitamin K needs of chickens.

Topics: Animals; beta-Cyclodextrins; Chemical Phenomena; Chemistry, Physical; Chickens; Crystallization; Cyclodextrins; Dextrins; Nephelometry and Turbidimetry; Poultry Diseases; Starch; Vitamin K; Vitamin K Deficiency

Relative antihemorrhagic properties of structural analogs of transphylloquinone (vitamin K1) have been determined by curative prothrombin time tests with vitamin K-deficient chicks. Analogs (where applicable) and the phylloquinone standard had (all-) rac-trans configuration, and all compounds were well characterized (structure, purity, trans: cis). Compounds were administered as single oral doses according to the up-and-down procedure. Estimation of mean effective doses allowed a reliable calculation of relative activities for analogs in comparison with vitamin K1 standard. 2', 3'-Dihydro-phylloquinone had a relative activity of only 6.7%, i.e. it was about 15 times less active than phylloquinone. Further reduction of this analog led to 2',3',5,6,7,8-hexahydro-phylloquinone which was completely inactive. Analogs with oxygen functions in the side chain, 6'-hydroxy-K1, 6'-oxo-K1, and 7'-hydroxy-6'-oxo-K1, displayed relative activities of 20.5%, 31.9%, and 30.5%, respectively. Phylloquinone-2,3-epoxide was 1.7 times more active than the phylloquinone standard. An analog with a 7-carbon side chain ending with a carboxy group (in mammals a urinary metabolite of vitamin K1) and its corresponding ethyl ester derivative were practically inactive.

Topics: Animals; Chemical Phenomena; Chemistry; Chickens; Dose-Response Relationship, Drug; Female; Hemorrhage; Prothrombin Time; Vitamin K; Vitamin K Deficiency

During prothrombin biosynthesis, glutamyl residues in prothrombin precursor proteins are carboxylated to gamma-carboxyglutamyl residues by a vitamin K dependent carboxylase. Calcium-dependent and calcium-independent rat prothrombin antibody subpopulations have been produced and utilized to study the liver microsomal precursors of prothrombin that accumulate when vitamin K action is blocked. A substantial portion of the precursor pool accumulating in the vitamin K deficient or warfarin-treated rat will react with a Ca2+-dependent antibody at high calcium concentration and appears to be partially carboxylated. During in vitro incubation in the presence of vitamin K, the fraction of the precursor pool which is tightly bound to the microsomal membrane appears to be the preferred substrate for the vitamin K dependent carboxylation. A small amount of completely carboxylated rather than a large amount of partially carboxylated products are produced during these incubations. Treatment with a Sepharose-bound prothrombin antibody demonstrated that about 20-25% of the total carboxylated microsomal protein precursor pool consists of prothrombin precursors. This treatment removes an equal amount of total carboxylase activity, and the enzyme is active in this carboxylase precursor-antibody complex.

Topics: Animals; Antibodies; Calcium; Carboxy-Lyases; Immunosorbent Techniques; Male; Microsomes, Liver; Protein Precursors; Prothrombin; Rats; Vitamin K; Vitamin K Deficiency; Warfarin

The dithiothreitol-dependent vitamin K and vitamin K 2,3-epoxide hepatic microsomal reductase activities of warfarin-susceptible and warfarin-resistant rats were compared to gain insight into the role(s) of these activities in vitamin K metabolism and function. In microsomes from resistant rats, 3- to 4-fold more warfarin was required to produce 50% inhibition (I50) of vitamin K reduction to vitamin K hydroquinone than in microsomes from susceptible rats. For the reduction of vitamin K 2,3-epoxide to vitamin K a 6-fold higher warfarin concentration was required. In microsomes from resistant rats, the I50 warfarin concentration required to inhibit gamma-carboxylation of microsomal precursor protein was also 4-fold higher with vitamin K as substrate and was 6-fold higher with the epoxide as substrate than in microsomes from susceptible rats. Collectively, these data suggest that the vitamin K reductase contributes to the metabolism of vitamin K in intact rats and that warfarin inhibition of both the vitamin K and vitamin K 2,3-epoxide reductases is involved in its anticoagulant effect.

Topics: Animals; Dithiothreitol; Drug Resistance; Kinetics; Male; Microsomes, Liver; Mixed Function Oxygenases; NAD(P)H Dehydrogenase (Quinone); Quinone Reductases; Rats; Vitamin K; Vitamin K Deficiency; Vitamin K Epoxide Reductases; Warfarin

Topics: Animals; Blood Coagulation Factors; Blood Coagulation Tests; Breast Feeding; Humans; Infant; Infant Food; Milk; Vitamin K; Vitamin K Deficiency

Vitamin K-1 epoxide, the major metabolite of vitamin k-1, has similar activity to vitamin K-1 in inducing prothrombin synthesis and protein carboxylation. The high activity of K-1 epoxide could be due to its conversion to vitamin K-1 hydroquinone without going through vitamin K-1. A logical intermediate in this conversion would be vitamin K-1 epoxide-1,4-diol. The epoxide diol was synthesized and clearly stimulated prothrombin synthesis in vitamin K deficient rats at a minimum dose of 100 micrograms/kg body weight. Since vitamin K-1 produced a similar response at a minimum dose of 1 microgram/kg, the epoxide diol had about 1% of the activity of vitamin K-1. [3H]K-1 or [3H]epoxide could not be detected as metabolites of [3H]epoxide diol indicating that the activity of epoxide diol was probably not due to its conversion to K-1 hydroquinone, since any [3H]hydroquinone formed would be oxidized in air to [3H]K-1 during analysis. Vitamin K-1 epoxide diol represents a new type of structure possessing vitamin K activity. It is probably not active itself but has to be converted to an active compound since there is a delay in the response to the diol and the activity is completely blocked by Warfarin.

Topics: Animals; Prothrombin; Rats; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Warfarin

Topics: Adolescent; Adult; Child; Child, Preschool; Choline; Humans; Infant; Nutritional Requirements; Vitamin E; Vitamin E Deficiency; Vitamin K; Vitamin K Deficiency; Vitamins

Topics: Animals; Cholic Acids; Detergents; Ligases; Male; Microsomes, Liver; Octoxynol; Polyethylene Glycols; Rats; Rats, Inbred Strains; Solubility; Surface-Active Agents; Vitamin K; Vitamin K Deficiency

The renal vitamin K-dependent gamma-glutamyl carboxylase was present in microsomes prepared from the renal cortex as well as the inner and outer medulla of several species. When glomeruli were isolated from either dog or rat renal cortex, microsomes prepared from these glomeruli were devoid of carboxylase activity. Proximal tubules were isolated from rabbit renal cortex; microsomes derived from these tubules had easily measurable carboxylase activity. The experiments demonstrate that the vitamin K-dependent gamma-glutamyl carboxylase is located in renal tubule cells. Since the enzyme is found not only in cortex but also inner and outer medulla, its distribution is not restricted to specific tubule segments.

Topics: Animals; Carbon-Carbon Ligases; Dogs; Kidney Cortex; Kidney Medulla; Kidney Tubules; Ligases; Liver; Male; Microsomes; Organ Specificity; Rabbits; Rats; Species Specificity; Vitamin K; Vitamin K Deficiency

Topics: Female; Humans; Infant; Male; Purpura; Vitamin K; Vitamin K Deficiency

Topics: Humans; Infant; Prothrombin Time; Vitamin K; Vitamin K Deficiency

Owing to the lack of sensitivity and/or selectivity of the existing chemical assays, vitamin K deficiency has always been diagnosed indirectly by measuring its effect on blood coagulation. We used our recently developed multidimensional liquid chromatographic assay for what is, to the best of our knowledge, the first systematic investigation of physiological vitamin K levels in human blood. It allowed the unequivocal demonstration of trans-phylloquinone (vitamin K1) and its quantification down to a level of 0.5 nanogram per milliliter of serum (ng/ml. In healthy adults, a mean serum concentration of 2.6 ng/ml was found, with a normal range of 0.9 to 7.8 ng/ml. These values apparently are distributed in a log-normal way.

Topics: Adult; Chromatography, High Pressure Liquid; Fasting; Humans; Reference Values; Vitamin K; Vitamin K Deficiency

Topics: Humans; Infant, Newborn; Infant, Premature; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding; Vitamins

Crude rat liver microsomal preparations catalyze a reduced vitamin K- and oxygen-dependent carboxylation of peptide-bound glutamyl residues to gamma-carboxyglutamyl residues. The same preparations convert reduced vitamin K to its 2,3-epoxide. The stoichiometry of this relationship has been investigated. At saturating concentrations of CO2, equal amounts of vitamin K 2,3-epoxide and gamma-carboxyglutamic acid are formed. As the CO2 concentration is lowered, this ratio shifts to a large excess of epoxide. Alterations in glutamyl substrate concentration or Mn2+ concentration cause equal alterations in both activities, while addition of KCN stimulated epoxidation and inhibited carboxylation. The release of 3H from a gamma-[3H]glutamyl substrate was tightly coupled to epoxide formation, and both of these activities were inhibited by glutathione peroxidase. These data are consistent with a reaction mechanism in which an oxygenated form of vitamin K activates the substrate glutamyl residue by hydrogen removal in a reaction that is coupled to vitamin K epoxide formation.

Topics: Animals; Carbon-Carbon Ligases; Chlorides; Kinetics; Ligases; Manganese; Manganese Compounds; Microsomes, Liver; Mixed Function Oxygenases; Potassium Cyanide; Rats; Vitamin K; Vitamin K 2; Vitamin K Deficiency; Vitamin K Epoxide Reductases

Topics: Aged; Female; Humans; Hypoprothrombinemias; Prothrombin; Sulfisoxazole; Vitamin K; Vitamin K Deficiency

Topics: Animals; Blood Coagulation Factors; Factor X; Lung Neoplasms; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; Neoplasms, Experimental; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Bacteria; Cefamandole; Cephalosporins; Depression, Chemical; Gastrointestinal Hemorrhage; Humans; Intestines; Vitamin K; Vitamin K Deficiency

Five patients developed vitamin K-related abnormalities in blood coagulation during treatment with parenteral cephalosporin or cephamycin antibiotics. All the patients had significantly impaired renal function and complicated medical problems. The coagulation defect was corrected with vitamin K therapy.

Topics: Adult; Aged; Cephalosporins; Female; Humans; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Sepsis; Urinary Tract Infections; Vitamin K; Vitamin K Deficiency

An acetone powder, prepared from the liver microsomes of vitamin K-deficient rats, retains an active vitamin K-dependent gamma-glutamyl carboxylase. While the basic requirements of the enzyme are similar to those of the carboxylase of either resuspended microsomes or detergent-solubilized microsomes, the acetone powder preparation reveals some additional properties of the carboxylase. Carboxylation of the synthetic pentapeptide substrate phenylalanylleucyl-glutamyl-glutamyl-valine can occur in the absence of nonionic detergent; however, when vitamin K hydroquinone drives the acetone powder carboxylation nonionic detergent is require for maximal activity. Experiments are described in which the acetone powder is incubated with the pentapeptide, pelleted by centrifugation, resuspended with fresh reactants, and incubated again. They suggest that the low V for the carboxylase, observed by all investigators, is, at least in part, not the result of irreversible enzyme inactivation nor depletion of reactants, but rather accumulation of a yet to be identified inhibitor(s). The acetone powder prepared from microsomes derived from livers of nutritionally normal cows contains vitamins vitamin K-dependent gamma-glutamyl carboxylase. This enzyme can be solubilized from the powder using Triton X-100 and could provided a large supply of starting material for enzyme purification.

Topics: Acetone; Animals; Carbon-Carbon Ligases; Cattle; Kinetics; Ligases; Male; Microsomes, Liver; Oligopeptides; Powders; Rats; Vitamin K; Vitamin K Deficiency

Topics: Animals; Epoxy Compounds; Glutamates; Ligases; Male; Microsomes, Liver; Mixed Function Oxygenases; Prothrombin; Rats; Vitamin K; Vitamin K Deficiency

Attempts to purify the vitamin K-dependent carboxylation system from rat liver microsomes have not yet met with success. Purification procedures result in low yields of activity even after relatively mild separation methods. We have been able to demonstrate that one reason for these failures is that there are at least two components (which can be separated) necessary for the reaction. Recombination of the separated components is possible if the detergent (Triton X-100) concentration is lowered and ethylene glycol is added to the system. Under these conditions, vitamin K-dependent carboxylation of synthetic pentapeptide (Phe-Leu-Glu-Glu-Leu) can be totally reconstituted.

Topics: Animals; Carbonates; Glutamates; Ligases; Male; Microsomes, Liver; Oligopeptides; Peptides; Prothrombin; Rats; Vitamin K; Vitamin K Deficiency

Vitamin K-dependent carboxylation activity measured with pentapeptide substrate (Phe-Leu-Glu-Glu-Leu) gradually decreases upon in vivo injection of vitamin K to vitamin K-deficient rats. A decrease in pentapeptide carboxylation can also be observed by the in vitro addition of antibodies against prothrombin and other vitamin K-dependent proteins to the soluble system derived from vitamin K-deficient rat liver microsomes. In both cases, adding back in vitro partially decarboxylated vitamin K-dependent proteins or purified hepatic prothrombin precursor restores the level of pentapeptide carboxylation. After warfarin treatment, a 3-fold increase in carboxylation results, which can be abolished by giving cycloheximide along with the warfarin. However, the resulting decreased activity is restored by the in vitro addition of partially decarboxylated vitamin K-dependent proteins. These data are consistent with the hypothesis that (after warfarin treatment) increased peptide carboxylation is primarily due to activation of the system by precursor proteins, rather than synthesis of an increased amount of enzyme.

Topics: Animals; Antigen-Antibody Reactions; Carbon Dioxide; Cycloheximide; Hypoprothrombinemias; Immune Sera; Kinetics; Male; Microsomes, Liver; Oligopeptides; Proteins; Prothrombin; Rats; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Animals; Carbon-Carbon Ligases; Kinetics; Ligases; Male; Microsomes, Liver; Rats; Structure-Activity Relationship; Vitamin K; Vitamin K Deficiency

Vitamin K is a required cofactor for a microsomal enzyme system that carboxylates glutamyl residues of precursor proteins to gamma-carboxyglutamyl residues in completed proteins. These residues have recently been shown to be present in a number of proteins other than the long-recognized vitamin K-dependent clotting factors, and it is apparent that this reaction is much more widespread than once thought. This enzyme has been extensively studied in rat liver and has been shown to require the reduced form of vitamin K, O2, and CO2. This enzyme activity is induced in vitamin K-deficient animals, and the activity has been localized at the lumen surface of the rough microsome fraction. Liver microsomes also contain enzymes that oxidize the vitamin to its 2,3-epoxide and reduce the epoxide back to the reduced vitamin. The carboxylase activity and epoxidase activity appear to share a common oxygenated intermediate, and the available data suggest that this may be a hydroperoxide of the vitamin. Current evidence would indicate that the role of vitamin K is to labilize the gamma-hydrogen of the substrate for CO2 attack rather than to activate or transfer the CO2.

Topics: 1-Carboxyglutamic Acid; Animals; Blood Coagulation Factors; Carbon-Carbon Ligases; Kinetics; Ligases; Liver; Microsomes, Liver; NADH, NADPH Oxidoreductases; Proteins; Rats; Vitamin K; Vitamin K Deficiency

Topics: Adolescent; Adult; Child; Female; Humans; Infant, Newborn; Male; Maternal-Fetal Exchange; Phenytoin; Pregnancy; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Hypoprothrombinemia occurs in newborn infants, but it is unclear whether this is the result of reduced production of Factor II precursor or a vitamin K deficient state. In this study, 76 cord blood specimens were analyzed for functional factor coagulant activity and levels of Factor II antigen as determined by electroimmunoassay. In 40 normal term infants, CA = 30% +/- 1.6 (mean +/- SEM) and Ag = 44% +/- 2.3; in 17 normal preterm infants CA = 30% +/- 1.0 and Ag = 31% +/- 4.2; and in 50 normal adults CA = 83 +/- 3 and Ag = 91 +/- 4. In the term infants the average ratio of CA:Ag was 0.90 and in the preterm infants 0.96, both values being similar to those in adults and suggesting underproduction of the precursor form. In 19 term infants who experienced complications of pregnancy and/or delivery, the ratio was 0.76; seven of these ratios were less than 0.70 (range 0.40 to 0.69). These data show that hypoprothrombinemia is common in infant cord blood and is most marked in preterm infants. In the normal infants the CA:Ag ratios were normal, suggesting that the hypoprothrombinemia is the result of reduced production of the protein and not of vitamin K deficiency. However, term infants with complications of labor and delivery had reduced CA:Ag ratios that were suggestive of vitamin K deficiency.

Topics: Adult; Antigens; Female; Fetal Blood; Humans; Immunoelectrophoresis; Infant, Newborn; Infant, Premature; Prothrombin; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Animals; Castration; Estradiol; Female; Hypophysectomy; Male; Microsomes, Liver; Progestins; Prolactin; Prothrombin; Rats; Testosterone; Vitamin K; Vitamin K Deficiency

Topics: Breast Feeding; Gastrointestinal Hemorrhage; Humans; Infant, Newborn; Male; Time Factors; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Breast Feeding; Hematoma, Subdural; Humans; Infant; Male; Time Factors; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: 1-Carboxyglutamic Acid; Amino Acids; Animals; Blood Coagulation Disorders; Cycloheximide; Female; Half-Life; In Vitro Techniques; Male; Microsomes, Liver; Protein Biosynthesis; Prothrombin; Rats; Sex Factors; Vitamin K; Vitamin K Deficiency; Warfarin

A 6-week-old breast-fed infant presented with vomiting, jaundice, and irritability. Haemorrhage occurred after lumbar puncture, and a coagulation abnormality which responded to vitamin K was found. It would seem prudent to estimate the prothrombin time before invasive procedures in breast-fed infants of this age, or to give vitamin K to such infants when doubt exists about previous vitamin K administration.

Topics: Humans; Infant; Male; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

It has been shown that pregnancy specific beta 1-globulin (SBG) is found in the rat blood serum on the 6--7th day of pregnancy. SBG reaches the maximum by the end of pregnancy and is not detected already at the 3d--4th day after delivery. The placenta is the site of the SBG snythesis. Other organs of the pregnant rat are not able to incorporate radioactive aminoacids into the protein in vitro.

Topics: Animals; Aorta; Ascorbic Acid; Glycosaminoglycans; Rats; Time Factors; Vitamin K; Vitamin K Deficiency

Topics: 1-Carboxyglutamic Acid; Animals; Blood Coagulation Factors; Blood Proteins; Cattle; Factor IX; Factor VII; Factor X; Humans; Prothrombin; Vitamin K; Vitamin K Deficiency

Topics: Animals; Carbon-Carbon Ligases; Cattle; Chickens; Cricetinae; Drug Resistance; Glutamates; Guinea Pigs; Ligases; Male; Mice; Microsomes, Liver; Peptides; Prothrombin; Rabbits; Rats; Species Specificity; Swine; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Animals; Aspirin; Cattle; Copper; Erythrocytes; Kinetics; Male; Microsomes, Liver; Penicillamine; Prothrombin; Rats; Superoxide Dismutase; Tyrosine; Vitamin K; Vitamin K Deficiency

Topics: Animals; Carboxy-Lyases; Kinetics; Male; Microsomes, Liver; Oligopeptides; Rats; Vitamin K; Vitamin K 1; Vitamin K Deficiency

Topics: Humans; Infant, Newborn; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Vitamin K is an essential cofactor for a microsomal carboxylase that converts glutamyl residues in endogenous precursor proteins to gamma-carboxyglutamyl residues in completed proteins. The same microsomal preparations convert vitamin K to its 2,3-epoxide, and it has been suggested that these two reactions (carboxylation and epoxidation) are coupled. Glutathione peroxidase, which reduces hydrogen peroxide and organic hydroperoxides, inhibits both of these reactions in a prepartion of microsomes solubilized by Triton X-100. Catalase has no effect. In the absence of vitamin K, and in the presence of NADPH, tert-butyl hydroperoxide acts as a weak vitamin K analog. At lower concentrations, tert-butyl hydroperoxide is an apparent competitive inhibitor of vitamin K for both the carboxylase and epoxidase reactions. These data are consistent with the hypothesis that both of these vitamin K-requiring reactions involve a common oxygenated intermediate, and that a hydroperoxide of the vitamin is the species involved.

Topics: Animals; Carbon-Carbon Ligases; Catalase; Epoxy Compounds; Glutamates; Glutathione Peroxidase; Kinetics; Ligases; Microsomes, Liver; Peroxides; Prothrombin; Rats; Vitamin K; Vitamin K Deficiency

Haemorrhagic diathesis was a leading symptom in diagnosing celiac disease in 4 patients. In all 4 patients, a duodenal biopsy showed total villous atrophy. Although 3 of the children were typically dystrophic, the weight of the 4th child, an 8 month old boy, was within the normal range. In this patient, who suffered from neither diarrhea nor vomiting, heavy cutaneous and mucous membrane bleeding were the only symptoms of the disease. In all 4 cases the haemorrhagic diathesis could be explained by a low prothrombin complex, whereas the rest of the coagulation tests were normal. After the administration of Vitamin K1 there was an immediate rise in the prothrombin complex and bleeding was quickly stopped. Noteworthy is that due to infections, 3 of the 4 patients, received antibiotics just before the onset of the bleeding. In celiac disease, the conversion from a K-hypovitaminosis into a K-avitaminosis by the administration of antibiotics is discussed.

Topics: Anti-Bacterial Agents; Celiac Disease; Female; Hemorrhagic Disorders; Humans; Infant; Male; Vitamin K; Vitamin K Deficiency

Topics: Animals; Drug Resistance; Glutamates; Ligases; Male; Microsomes, Liver; Mixed Function Oxygenases; Models, Biological; Oxidation-Reduction; Prothrombin; Rats; Vitamin K; Vitamin K Deficiency; Warfarin

When rats were given single or multiple doses of warfarin, the levels of prothrombin and factors VII, IX, and X were depressed, as expected. However, modest reductions of factors V, VIII, XI, and XII, but not of fibrinogen, also occurred. The levels of all eight factors promptly returned to normal when vitamin K1 was given. Warfarin-resistant rats had no depression of any of the eight factors. When vitamin K deficiency was induced by internal or external biliary fistula, factors II-VII-IX-X decreased sharply and factors V-VIII-XI-XII decreased modestly. Again, all depression were promptly reversed by vitamin K1. Isolated livers from warfarinized rats did not generate the classic vitamin K-dependent factors during 5 h of perfusion but did generate small amounts of factors V, XI, and XII, although less than normal. The isolated rat liver apparently does not generate factor VIII.

Topics: Animals; Dose-Response Relationship, Drug; Factor V; Factor VIII; Factor XI; Factor XII; Liver; Male; Perfusion; Rats; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Animals; Chickens; Female; Liver; Male; Protein Precursors; Prothrombin; Rats; Vitamin K; Vitamin K 1; Vitamin K Deficiency

Two patients with acute pancreatitis in pregnancy are described. In both, bleeding from vitamin K deficiency occurred after the initial attack of pancreatitis and the bleeding tendency was successfully treated with vitamin K.

Topics: Acute Disease; Adult; Female; Hematuria; Humans; Pancreatitis; Pregnancy; Pregnancy Complications; Vitamin K; Vitamin K Deficiency

Vitamin K is a component of a membrane-bound enzyme complex which catalyzes the posttranslational carboxylation of peptide-bound glutamate to form the gamma-carboxyglutamate (Gla) residues of prothrombin. The reaction requires reduced vitamin K, bicarbonate, oxygen, and a carboxylase, and does not require ATP. In a Triton X-100 solubilized carboxylase system, it was found that the naphthoquinone ring structure is essential for activity, as is the 2-methyl group. Menaquinone homologs from MK-1 to MK-4 all had carboxylase activity, whereas menadione was inactive. However, dithiothreitol and other thiols form thioethers with menadione, which restores considerable carboxylation activity to the provitamin. Hydrogenation of the beta-gamma double bond in phylloquinone reduced its activity only slightly. The active species of "CO2" utilized in this carboxylation is CO2 and not bicarbonate. Ribosomes contain Gla residues and are labeled with CO2 when whole microsomes are incubated with CO2 in the presence of NADH and vitamin K. About 25% of the activity is releasable with puromycin, suggesting that Gla residues are formed on both the nascent chains and the structural proteins of ribosomes. The deoxycholate-solubilized carboxylase system can be dialyzed to yield membranous vesicles with enhanced carboxylase activity. The warfarin-binding protein from normal rats, but not that from warfarin-resistant rats, further enhances the carboxylase activity of these reformed vesicles.

Topics: 1-Carboxyglutamic Acid; Animals; Carbon Dioxide; Carboxy-Lyases; Carrier Proteins; Glutamates; Intracellular Membranes; Microsomes, Liver; Peptides; Rats; Ribosomal Proteins; Structure-Activity Relationship; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Blood Coagulation Factors; Humans; Infant, Newborn; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Blood Coagulation; Diagnosis, Differential; Humans; Infant, Newborn; Vitamin K; Vitamin K Deficiency

A bleeding syndrome due to severe prothrombin complex deficiency is reported in 93 infants. Most were breast fed (98 per cent), aged 2 weeks to 1 year and there were no serious preceding or associated diseases. Hemorrhagic diathesis, pallor and mild hepatomegaly were the major manifestations. The incidence of intracr anial bleeding was strikingly high (63 per cent) particularly with subdural and subarachnoid hemorrhage. Acute onset, short course and rapid clinical and laboratory improvement after vitamin K therapy were observed. Mortality rate was 35 per cent but has been reduced to 17 per cent since 1969. The location of bleeding, prompt diagnosis and early treatment are the major factors affecting prognosis. Severe prothrombin complex deficiency due to vitamin K deficiency accounted for the pathogenesis of bleeding. Possible causes of vitamin K deficiency were discussed but definite conclusions could not be drawn.

Topics: Cerebral Hemorrhage; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Hypoprothrombinemias; Infant; Infant, Newborn; Male; Subarachnoid Hemorrhage; Syndrome; Vitamin K; Vitamin K Deficiency

Topics: Animals; Cell-Free System; Factor VII; Factor X; Immunodiffusion; Kinetics; Liver; Male; Prothrombin; Rats; Structure-Activity Relationship; Subcellular Fractions; Vitamin K; Vitamin K Deficiency

The coagulopathy induced by vitamin K deficiency commonly results from our lack of awareness of the clinical setting associated with vitamin K deficiency. Thirteen cases are reviewed to illustrate the clinical correlates most frequently observed. Dietary deficiency was always present, but concomitant antibiotic therapy was not an absolute requirement. The postoperative patient is at high risk, as is the patient with cancer or renal failure. Abnormal bleeding was common, but significant hemorrhage occurred only in postoperative patients. Factor assays were helpful and occasionally necessary to make the diagnosis, but a therapeutic trial with parenteral vitamin K was often enough to provide the right diagnosis. Greater awareness of this deficiency syndrome is necessary to avoid the serious morbidity that often results.

Topics: Adult; Aged; Anti-Bacterial Agents; Blood Coagulation Disorders; Humans; Kidney Failure, Chronic; Male; Middle Aged; Neoplasms; Nutrition Disorders; Preoperative Care; Risk; Surgical Procedures, Operative; Vitamin K; Vitamin K Deficiency

Intact male and female albino rats fed a vitamin K-deficient diet develop a plasma prothrombin-proconvertin deficiency. Male rats respond with a precipitous drop to approximately 20-30% of normal plasma levels within 2-5 days, whereas female rats respond at a slower rate. Ethynylestradiol, 5-10 mug/day, or castration, reduces the progressive decline of plasma prothrombin-proconvertin seen in nonsupplemented intact male rats. The response of castrate females differs little from the response of intact females. Ethynylestradiol, 5-10 mug/day, affects both castrate males and females similarly, limiting the prothrombin-proconvertin decrease to about 13% below control value after 14 days. Intestinal absorption of vitamin K1 measured in the thoracic duct lymph of pentobarbital-anesthetized castrate male and female rats was shown to increase significantly after estrogen treatment. Estrogen-treated castrate male and female rats absorbed 25.8 mug and 11.8 mug vitamin K1, respectively. Nontreated control castrate male and female rats absorbed 0.0 mug and 1.2 mug, respectively, during a 240-min collection period. Use of radioactive vitamin K1 in similar experiments confirmed these results. Estrogen-treated castrate males absorbed vitamin K1 at the rate of 30-40 mug/g lymph whereas nontreated control males absorbed only about 6 mug/g lymph.

Topics: Animals; Castration; Dose-Response Relationship, Drug; Estrogens; Ethinyl Estradiol; Factor VII; Female; Hypoprothrombinemias; Intestinal Mucosa; Lymph; Male; Prothrombin; Rats; Vitamin K; Vitamin K Deficiency

Topics: Animals; Blood Coagulation; Cattle; Glutamates; Humans; Liver; Prothrombin; Rats; Vitamin K; Vitamin K Deficiency

Topics: Animals; Carboxy-Lyases; Male; Microsomes, Liver; Oligopeptides; Peptide Fragments; Prothrombin; Rats; Vitamin K; Vitamin K Deficiency

Topics: Animals; Ethers, Cyclic; Female; Fetus; Kidney; Liver; Male; Oxidoreductases; Oxygenases; Placenta; Pregnancy; Rats; Spleen; Vitamin K; Vitamin K Deficiency

Topics: Blood Coagulation Disorders; Diarrhea, Infantile; Female; Humans; Infant; Malabsorption Syndromes; Purpura; Vitamin K; Vitamin K Deficiency

Topics: Animals; Cytochrome P-450 Enzyme System; Cytosol; Kinetics; Liver; Male; Mass Spectrometry; Microsomes, Liver; Mixed Function Oxygenases; Prothrombin; Rats; Vitamin K; Vitamin K Deficiency; Warfarin

Vitamin K participates in the post-translational carboxylation of peptide-bound glutamate to form the gamma-carboxy-glutamate residues of prothrombin. The reaction requires reduced vitamin K, bicarbonate, oxygen, and a membrane-bound carboxylase. The active species of "CO2," i.e. CO2 or HCO3-, utilized in this carboxylation was determined by the low temperature method of Filmer and Cooper ((1970) J. Theor. Biol. 29, 131-145), taking advantage of the fact that menaquinone-2, in contrast to phylloquinone, is very active at 10 degrees. Microsomes from livers of vitamin K-deficient rats, were incubated in the presence of cycloheximide, avidin, NADH, menaquinone-2, 1 mM acetazolamide (to inhibit carbonic anhydrase), and either 14CO2 or H14CO3-. At 1-min intervals aliquots were removed from the reaction mixture. gamma-Carboxyglutamate was isolated from these samples by ion exchange chromatography after alkaline hydrolysis. After 1 min the incorporation of 14CO2 into gamma-carboxyglutamate was 8 to 10 times as great as that found with H14CO3-. When the carbonic anhydrase inhibitor was omited (with or without addition of exogenous carbonic anhydrase) the two incorporation curves approximated each other at a rate near that exhibited by bicarbonate alone. Similar results were obtained in a microsomal carboxylase system solubilized with Triton X-100. It is concluded that CO2 is the active species of "CO2" initially participating in the vitamin K-dependent carboxylation of preprothrombin and that neither ATP nor biotin is required for the reaction.

Topics: Animals; Bicarbonates; Carbon Dioxide; Carboxy-Lyases; Glutamates; Kinetics; Male; Membranes; Microsomes, Liver; Protein Precursors; Prothrombin; Rats; Vitamin K; Vitamin K Deficiency

The vitamin K-dependent carboxylating system has been solubilized by Lubrol PX or Triton X-100 treatment of vitamin K-deficient rat liver microsomes. As obtained from vitamin K-deficient rat liver, this soluble preparation is dependent upon the in vitro addition of vitamin K1 for carboxylating activity. The enzyme system is complex and is dependent upon NADH and dithiothreitol for maximum activity. While detergents used to solubilize the enzyme complex do markedly inhibit the activity of the system, the solubilized system is still highly responsive to vitamin K addition and can be used for further study of the carboxylating enzyme system. The requirement for dithiothreitol and the inhibition by p-hydroxymercuribenzoate indicate the involvement of an --SH enzyme in the carboxylating system.

Topics: Animals; Carboxy-Lyases; Cytosol; Detergents; Dithiothreitol; Hydrogen-Ion Concentration; Hydroxymercuribenzoates; Immunodiffusion; Kinetics; Liver; Microsomes, Liver; NAD; Rats; Solubility; Vitamin K; Vitamin K Deficiency

Vitamin K is required in an enzymatic reaction which carboxylates glutamyl residues in a microsomal protein precursor of plasma prothrombin to form gamma-carboxyglutamic acid residues. The partial requirements of this microsomal, vitamin K-dependent carboxylase system have been determined. A requirement of the system for cytosolic factors appears to be due primarily to the presence of reduced pyridine nucleotides or a reduced pyridine nucleotide-generating system in the cytosol. The hydroquinone of vitamin K has been demonstrated to be the enzymatically active form of the vitamin. When vitamin K1 hydroquinone is added to the carboxylase system, no NAD(P)H is needed for maximum activity. The carboxylase activity is half-maximally stimulated by 0.25 mug of vitamin K1/ml in the presence of cytosolic components but requires at least 10 times as much vitamin when microsomes are incubated in a cytosol-free buffer. Menadione is inactive as a vitamin source in this system, and the carboxylase activity is inhibited by the 2-chloro analog of vitamin K1 and by Warfarin. The ATP analog, AMP-P(NH)P, inhibited the carboxylase activity, but a dependence on exogenous ATP or an ATP-generating system could not be demonstrated. Carboxylase activity was found to be dependent on an O2-containing gas phase, and upon the HCO3- concentration.

Topics: Animals; Bicarbonates; Carbon-Carbon Ligases; Cytosol; Glutamates; Kinetics; Ligases; Liver; Magnesium; Male; Microsomes, Liver; NAD; Oxygen Consumption; Prothrombin; Rats; Vitamin K; Vitamin K Deficiency

Topics: Anaerobiosis; Animals; Carboxy-Lyases; Dithiothreitol; Hydroquinones; Kinetics; Microsomes, Liver; NAD; Proteins; Quinones; Rats; Vitamin K; Vitamin K Deficiency

Secondary vitamin K deficiency in rats caused by pelentan was accompanied by a decrease in the total collagen content and a rise in free oxyproline in the skin. Under these conditions the rate of collagen hydrolysis proved to increase. Vitamin K (vikasol) prevented development of the mentioned shifts in collagen metabolism.

Topics: Animals; Collagen; Ethyl Biscoumacetate; Hydroxyproline; Rats; Skin; Vitamin K; Vitamin K Deficiency

Rat liver microsomes contain a vitamin K-dependent carboxylase activity that converts specific glutamyl residues of microsomal prothrombin precursor to gamma-carboxyglutamic acid residues. This activity has now been solubilized by treatment with Triton X-100. The pentapeptide, Phe-Leu-Glu-Glu-Val, has been synthesized; and it has been demonstrated that, in the presence of this peptide, the solubilized microsomes catalyze a vitamin K-dependent incorporation of added H14CO3- into a low molecular weight trichloroacetic acid-soluble compound. The carboxylated product has been identified as peptide-bound gamma-carboxyglutamic acid by its chemical stability during acidic and alkaline hydrolysis and by co-chromatography of an alkaline hydrolysate of the product with authentic gamma-carboxyglutamic acid. The conditions for peptide carboxylation appear to be identical with those demonstrated for precursor carboxylation.

Topics: Animals; Carboxy-Lyases; Kinetics; Male; Microsomes, Liver; Oligopeptides; Rats; Vitamin K; Vitamin K Deficiency

Vitamin K is required for an enzymatic carboxylation of glutamyl residues in a microsomal protein precursor of plasma prothrombin to form gamma-carboxyglutamic acid. The enzyme system (carboxylase) which catalyzes this reaction has now been solubilized by extraction of the microsomes with Triton X-100 and has been shown to fix H14CO3- as gamma-carboxyglutamic acid residues in biologically active prothrombin. Enzyme activity requires O2 and vitamin K hydroquinone or vitamin K + NADH. Unlike the microsomal-bound carboxylase, soluble carboxylase activity is independent of either ATP or Mg2+ addition and is unaffected by either the ATP analog, adenyl-5'-yl imidodiphosphate (AMP-P(NH)P, or EDTA. These observations suggest that the energy required to drive the carboxylation reaction is derived from the oxidation of the reduced form of vitamin K. Although the membrane-bound carboxylase is inhibited by Warfarin, this anticoagulant is ineffective as an inhibitor of the soluble enzyme. A second anticoagulant, 2-chloro-3-phytyl-1,4-natpthoquinone (chloro-K), differs from Warfarin in that it effectively inhibits both the membrane-bound and soluble carboxylases.

Topics: Adenosine Triphosphate; Animals; Carboxy-Lyases; Enzyme Activation; Kinetics; Liver; Magnesium; Oxygen Consumption; Polyethylene Glycols; Prothrombin; Rats; Solubility; Vitamin K; Vitamin K Deficiency; Warfarin

This article gives a survey of the physiology of blood coagulation in newborn infants, subdivided into the particularities of the plasmic coagulation system and the fibronolysis. Etiology, diagnosis and therapy of the consumption coagulopathy as well as the coagulopathy of production are dealed with.

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Disseminated Intravascular Coagulation; Female; Fibrinolysis; Hemorrhagic Disorders; Heparin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Liver Diseases; Microcirculation; Plasma Substitutes; Prednisolone; Pregnancy; Streptokinase; Vitamin K; Vitamin K Deficiency

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Chronic Disease; Diarrhea, Infantile; Female; Gastrointestinal Hemorrhage; Hemorrhagic Disorders; Humans; Infant; Infant, Newborn; Malabsorption Syndromes; Male; Maternal-Fetal Exchange; Pregnancy; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

The incorporation of 14C-glucosamine and 3H-leucine into PIVKA-X and factor X has been studied in Macaca mulatta by means of a monospecific precipitating antiserum. No difference in the incorporation into PIVKA-X and factor X was found. The half-lives of PIVKA-X and factor X were similar (about 30-35 h and 27-31 h respectively) indicating that the vitamin K-induced modifications did not alter the survival of protein. A Russell's-viper venom/cephalin test system for factor X was more sensitive to inhibition by PIVKA-X than was a tissue thromboplastin-based system.

Topics: Adsorption; Animals; Barium Sulfate; Drug Stability; Factor X; Glucosamine; Half-Life; Haplorhini; Leucine; Macaca mulatta; Phosphatidylethanolamines; Protein Precursors; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Adult; Anemia, Macrocytic; Animals; Child; Cholestasis; Humans; Hypoprothrombinemias; Infant; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Malabsorption Syndromes; Male; Protein-Energy Malnutrition; Vitamin E; Vitamin E Deficiency; Vitamin K; Vitamin K Deficiency

Topics: Asphyxia Neonatorum; Autoantibodies; Blood Coagulation Tests; Blood Platelets; Blood Transfusion; Capillary Fragility; Capillary Permeability; Cerebral Hemorrhage; Disseminated Intravascular Coagulation; Exchange Transfusion, Whole Blood; Female; Hemophilia A; Hemorrhage; Hemorrhagic Disorders; Heparin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Lung; Maternal-Fetal Exchange; Pregnancy; Thrombocytopenia; Vitamin K; Vitamin K Deficiency; von Willebrand Diseases

Topics: Acetates; Animals; Female; Fetal Death; Hemorrhage; Hydroquinones; Infertility, Female; Male; Pregnancy; Pregnancy Complications; Rats; Vitamin E; Vitamin E Deficiency; Vitamin K; Vitamin K Deficiency

The bovine plasma zymogen prothrombin contains a number of gamma-carboxyglutamic acid residues which are not found in an abnormal prothrombin produced when cattle are given the vitamin K antagonist dicoumarol. These modified glutamic acid residues appear to be formed post-translationally by a reaction which requires vitamin K. It has been shown that postmitochondrial supernates from vitamin K-deficient rats incorporate added H-14-CO3- minus into microsomal proteins upon the addition of vitamin K. This incorporation is dependent upon the presence of the prothrombin precursor in the microsomal preparations, and upon factors which are present in the postmicrosomal supernatant. Most of the radioactive protein which can be obtained from the microsomal pellet by extraction with 0.25% Triton X-100 has been identified as prothrombin and it can be shown that all of the radioactivity is in the amino-terminal activation fragment of prothrombin. This portion of the protein has previously been shown to contain the gamma-carboxyglutamic acid residues. Hydrolysis of the purified radioactive prothrombin resulted in a loss of 50% of the radioactivity and subsequent chromatography of the amino acid hydrolyzate demonstrated that the remaining radioactivity was entirely in glutamic acid. These results are consistent with the hypothesis that all of the H-14-CO3- minus was incorporated into the carboxyl groups of gamma-carboxyglutamic acid residues.

Topics: Animals; Bicarbonates; Carbon Radioisotopes; Cattle; Cytosol; Liver; Male; Prothrombin; Rats; Vitamin K; Vitamin K Deficiency; Warfarin

Two-week-old chicks adequate in vitamin K showed a relative lack of vitamin K-dependent clotting factors when compared with the rat, cow, and man. Chick prothrombin was 50%, IX 8%, and X 6% of respective levels in the rat. Factor VII was not detectable in chick plasma. When 1-day-old chicks were fed a vitamin K-deficient diet, prothrombin levels fell to 5% in 5 days, whereas factors IX and X fell to only 60% of normal. After warfarin administration to normal chicks, prothrombin levels fell to 20% in 6 hours, whereas factors IX and X fell to 60%. When cycloheximide was given to normal chicks, all vitamin K-dependent factors fell at the same relative rate with a half time of 2 hours. Cycloheximide also completely blocked the effect of physiological doses (10 mug) of phylloquinone upon prothrombin synthesis, but only partially blocked the effect of pharmacological doses (2.5 mg) of phylloquinone, suggesting an antagonism between cycloheximide and vitamin K at the ribosomal level. Puromycin was effective in blocking the action of vitamin K at both physiological and pharmacological doses. In the chick, unlike the rat, it appears that (1) cycloheximide is fully effective in blocking the action of physiological doses of vitamin K and (2) the regulatory systems for factors IX and X appear to have a higher affinity for vitamin K and a lower affinity for warfarin than the regulatory system for prothrombin.

Topics: Animals; Blood Coagulation Tests; Chickens; Cycloheximide; Dactinomycin; Factor IX; Factor X; Protein Biosynthesis; Prothrombin; Puromycin; Species Specificity; Time Factors; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Warfarin

A dietary deficiency of vitamin K has been demonstrated in the Syrian hamster. This species has also been shown to be relatively resistant to the action of the indirect anticoagulant Warfarin, and very sensitive to the anticoagulant action of the vitamin K antagonist chloro-K. These observations, and the hamster's apparently high requirement for the vitamin, indicate that it responds to vitamin K and vitamin K antagonists in the same fashion as Warfarin-resistant strains of rats.

Topics: Animals; Anticoagulants; Blood Coagulation; Cricetinae; Diterpenes; Drug Tolerance; Male; Naphthoquinones; Prothrombin; Species Specificity; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Warfarin

The oxidation of phylloquinone to the 2,3-epoxide (by phylloquinone epoxidase) was studied in liver from control and warfarin-resistant rats. The reaction requires microsomal fraction, soluble protein, a heat-stable soluble factor and O(2). It is not inhibited by CO or CN(-). Epoxidase activity was stimulated if plasma prothrombin was lowered either by anticoagulants or the absence of vitamin K. The activity of the enzyme rapidly returned to normal values after the administration of vitamin K to hypoprothrombinaemic rats. These differences in the activity of the enzyme occur in the microsomal fraction and not the cytosol. A thrombin-generating polypeptide that accumulates in microsomal fraction of hypothrombinaemic rats correlated directly with epoxidase activity. These data support the view that enzymic interconversion of phylloquinone and its 2,3-epoxide participates in the biological activity of vitamin K.

Topics: Animals; Anticoagulants; Blood Coagulation; Carbon Monoxide; Cyanides; Drug Resistance; Edetic Acid; Epoxy Compounds; Female; Flavin-Adenine Dinucleotide; Hypoprothrombinemias; Kinetics; Male; Microsomes, Liver; NAD; NADP; Oxidoreductases; Oxygenases; Proteins; Prothrombin; Rats; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Warfarin

Topics: Amino Acids; Aminopeptidases; Animals; Bicarbonates; Carbon Dioxide; Carbon Radioisotopes; Chromatography, Ion Exchange; Electrophoresis, Disc; Glutamates; Hydrogen-Ion Concentration; Kinetics; Peptide Fragments; Pronase; Prothrombin; Rats; Time Factors; Trypsin; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Animals; Antimetabolites; Cycloheximide; Kinetics; Liver; Magnesium; Male; Potassium; Prothrombin; Rats; Subcellular Fractions; Time Factors; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Animals; Blood Coagulation; Body Weight; Carotenoids; Chickens; Fibrinogen; Liver; Prothrombin Time; Time Factors; Vitamin A; Vitamin K; Vitamin K Deficiency

Topics: Biopsy, Needle; Blood Coagulation Disorders; Hemorrhagic Disorders; Hepatitis; Humans; Hypoprothrombinemias; Infant; Infusions, Parenteral; Iron; Liver Function Tests; Malabsorption Syndromes; Male; Prothrombin Time; Thromboplastin; Vitamin K; Vitamin K Deficiency

Topics: Animals; Carbon Radioisotopes; Epoxy Compounds; Half-Life; Liver; Male; Proadifen; Prothrombin; Rats; Tritium; Vitamin K; Vitamin K Deficiency; Warfarin

After reviewing the available methods for the clinical study of the extrinsec way of the coagulative process (Quick's time, Owren's Thrombotest and Normotest), the AA. explain what is the significance that the most of hte researchers ascribe to time-value discrepancies between Thrombotest and Normotest. The AA. remember that while the former is sensitive to the presence of certain inhibitors called PIVKA (Protein Induced by Vitamin K Absence or Antagonists), just as Quick's original time; the latter is on the contrary insensitive to them. Then it provides more significant data about the real rate of factors II, VII, and X. Such inhibitors have been found also in subjects that did not undergo any anti-vitamin K therapy and peculiarly in cases in which a Intravascular Coagulation occurred. Therefore the AA. thought to verify the hypothesis that the detection of a discrepancy between TT and NT could be useful in the clinical diagnosis of I.C. which is a serious and often hardly detectable disorder of haemostasis. The AA. have therefore tested 72 patients, 65 of which showed the evidence of I.C. and 7 with I.C. probabilities. The discrepancy values that were obtained are showed in Table I. The first group (65 cases) was furtherly divided into four subgroups, according to the positivities obtained from SDPS test, as shown in Table II. The AA. can therefore come to the following conclusions: a) In human Intravascular Coagulation, the discrepancy between NT/TT may occur with a frequency of 57 per cent but it is not a constant event. b) The discrepancy rate is generally of low degree, being of high degree only in twelve cases (18.5 per cent. c) Analyzing the discrepancy presence and rate in relation to the number of SDPS test positivities, we can notice that the values are remarkably scattered and it is not possible, only on the basis of these data to make a statistical evaluation of their significativity because the groups are not comparable among them, being in exc3ss the cases in which paracoagulation occurs in a low degree. We can only state that the absence of discrepancy predominates in the cases in which a low number of positivities of SDPS test occurs, and on the contrary the discrepancy is a constant event in the cases in which SDPS test shows a large number of positivities. In consitive test to detect Intravascular Coagulation, but we think the positivity of this test may be a support in doubtful cases.

Topics: Blood Coagulation Tests; Blood Proteins; Disseminated Intravascular Coagulation; Humans; Prothrombin Time; Vitamin K; Vitamin K Deficiency

Topics: Anti-Arrhythmia Agents; Anticoagulants; Antihypertensive Agents; Diuretics; Drug Interactions; Drug Tolerance; Heart Failure; Humans; Hypolipidemic Agents; Intestinal Absorption; Tolbutamide; Vitamin K; Vitamin K Deficiency

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Clofibrate; Hemorrhage; Humans; Male; Methods; Middle Aged; Prothrombin Time; Pulmonary Embolism; Sodium; Vitamin E; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Escherichia coli Infections; Factor IX; Factor VII; Factor X; Female; Gastroenteritis; Heparin; Humans; Infant; Infant, Newborn; Liver Diseases; Male; Prothrombin; Sepsis; Vitamin K; Vitamin K Deficiency

Topics: Aflatoxins; Animal Feed; Animals; Avitaminosis; Calcium; Chickens; Diet; Male; Poultry Diseases; Riboflavin; Riboflavin Deficiency; Thiamine; Thiamine Deficiency; Vitamin D; Vitamin D Deficiency; Vitamin E; Vitamin E Deficiency; Vitamin K; Vitamin K Deficiency

Topics: Animals; Anticoagulants; Coumarins; Ethers, Cyclic; Hypoprothrombinemias; Male; Microsomes, Liver; Prothrombin; Rats; Structure-Activity Relationship; Tritium; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Warfarin

Topics: Albinism; Animals; Blood Coagulation Tests; Chromosome Mapping; Crosses, Genetic; Drug Resistance; Female; Genotype; Heterozygote; Homozygote; Liver; Male; NADH, NADPH Oxidoreductases; Quinones; Rats; Recombination, Genetic; Time Factors; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Anti-Bacterial Agents; Blood Coagulation Tests; Diagnosis, Differential; Disseminated Intravascular Coagulation; Factor V; Factor VIII; Fibrinogen; Heparin; Humans; Infant, Newborn; Infant, Premature, Diseases; Male; Parenteral Nutrition; Prothrombin Time; Thromboplastin; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Animals; Blood Coagulation Tests; Chromatography, DEAE-Cellulose; Electrophoresis, Disc; Hirudins; Hypoprothrombinemias; Immunodiffusion; Liver; Male; Microsomes, Liver; Protein Precursors; Prothrombin; Rabbits; Rats; Snakes; Spectrophotometry, Ultraviolet; Thrombin; Time Factors; Venoms; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Animals; Blood Coagulation Tests; Drug Resistance; Female; Homozygote; Hybridization, Genetic; Hypoprothrombinemias; Injections, Subcutaneous; Male; Nutritional Requirements; Rats; Rodent Diseases; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Blood Coagulation Tests; Blood Platelets; Disseminated Intravascular Coagulation; Factor V Deficiency; Factor VIII; Fibrinogen; Heparin; Humans; Liver Diseases; Prothrombin Time; Thromboplastin; Vitamin K; Vitamin K Deficiency

Topics: Animals; Chlorine; Drug Resistance; Female; Hypoprothrombinemias; Male; Naphthoquinones; Prothrombin; Rats; Rats, Inbred Strains; Sex Factors; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Adult; Blood Coagulation Tests; Blood Group Incompatibility; Exchange Transfusion, Whole Blood; Female; Histocompatibility; Histocompatibility Antigens; Humans; Immunity, Cellular; Infant, Newborn; Infant, Newborn, Diseases; Male; Maternal-Fetal Exchange; Pedigree; Pregnancy; Thrombocytopenia; Vitamin K; Vitamin K Deficiency

Topics: Adult; Factor V Deficiency; Female; Humans; Infant, Newborn; Male; Pregnancy; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Adult; Aged; Anticoagulants; Blood Coagulation Disorders; Female; Heparin; Humans; Intestinal Absorption; Male; Middle Aged; Vitamin K; Vitamin K Deficiency

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Coagulation Factors; Blood Platelet Disorders; Blood Platelets; Dicumarol; Factor VII; Glycine max; Hemorrhage; Hemostatics; Humans; Pedigree; Phospholipids; Plasma; Prothrombin; Prothrombin Time; Rabbits; Thrombocytopenia; Thromboplastin; Vitamin K; Vitamin K Deficiency

Topics: Animals; Cycloheximide; Dactinomycin; Dicumarol; Factor V; Fructose-Bisphosphate Aldolase; Kynurenine; L-Serine Dehydratase; Liver; Male; Phenprocoumon; Prothrombin; Rats; Tryptophan Oxygenase; Vitamin K; Vitamin K Deficiency

Massive subaponeurotic haematoma occurred in a baby after suture of bleeding scalp blood sampling stabs made before delivery. Eighteen hours after delivery blood samples showed marked prolongation of the prothrombin time. The condition was successfully treated with vitamin K(1) and blood transfusion.

Topics: Acute Disease; Adult; Blood Specimen Collection; Blood Transfusion; Female; Fetus; Hematoma, Epidural, Cranial; Hemorrhage; Humans; Infant, Newborn; Labor, Obstetric; Male; Pregnancy; Prothrombin Time; Punctures; Scalp; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Diet; Female; Humans; Infant, Newborn; Intestinal Absorption; Nutritional Physiological Phenomena; Nutritional Requirements; Pregnancy; Vitamin K; Vitamin K Deficiency

Topics: Animals; Binding Sites; Biological Assay; Cell Nucleus; Isomerism; Kidney; Liver; Male; Microsomes, Liver; Mitochondria, Liver; Muscles; Myocardium; Prothrombin; Rats; Ribosomes; Time Factors; Tritium; Vitamin K; Vitamin K 1; Vitamin K Deficiency

Topics: Adsorption; Animals; Barium Sulfate; Cycloheximide; Electrophoresis, Disc; Kinetics; Male; Microsomes, Liver; Prothrombin; Prothrombin Time; Rats; Vibration; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Animal Nutritional Physiological Phenomena; Animals; Carbon Isotopes; Cell-Free System; Coumarins; Dactinomycin; In Vitro Techniques; Iodine Isotopes; Male; Microsomes, Liver; Peptide Chain Elongation, Translational; Peptide Chain Initiation, Translational; Prothrombin; Radioimmunoassay; Rats; Time Factors; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Biliary Fistula; Colonic Diseases; Feces; Humans; Intestinal Fistula; Lipid Metabolism; Malabsorption Syndromes; Male; Middle Aged; Postoperative Complications; Vitamin K; Vitamin K Deficiency

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Child; Child, Preschool; Diagnosis, Differential; Disseminated Intravascular Coagulation; Hemolytic-Uremic Syndrome; Hemostasis; Heparin; Humans; Kidney Diseases; Liver Diseases; Protease Inhibitors; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Blood Coagulation Factors; Cystic Fibrosis; Diarrhea, Infantile; Diet; Humans; Hypoprothrombinemias; Infant; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Cystic Fibrosis; Diet; Female; Hemoglobins; Hemorrhagic Disorders; Humans; Hypoprothrombinemias; Infant; Malabsorption Syndromes; Male; Prothrombin Time; Vitamin K; Vitamin K Deficiency

Topics: Adult; Aged; Anti-Bacterial Agents; Hemorrhage; Humans; Hypoprothrombinemias; Intensive Care Units; Liver; Long-Term Care; Male; Middle Aged; Time Factors; Vitamin K; Vitamin K Deficiency

Topics: Animals; Anticoagulants; Blood Coagulation Tests; Factor IX; Factor VII; Factor X; Hemorrhagic Disorders; Humans; Methods; Prothrombin; Rabbits; Thromboembolism; Vitamin K; Vitamin K Deficiency

Topics: Hemorrhage; Humans; Infant, Newborn; Infant, Newborn, Diseases; Milk, Human; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Animals; Breast Feeding; Humans; Hypoprothrombinemias; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Newborn, Diseases; Milk; Milk, Human; Prospective Studies; Prothrombin Time; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Animals; Caseins; Diet Therapy; Food; Humans; Infant; Infant Food; Infant Nutrition Disorders; Infant Nutritional Physiological Phenomena; Malabsorption Syndromes; Meat; Milk; Nutritional Requirements; Vitamin K; Vitamin K Deficiency

Topics: Adult; Animals; Drug Resistance; Female; Humans; Hypoprothrombinemias; Male; Middle Aged; Prothrombin Time; Rats; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Child; Child, Preschool; Humans; Kidney Diseases; Vitamin K; Vitamin K Deficiency

Previous studies have shown that the vitamin K-induced synthesis of prothrombin in a vitamin K-deficient rat is only slightly inhibited by cycloheximide treatment. Rat prothrombin has now been purified by disc electrophoresis after BaSO(4) adsorption and citrate elution. When cycloheximide (5 mg/kg) was given to vitamin K-deficient rats 30 min before vitamin K, about 70% of the amount of prothrombin seen in rats not treated with cycloheximide was produced (two-stage assay), and the prothrombin band could be seen on the electrophoretic gels. However, if radioactive amino acids are administered to the rats after cycloheximide treatment, the newly formed prothrombin contains no radioactivity. The isolated prothrombin does contain radioactivity if the vitamin K-deficient rats are treated with vitamin K but no cycloheximide. When radioactive amino acids were given to deficient rats 1 hr before cycloheximide and vitamin K, radioactivity was found in prothrombin. These data suggest that, in the intact rat, the action of vitamin K is to convert a protein precursor with a short biological half life to prothrombin.

Topics: Amino Acids; Animals; Barium Sulfate; Carbon Isotopes; Chemical Precipitation; Cycloheximide; Diet; Electrophoresis, Disc; Enzyme Precursors; Male; Metabolism; Prothrombin; Rats; Time Factors; Tritium; Vitamin K; Vitamin K Deficiency

Topics: Age Factors; Australia; Blood Coagulation Tests; Humans; Infant; Surgical Procedures, Operative; Vitamin K; Vitamin K Deficiency

Topics: Amino Acids; Animals; Barium Sulfate; Blood Proteins; Carbon Isotopes; Electrophoresis, Disc; Glucosamine; Male; Mannose; Metabolism; Prothrombin; Rats; Tritium; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Male; Muscles; Phosphorus; Rats; Skin; Vitamin E; Vitamin K; Vitamin K Deficiency

Topics: Animals; Chickens; Female; Intestinal Absorption; Male; Poultry Diseases; Prothrombin Time; Triglycerides; Vitamin K; Vitamin K Deficiency

Topics: Alkylation; Animals; Chickens; Chromatography, Gas; Chromatography, Thin Layer; Farnesol; Microsomes, Liver; Mitochondria, Liver; Phosphoric Acids; Quinones; Rats; Terpenes; Tritium; Vitamin K; Vitamin K Deficiency

Topics: Animals; Blood Proteins; Cycloheximide; Enzyme Induction; Hydrocortisone; Male; Metabolism; Prothrombin; Rats; Time Factors; Tyrosine Transaminase; Vitamin K; Vitamin K 1; Vitamin K Deficiency

Topics: Canada; Denmark; History, 20th Century; United States; Vitamin K; Vitamin K Deficiency

Topics: Age Factors; Aged; Anemia; Anti-Bacterial Agents; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Tests; Ecchymosis; Female; Hematuria; Humans; Liver Diseases; Malabsorption Syndromes; Male; Middle Aged; Vitamin K; Vitamin K Deficiency

Topics: Adsorption; Amino Acids; Animals; Barium Sulfate; Carbon Isotopes; Male; Prothrombin; Rats; Tritium; Vitamin K; Vitamin K 1; Vitamin K Deficiency

Topics: Binding Sites; Blood Coagulation; Blood Coagulation Factors; Coumarins; Drug Antagonism; Drug Synergism; Enzyme Induction; Humans; Molecular Biology; Protein Binding; Prothrombin Time; Vitamin K; Vitamin K Deficiency

Topics: Female; Hemorrhage; Humans; Hypoprothrombinemias; Infant; Vitamin K; Vitamin K Deficiency

Topics: Animals; Carbon Isotopes; Male; Oxides; Prothrombin; Rats; Time Factors; Tritium; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Warfarin

Topics: Administration, Oral; Adolescent; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Child; Child, Preschool; Cyanosis; Factor V; Factor VII; Heart Defects, Congenital; Humans; Injections, Intramuscular; Prothrombin; Prothrombin Time; Vitamin K; Vitamin K Deficiency

Topics: Animals; Creatine Kinase; Ethyl Biscoumacetate; Male; Muscles; Rats; Vitamin E; Vitamin K; Vitamin K Deficiency

Topics: Birth Injuries; Birth Weight; Craniocerebral Trauma; Female; Hematoma; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Injections, Intramuscular; Male; Punctures; Sex Factors; Vitamin K; Vitamin K Deficiency

Topics: Alcohols; Animals; Chromatography; Chromatography, Thin Layer; Dicumarol; Digestive System; Kidney; Liver; Male; Myocardium; Quinones; Rats; Tritium; Vitamin K; Vitamin K Deficiency

Topics: Age Factors; Bilirubin; Blood Coagulation; Blood Glucose; Blood Proteins; Blood Transfusion; Carbohydrate Metabolism; Carcinoma, Hepatocellular; Child; Female; Hepatectomy; Humans; Hyperbilirubinemia; Infant; Infusions, Parenteral; Liver Neoplasms; Male; Postoperative Care; Postoperative Complications; Prothrombin Time; Serum Albumin; Vitamin K; Vitamin K Deficiency

Topics: Anemia, Neonatal; Blood Transfusion; Exchange Transfusion, Whole Blood; Factor VII; Factor X; Female; Hematocrit; Humans; Infant, Newborn; Infant, Newborn, Diseases; Liver Diseases; Male; Prothrombin; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Animals; Blood Coagulation Factors; Cycloheximide; Factor IX; Factor VII; Factor VIII; Factor X; Liver; Male; Methods; Oxygen Consumption; Puromycin; Rats; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Animals; Blood Coagulation Tests; Cycloheximide; Dactinomycin; Depression, Chemical; Liver; Male; Metabolism; Naphthoquinones; Protein Biosynthesis; Prothrombin; Rats; RNA; Stimulation, Chemical; Time Factors; Tritium; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Warfarin

Topics: Amino Acids; Animal Nutritional Physiological Phenomena; Animals; Antimetabolites; Ascorbic Acid; Cysteine; Diet; Dietary Fats; Ethers; Fats; Genetics; Hypoprothrombinemias; Linoleic Acids; Male; Phosphates; Prothrombin Time; Rats; Solubility; Species Specificity; Stimulation, Chemical; Vitamin A; Vitamin E; Vitamin K; Vitamin K Deficiency; Water

Coumarin anticoagulants inhibit the release of plasma clotting factor VII by vitamin K in liver slices from vitamin K-deficient animals without inhibition of protein synthesis. When the ratio of vitamin K to coumarin anticoagulant is kept constant, but the concentrations are increased, the inhibition disappears. This suggests that the pharmacological action of coumarin anticoagulants depends on irreversible inhibition of normal vitamin K transport to its site of action. At higher concentrations of vitamin K the inhibition can be surmounted, because vitamin K can enter the cell by an alternate route that is not inhibited by coumarin anticoagulants.

Topics: Animals; Anticoagulants; Biological Transport; Carbon Isotopes; Coumarins; Depression, Chemical; Factor VII; In Vitro Techniques; Leucine; Liver; Protein Biosynthesis; Rats; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Warfarin

Topics: Animals; Cell Nucleus; Feces; Injections, Intraperitoneal; Lipids; Liver; Male; Microsomes; Mitochondria, Liver; Phosphates; Prothrombin; Prothrombin Time; Rats; Ribosomes; Solubility; Surface-Active Agents; Tritium; Vitamin K; Vitamin K Deficiency; Water

Topics: Cell Division; Melatonin; Pineal Gland; Plasmodium; Serotonin; Ubiquinone; Vitamin E Deficiency; Vitamin K; Vitamin K Deficiency

Topics: Animals; Cell Nucleus; Centrifugation; Chromatography; Detergents; Endoplasmic Reticulum; Liver; Microsomes; Mitochondria, Liver; Naphthoquinones; Prothrombin; Rats; Ribosomes; Solubility; Spleen; Time Factors; Tritium; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Warfarin

Topics: Amino Acids; Animals; Carbon Isotopes; Cycloheximide; Dactinomycin; Dicumarol; Liver; Male; Microsomes; Mitochondria, Liver; Protein Biosynthesis; Prothrombin; Prothrombin Time; Puromycin; Rats; Time Factors; Ultrasonics; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Animals; Biological Assay; Injections; Male; Prothrombin; Quinones; Rats; Vitamin K; Vitamin K Deficiency

Topics: Animals; Female; Microscopy, Electron; Pituitary Gland; Rats; Vitamin K; Vitamin K Deficiency

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Humans; Vitamin K; Vitamin K Deficiency

Topics: Animals; Biological Assay; Blood Coagulation; Radiation Effects; Rats; Solutions; Spectrophotometry; Vitamin K; Vitamin K Deficiency

Topics: Animals; Chickens; Dactinomycin; Liver; Phosphorus Isotopes; Prothrombin; Puromycin; RNA; RNA, Transfer; Vitamin K; Vitamin K Deficiency

Topics: Animals; Birds; Chickens; Kidney; Mammals; Rats; Vitamin K; Vitamin K Deficiency

Topics: Animals; Hot Temperature; Poultry Diseases; Prothrombin Time; Stress, Physiological; Vitamin K; Vitamin K Deficiency

Topics: Animals; Female; Male; Mineral Oil; Quinones; Rats; Sex; Squalene; Vitamin A; Vitamin K; Vitamin K Deficiency

Topics: Animals; Blood Coagulation; Male; Prothrombin; Quinones; Rats; Squalene; Vitamin A; Vitamin K; Vitamin K Deficiency

Topics: Blood Coagulation Factors; Humans; Prothrombin Time; Starvation; Vitamin K; Vitamin K Deficiency

Topics: Animals; Coumarins; Factor VII; Naphthoquinones; Rats; Vitamin K; Vitamin K Deficiency

Topics: Animals; Blood Coagulation Tests; Breast Feeding; Circumcision, Male; Factor VII; Factor X; Hematocrit; Humans; Hypoprothrombinemias; Infant, Newborn; Milk; Prothrombin; Prothrombin Time; Social Conditions; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Blood Transfusion; Factor VII; Fibrinogen; Fibrinolysis; Humans; Immunosuppressive Agents; Steroids; Vitamin K; Vitamin K Deficiency

A haemorrhagic diathesis is described in infants; this is preceded and accompanied by constitutional symptoms such as fever, diarrhoea, vomiting, anorexia, and pallor. These children had a severe coagulation abnormality, due to deficiency of vitamin-K-dependent coagulation factors, and it was corrected by administration of vitamin K. No conclusion could be drawn as to the aetiology of this condition but some possible causes are discussed.

Topics: Blood Coagulation Factors; Blood Coagulation Tests; Blood Transfusion; Female; Hemorrhagic Disorders; Humans; Infant; Male; Vitamin K; Vitamin K Deficiency

Topics: Animals; Chickens; Diet; Poultry Diseases; Vitamin K; Vitamin K Deficiency

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Humans; Propylthiouracil; Prothrombin; Salicylates; Vitamin K; Vitamin K Deficiency

Topics: Antifibrinolytic Agents; Aprotinin; Blood Coagulation Disorders; Blood Coagulation Factors; Fibrinolysis; Humans; Thrombin; Uremia; Vitamin K; Vitamin K Deficiency

Topics: Blood Coagulation Tests; Hematoma; Hemophilia A; Hemorrhagic Disorders; Humans; Infant, Newborn; Infant, Newborn, Diseases; Injections, Intramuscular; Male; Vitamin K; Vitamin K Deficiency

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Capillary Permeability; Drug Therapy; Factor V; Factor VII; Fibrinogen; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Prothrombin Time; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Animals; Animals, Newborn; Dog Diseases; Dogs; Drug Therapy; Pathology; Vitamin K; Vitamin K Deficiency

Topics: Adult; Aged; Blood Coagulation Factors; Diagnosis, Differential; Dicumarol; Female; Humans; Injections, Intravenous; Male; Malingering; Middle Aged; Prothrombin Time; Vitamin K; Vitamin K Deficiency

Topics: Animals; Dactinomycin; Dicumarol; DNA; Enzyme Repression; Genetic Code; Liver; Models, Theoretical; Molecular Biology; Poultry; Prothrombin; RNA; Vitamin K; Vitamin K Deficiency

Topics: Blood Coagulation Disorders; Child, Preschool; Female; Humans; Rocky Mountain Spotted Fever; Thrombocytopenia; Vitamin K; Vitamin K Deficiency

Topics: Animals; Germ-Free Life; Rats; Vitamin A; Vitamin K; Vitamin K Deficiency

Actinomycin D inhibits vitamin K induced formation of prothrombin in chicks deficient in vitamin K. The administration of actinomycin in doses which inhibit prothrombin formation also inhibits synthesis in the liver of RNA from adenosine triphosphate as detected with adenine-8-C1(4). The results are consistent with a genetic action of vitamin K in inducing RNA formation for the synthesis of clotting proteins

Topics: Adenine; Adenine Nucleotides; Adenosine Triphosphate; Animals; Antimetabolites; Carbon Isotopes; Dactinomycin; Liver; Metabolism; Naphthoquinones; Pharmacology; Poultry; Proteins; Prothrombin; Prothrombin Time; Research; RNA; Vitamin K; Vitamin K Deficiency

Topics: Alanine Transaminase; Aspartate Aminotransferases; Bilirubin; Blood; Blood Coagulation Factors; Child; D-Alanine Transaminase; Epidemiology; Hepatitis; Hepatitis A; Humans; Liver Function Tests; Vitamin K; Vitamin K Deficiency

Topics: Animals; Diet; Food Irradiation; Haplorhini; Macaca mulatta; Meat; Neomycin; Nutritional Status; Oxytetracycline; Pharmacology; Prothrombin Time; Research; Vitamin K; Vitamin K Deficiency

Topics: Antifibrinolytic Agents; Estradiol; Estrogens; Humans; Prothrombin Time; Retinoids; Testosterone; Vitamin K; Vitamin K Deficiency

Topics: Biochemical Phenomena; Biochemistry; Blood Coagulation Factors; Blood Coagulation Tests; Dicumarol; Enzyme Precursors; Factor IX; Factor VII; Factor X; Humans; Hypoprothrombinemias; Liver Diseases; Liver Function Tests; Prothrombin; Vitamin K; Vitamin K Deficiency

Topics: Animals; Arachis; Escherichia coli; Fats; Germ-Free Life; Ginsenosides; Intestines; Oils; Rats; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Vitamins

Topics: Animals; Diet; Female; Rats; Vitamin K; Vitamin K Deficiency

Topics: Antifibrinolytic Agents; Humans; Naphthoquinones; Retinoids; Vitamin K; Vitamin K 1; Vitamin K Deficiency

Topics: Antifibrinolytic Agents; Hemorrhagic Disorders; Humans; Naphthoquinones; Pregnancy; Pregnancy Complications; Vitamin K; Vitamin K Deficiency

Topics: Antifibrinolytic Agents; Celiac Disease; Hemorrhagic Disorders; Humans; Sprue, Tropical; Steatorrhea; Vitamin K; Vitamin K Deficiency

Topics: Antifibrinolytic Agents; Factor IX; Factor VII; Factor X; Hemorrhagic Disorders; Hemostatics; Humans; Prothrombin; Steatorrhea; Vitamin K; Vitamin K Deficiency

Topics: Animals; Metabolism; Rats; Retinoids; Vitamin K; Vitamin K Deficiency

Topics: Dicumarol; Humans; Liver; Vitamin K; Vitamin K Deficiency

Topics: Anticoagulants; Cell Respiration; Coumarins; Cytochromes c; Liver; NAD; Oxidoreductases; Vitamin K; Vitamin K Deficiency

Topics: Animals; Antifibrinolytic Agents; Chickens; Naphthoquinones; Vitamin K; Vitamin K 1; Vitamin K 3; Vitamin K Deficiency

Topics: Animals; Antifibrinolytic Agents; Chickens; Hemostatics; Vitamin K; Vitamin K 1; Vitamin K 3; Vitamin K Deficiency

Topics: Antifibrinolytic Agents; Coumarins; Dicumarol; Humans; Hypoprothrombinemias; Vitamin K; Vitamin K Deficiency

Topics: Dicumarol; Humans; Phenindione; Vitamin K; Vitamin K Deficiency

Topics: Humans; Neoplasms; Vitamin K; Vitamin K Deficiency

Topics: Animals; Antifibrinolytic Agents; Biliary Tract; Cholestasis; Heparin Antagonists; Humans; Male; Rabbits; Vitamin K; Vitamin K Deficiency

Topics: Antifibrinolytic Agents; Blood; Blood Coagulation Disorders; Dicumarol; Heparin Antagonists; Humans; Vitamin K; Vitamin K Deficiency

Topics: Dicumarol; Humans; Prothrombin; Vitamin A; Vitamin K; Vitamin K Deficiency

Topics: Dicumarol; Humans; Prothrombin; Vitamin K; Vitamin K Deficiency

Topics: Animals; Chickens; Humans; Lipids; Liver; Vitamin K; Vitamin K Deficiency; Vitamins

Topics: Antifibrinolytic Agents; Humans; Naphthoquinones; Retinoids; Vitamin K; Vitamin K Deficiency; Vitamins