vitamin-k-semiquinone-radical and Blood-Coagulation-Disorders

Rare bleeding disorders (RBDs), including factor (F) I, FII, FV, FVII, combined FV and FVIII (CF5F8), FXI, FXIII and vitamin-K dependent coagulation factors (VKCF) deficiencies, are a heterogeneous group of hemorrhagic disorder with a variable bleeding tendency. RBDs are due to mutation in underlying coagulation factors genes, except for CF5F8 and VKCF deficiencies. FVII deficiency is the most common RBD with >330 variants in the F7 gene, while only 63 variants have been identified in the F2 gene. Most detected variants in the affected genes are missense (>50% of all RBDs), while large deletions are the rarest, having been reported in FVII, FX, FXI and FXIII deficiencies. Most were located in the catalytic and activated domains of FXI, FX, FXIII and prothrombin deficiencies. Understanding the proper molecular basis of RBDs not only can help achieve a timely and cost-effective diagnosis, but also can help to phenotype properties of the disorders.

Topics: Blood Coagulation Disorders; Blood Coagulation Disorders, Inherited; Blood Coagulation Factors; Coagulation Protein Disorders; Hemorrhage; Hemorrhagic Disorders; Humans; Vitamin K

Long-term anticoagulation is used worldwide to prevent or treat thrombotic events. Anticoagulant therapy using vitamin K antagonists (VKAs) is well established; however, anticoagulants carry an increased risk of potentially life-threatening bleeding. In cases of bleeding or need for surgery, patients require careful management, balancing the need for rapid anticoagulant reversal with risk of thromboembolic events. Prothrombin complex concentrates (PCCs) replenish clotting factors and reverse VKA-associated coagulopathy. Two forms of PCC, 3-factor (3F-PCC) and 4-factor (4F-PCC), are available. Using PRISMA methodology, we systematically reviewed whether 4F-PCC is superior to 3F-PCC for the reversal of VKA-associated coagulopathy. Of the 392 articles identified, 48 full texts were reviewed, with 11 articles identified using criteria based on the PICOS format. Data were captured from 1,155 patients: 3F-PCC,

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Factor IX; Fibrinolytic Agents; Hemorrhage; Humans; International Normalized Ratio; Retrospective Studies; Thromboembolism; Vitamin K

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

Anticoagulant and antiplatelet therapy have become increasingly popular. The goal of therapy is to prevent venous thromboembolism and platelet aggregation, respectively. Traditional anticoagulant and antiplatelet drugs are quickly being replaced with novel medications with more predictable pharmacokinetics. Unfortunately, these drugs carry the risk of uncontrolled hemorrhage because of drug-induced coagulopathy. Uncontrolled hemorrhage continues to be a major cause of preventable death: hemorrhage accounts for approximately 30% of trauma-related deaths, second to brain injury. Controlling hemorrhage while dealing with comorbidities remains a challenge to clinicians. There are many gaps in care and knowledge that contribute to the struggle of treating this patient population.. This literature review is focused on the most effective ways to achieve hemostasis in a patient with drug-induced coagulopathy. The antiplatelet therapies aspirin, clopidogrel, ticlopidine, pasugrel, and ticagrelor are analyzed. Anticoagulant therapies are also reviewed, including warfarin, rivaroxaban, apixaban, edoxaban, and dabigatran. In addition, viscoelastic testing and platelet function assays are reviewed for their ability to monitor drug effectiveness and to accurately depict the patient's ability to clot. This review focuses on articles from the past 10 years. However, there are limitations to the 10-year restriction, including no new research posted within the 10-year timeline on particular subjects. The most recent article was then used where current literature did not exist (within 10 years).. Traditional anticoagulants have unpredictable pharmacokinetics and can be difficult to correct in bleeding emergencies. Vitamin K has been proven to reliably and effectively reverse the effect of vitamin K antagonists (VKAs) while having a lower anaphylactoid risk than frozen plasma. Prothrombin complex concentrates should be used when there is risk of loss of life or limb. Frozen plasma is not recommended as a first-line treatment for the reversal of VKAs. Novel anticoagulants have specific reversal agents such as idarucizumab for dabigatran and andexxa alfa for factor Xa (FXa) inhibitors. Although reliable, these drugs carry a large price tag. As with traditional anticoagulants, cheaper alternative therapies are available such as prothrombin complex concentrates. Finally, static coagulation testing works well for routine therapeutic drug monitoring but may not be appropriate during bleeding emergencies. Viscoelastic testing such as thromboelastography and rotational thromboelastometry depict in vivo hemostatic properties more accurately than static coagulation assays. Adding viscoelastic testing into resuscitation protocols may guide blood product usage more efficiently.. This review is intended to be used as a guide. The topics covered in this review should be used as a reference for treating the conditions described. This review article also covers laboratory testing and is meant as a guide for physicians on best practices. These findings illustrate recommended testing and reversal techniques based off evidence-based medicine and literature.

Topics: Anticoagulants; Blood Coagulation Disorders; Dabigatran; Emergencies; Hemorrhage; Humans; Vitamin K

Patients who had mechanical heart valves and an international normalized ratio (INR) of >5.0 should be managed by temporary cessation of vitamin K antagonist. This study aimed to investigate the safety of low-dose vitamin K1 in patients with mechanical heart valves who have supratherapeutic INR.. CINAHL, Cochran Library, Clinical trial.gov, OpenGrey, PubMed, ScienceDirect, and Scopus were systematically searched from the inception up to October 2021 without language restriction. Studies comparing the safety of low-dose vitamin K1 treatment in patients with placebo or other anticoagulant reversal agents were included. We used a random-effect model for the meta-analysis. Publication bias was determined by a funnel plot with subsequent Begg's test and Egger's test.. From 7529 retrieved studies, 3 randomized control trials were included in the meta-analysis. Pooled data demonstrated that low-dose vitamin K was not associated with thromboembolism rate (risk ratio [RR] = 0.94; 95% CI: 0.19-4.55) major bleeding rate (RR = 0.58; 95% CI: 0.07-4.82), and minor bleeding rate (RR = 0.60; 95% CI: 0.07-5.09). Subgroup and sensitivity analysis demonstrated the nonsignificant effect of low-dose vitamin K on the risk of thromboembolism. Publication bias was not apparent, according to Begg's test and Egger's test (P = .090 and 0.134, respectively).. The current evidence does not support the role of low-dose vitamin K as a trigger of thromboembolism in supratherapeutic INR patients with mechanical heart valves. Nevertheless, more well-designed studies with larger sample sizes are required to justify this research question.

Topics: Blood Coagulation Disorders; Heart Valves; Humans; International Normalized Ratio; Thromboembolism; Vitamin K; Vitamin K 1; Vitamins

Physicians often come across with cases of vitamin K antagonists-dependent coagulopathy for reasons such as accidental use of the vitamin K antagonists (VKA), excessive administration of prescribed anticoagulants of indirect action or not reported administration of vitamin K antagonists due to memory impairment and/or other mental disorders, even deliberate use thereof (attempt to murder or suicide). Rodenticide-poisoning (coumarins, warfarins) via food or occupational accidents are difficult to diagnose. This article discusses different types of acquired vitamin K-dependent coagulopathy. Differential diagnosis is primarily based on patient statements before additional causes of vitamin K deficiency are explored. Even when pathological vitamin K deficiency is not determined, appropriate and urgent medical treatment is necessary: administration of fresh frozen plasma or concentrated factors of the prothrombin complex, administration of vitamin K remedies along with symptomatic therapy. With early diagnosis and prescription of appropriate therapy, prognosis is favorable. Reasons for vitamin K antagonists-dependent coagulopathy cases.

Topics: Anticoagulants; Blood Coagulation Disorders; Drug Overdose; Humans; Vitamin K

The vitamin K antagonists (VKAs) have been the standard (and only) oral anticoagulants used for the long-term treatment or prevention of venous thromboembolism or stroke in patients with atrial fibrillation. The coagulopathy induced by VKAs can be reversed with vitamin K, and in urgent situations, the vitamin K-dependent coagulation factors can be replaced by transfusion. In the last decade, a new class of oral anticoagulants has been developed, direct oral anticoagulants that bind to a specific coagulation factor and neutralize it. These compounds were shown to be effective and safe compared with the VKAs and were licensed for specific indications, but without a specific reversal agent. The absence of a reversal agent is a barrier to more widespread use of these agents. Currently, for the management of major life-threatening bleeding with the direct oral anticoagulants, most authorities recommend the use of four factor prothrombin complex concentrates. There are now three reversal agents in development and poised to enter the market. Idarucizumab is a specific antidote targeted to reverse the direct thrombin inhibitor, dabigatran, which was recently approved for use in the USA. Andexanet alfa is an antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor enoxaparin. Ciraparantag is an antidote targeted to reverse the direct thrombin and factor Xa inhibitors as well as the indirect inhibitor enoxaparin.

Topics: Administration, Oral; Animals; Antibodies, Monoclonal, Humanized; Anticoagulants; Antifibrinolytic Agents; Antithrombins; Arginine; Blood Coagulation Disorders; Blood Coagulation Factors; Coagulants; Combined Modality Therapy; Dabigatran; Drugs, Investigational; Enoxaparin; Factor Xa; Fibrinolytic Agents; Humans; Piperazines; Practice Guidelines as Topic; Recombinant Proteins; Vitamin K

The aim of the study was to summarize available literature regarding the interaction between vitamin K antagonists (VKAs) and trimethoprim-sulfamethoxazole (co-trimoxazole, TMP-SMX), and to provide recommendations for managing patient risk from this interaction. Data sources were English-language publications in the medical literature and Internet databases. Relevant publications that directly or indirectly addressed the VKA-TMP-SMX interaction were selected and reviewed. The mechanism of the VKA-TMP-SMX interaction, frequency of concurrent use, effect on international normalized ratio (INR), increased risk of bleeding, and strategies for risk reduction are summarized. The concurrent use of VKA and TMP/SMX rapidly and consistently raises INR and is associated with a two- to five-fold increase in bleeding. Concurrent use of VKA and TMP-SMX should be avoided when possible. When VKA and TMP-SMX are co-prescribed, VKA dose reduction is usually required. Patient education as well as early and frequent INR monitoring is recommended to reduce risk from this interaction.

Topics: Aged, 80 and over; Anti-Infective Agents; Anticoagulants; Blood Coagulation Disorders; Drug Interactions; Female; Humans; International Normalized Ratio; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination; Vitamin K; Warfarin

Although warfarin and heparin have been mainstays of anticoagulation for almost 50 years, the recent introduction of multiple oral anticoagulants has led some practitioners to shift away from warfarin as the anticoagulant of choice for various diseases. Major advances have been made in targeting downstream clotting factors in the coagulation cascade, resulting in two major new classes of drugs: direct thrombin inhibitors and factor Xa inhibitors. Developed partially with the patient in mind, these drugs are taken orally and, because of their target specificity, have eliminated the need for routine blood monitoring, making them attractive to patients currently on warfarin.

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Hemorrhage; Humans; Platelet Aggregation Inhibitors; United States; Vitamin K

Coagulopathy after cardiac surgery with cardiopulmonary bypass is a serious complication that may result in massive bleeding requiring transfusion of significant amounts of blood products, plasma, and platelets. In addition to increased patient morbidity and mortality it is associated with longer hospital stay and increased resource utilization. The current review discusses aspects in cardiopulmonary bypass-induced coagulopathy with emphasis on point-of-care testing and individualized "goal-directed" therapy in patients who develop excessive bleeding after cardiac surgery.

Topics: Blood Coagulation Disorders; Blood Transfusion; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Factor VIIa; Fibrinogen; Humans; Point-of-Care Systems; Vitamin K

Bleeding is the second leading cause of death after trauma. Initial care of the patient with hemorrhage focuses on restoring circulating blood volume and reversing coagulopathy. Trauma and injury can initiate the coagulation cascade. Patients with massive bleeding should be resuscitated with goal-directed therapy. Hemostatic resuscitation in conjunction with ratio-based transfusion and massive transfusion protocols should be utilized while awaiting hemorrhage control. The military initiated massive transfusion protocols in the battlefield. We discuss the coagulation cascade, recent recommendations of goal-directed therapy, massive transfusion protocols, fixed ratios, and the future of transfusion medicine.

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Blood Transfusion; Clinical Protocols; Critical Illness; Hemorrhage; Humans; Hypothermia; Thrombelastography; Vitamin K

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Fibrinolytic Agents; Hemostatics; Humans; Intracranial Hemorrhages; Intraoperative Period; Perioperative Care; Platelet Aggregation Inhibitors; Preoperative Care; Vitamin K

Vitamin-K antagonists (VKA) are the current standard for oral anticoagulation. However, they carry several problems in older patients: frequent bleeding complications, complex management, risk of interactions with multiple drugs. Two new classes of oral anticoagulants (NOA) are now available: direct thrombin inhibitors (dabigatran); and direct factor Xa inhibitors (rivaroxaban, apixaban) and others. Their management is easier: quickly effective after administration, they are given at fixed doses and do not need regular laboratory monitoring. Several randomized trials have shown that NOA are non-inferior to heparins and VKA for treating venous thromboembolic disease (prophylactic or curative treatment) and atrial fibrillation (prevention of associated embolisms). NOA are also being studied for long-term treatment after acute coronary syndromes. Data regarding older people is still sparse. No trial has specifically studied older patients. In the context of atrial fibrillation, subgroup analysis show similar results between patients above and below 75 years old, except for dabigatran which seems to carry more bleeding complications in people older than 75 years, specially with the highest dose employed. All NOA are eliminated at least partly by kidneys. Their dose must be reduced in moderate renal failure (filtration glomerular rate (FGR) 30 to 50 ml/min) and they are contra-indicated in severe renal failure (FGR<30 ml/min). Doses of dabigatran and apixaban should be reduced in older people too. NOA also have other unresolved problems: drug interactions are still possible, specific coagulation test to assess them must be developed, and no specific antidote is currently available in case of hemorrhagic complication.

Topics: 4-Hydroxycoumarins; Administration, Oral; Age of Onset; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Disorders; Hematology; Humans; Indenes; Risk Assessment; Vitamin K

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Component Transfusion; Factor VIIa; Female; Humans; Male; Monitoring, Physiologic; Plasma; Risk Assessment; Severity of Illness Index; Treatment Outcome; Vitamin K; Warfarin

As chronic kidney disease (CKD) is a contraindication to the use of the new anticoagulants, the vitamin K antagonists (VKA) are still valid in patients with CKD, though their use may be harmful. During overanticoagulation, some patients can develop acute kidney injury (AKI), especially those with CKD, by obstruction of the renal tubules and Bowman's spaces by erythrocytes. In addition, VKA increase atherogenesis through vitamin K deficiency, which is essential for the carboxylation of proteins that inhibit calcification of vessels. Eventually, hemodialysed patients under VKA have an increased risk of stroke, especially those over 75 years of age. Therefore anticoagulation with VKA in patients with CKD should be carefully implemented and its monitoring more frequent than in non-CKD patients.

Topics: 4-Hydroxycoumarins; Acute Kidney Injury; Anticoagulants; Atherosclerosis; Blood Coagulation Disorders; Cerebrovascular Disorders; Coumarins; Humans; Indenes; Renal Insufficiency, Chronic; Vitamin K; Warfarin

Dabigatran etexilate is emerging as an alternative for vitamin K antagonists, but evidence-based guidelines for management of intracerebral hemorrhage and acute ischemic stroke in patients taking this drug are nonexistent. This review summarizes current knowledge on key pharmacological features and the assessment of dabigatran activity. Pragmatic approaches are provided for individualized decision taking with regard to hemostatic therapy and reperfusion strategies in acute stroke patients.

Topics: Anticoagulants; Benzimidazoles; Blood Coagulation Disorders; Case Management; Cerebral Hemorrhage; Cerebral Infarction; Dabigatran; Guidelines as Topic; Hemostasis; Hemostatics; Humans; Off-Label Use; Pyridines; Renal Dialysis; Reperfusion; Stroke; Vitamin K

Anticoagulant drugs are taken by millions of patients throughout the world. Warfarin has been the most widely prescribed anticoagulant for decades. In recent years, new oral anticoagulants have been approved for use, are being positioned as alternatives to warfarin, and represent an enormous market opportunity for pharmaceutical companies. Requests for urgent reversal of anticoagulants are not uncommon especially in the setting of critical bleeding. This review summarizes information on reversal of warfarin by vitamin K, plasma, prothrombin complex concentrates, and recombinant VIIa. In addition, we emphasize the lack of current evidence supporting reversibility of the new oral direct thrombin inhibitors and Factor Xa inhibitors. This review is presented to assist transfusion medicine specialists, hematologists, and other clinicians who prescribe blood components for reversal of drug-induced anticoagulation.

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Component Transfusion; Hematology; Hemorrhage; Humans; Models, Biological; Plasma; Vitamin K; Warfarin

Anticoagulant therapy, including conventional agents and a variety of new oral, fast-acting drugs, is prescribed for millions of patients annually. Each anticoagulant varies in its effect on routine and specialty coagulation assays and each drug may require distinct laboratory assay(s) to measure drug concentration or activity. This review provides an overview of the assorted assays that can measure anticoagulant drug concentration or activity and includes key assay interferences. The effect of these conventional and new anticoagulant agents on specialty coagulation assays used to evaluate for bleeding or clotting disorders, and whether this impact is physiological or factitious, is included. Also provided is a short review of superwarfarin poisoning and features distinguishing this from warfarin overdose. Knowledge of clinically significant pearls and pitfalls pertinent to coagulation assays in relation to anticoagulant therapy are important to optimize patient care.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Drug Monitoring; Factor Xa Inhibitors; Hematology; Hemostasis; Humans; Thrombin; Vitamin K; Warfarin

The continuing education course "Hemostasis" provided a comprehensive review of hemostasis and selected perturbations of the underlying processes as well as an assessment of hemostasis in animal models and preclinical testing environments. The session began with a review of the current state of understanding of hemostasis and how the waterfall or cascade of activation has transformed to the current cell-based, membrane-associated sequence of highly regulated events. The specific mechanisms of drug-induced thrombocytopenia were then presented, followed by a discussion of the relationships of coagulation and platelets in inflammation and cancer metastasis and platelet activity. Evaluation of hemostasis and platelet function in animals and especially in the environment of the contract research facility concluded the session.

Topics: Animals; Blood Coagulation; Blood Coagulation Disorders; Blood Platelets; Education, Continuing; Hemostasis; Humans; Inflammation; Models, Animal; Neoplasm Metastasis; Platelet Activation; Platelet Aggregation; Thrombocytopenia; Vitamin K

Intracerebral hemorrhage in patients with warfarin-associated coagulopathy is an increasingly common life-threatening condition that requires emergent management. The evolution of therapeutic options in this setting, as well as recently published guidelines, has resulted in some heterogeneity in recommendations by professional societies. This heterogeneity can be attributed to lack of evidence-based support for plasma therapy; the variability in availability of prothrombin complex concentrates; the variability in the coagulation factor levels and contents of prothrombin complex concentrates; ambiguity about the optimal dose and route of administration of vitamin K; and the lack of standardized clinical care pathways, particularly in community hospitals, for the management of these critical care patients. In this review, we summarize the relevant literature about these controversies and present recommendations for management of patients with warfarin-associated coagulopathy and intracerebral hemorrhage.

Topics: Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; Cerebral Hemorrhage; Female; Humans; Male; Vitamin K; Warfarin

This review describes some natural proteins, which can be employed, either as factor concentrates derived from human plasma or as recombinant drug, to modulate the coagulation system. I will address some biochemical characteristics and the physiological role of von Willebrand factor, the coagulation factors of the extrinsic and intrinsic pathways, and the physiological anticoagulant protein C. In addition, I will detail the pharmacological compounds, which are available for influencing or substituting the coagulation proteins: desmopressin (DDAVP), single coagulation factor concentrates, prothrombin complex concentrates, and protein C concentrate. In particular, I will address some treatment topics of general medical interest, such as the treatment of massive bleeding, the correction of the coagulopathy induced by vitamin K-antagonists in patients with cerebral haemorrhage, and of the coagulopathy of meningococcemia. Finally, I will describe some properties and practical clinical applications of the recombinant anticoagulans lepirudin and bivalirudin, which are derived from hirudin, the natural anticoagulant of the medical leech.

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Proteins; Cerebral Hemorrhage; Hemorrhage; Hirudins; Humans; Peptide Fragments; Protein C; Recombinant Proteins; Vitamin K; von Willebrand Factor

Warfarin is the most common form of oral anticoagulant therapy. Although it has indisputable benefit in the management of thromboembolic disease, warfarin-associated coagulopathy (WAC) is a well-documented complication of its use. As warfarin exerts its effect by impairing formation of the vitamin K-dependent clotting factors, a cornerstone of WAC management is vitamin K replacement. Daily vitamin K supplementation is an emerging approach to regulate international normalized ratios in difficult-to-control patients. Mild WAC without bleeding can often be managed with warfarin withdrawal alone. For excessive international normalized ratio elevation in the absence of bleeding, low-dose oral vitamin K (1?2.5 mg) is sufficient and achieves the same degree of international normalized ratio correction by 24 h as intravenous therapy. The stable patient with WAC and minor bleeding can also be given oral vitamin K, with correction of the underlying defect. Major bleeding should first be managed with factor replacement for immediate correction of the coagulopathy, using either a prothrombin complex concentrate or fresh-frozen plasma. High-dose vitamin K (10 mg) should be given concurrently via intravenous infusion to confer lasting correction. Warfarin resistance and vitamin K-associated anaphylaxis are rare. Despite development of new oral anticoagulant therapy compounds, warfarin will probably retain a prominent role in thromboembolism management for several years to come.

Topics: Blood Coagulation Disorders; Humans; International Normalized Ratio; Vitamin K; Warfarin

Numerous risk factors for instability of oral anticoagulation have been identified, including variability in vitamin K intake. However, few studies have directly tested the feasibility of manipulating dietary vitamin K to achieve stable oral anticoagulation. Recent findings from a randomized clinical trial suggest that dietary vitamin K manipulation is a viable option for managing stability of oral anticoagulant therapy. The approach appears to be effective for those patients who are under-anticoagulated and consume a small number of vitamin K-rich food sources. While an encouraging option for management of warfarin therapy, longer-term studies in different patient populations are required.

Topics: Anticoagulants; Blood Coagulation Disorders; Drug Stability; Humans; Randomized Controlled Trials as Topic; Vitamin K; Warfarin

Recombinant activated factor VII (rFVIIa) is a haemostatic agent, which was originally developed for the treatment of haemophilia patients with inhibitors against factor FVIII or FIX. The efficacy of rFVIIa in preventing or stopping life-threatening bleeding for these patients has been demonstrated in several studies. Since the first report about the successful use of rFVIIa in a bleeding soldier in 1999, rFVIIa has gained popularity as an adjunct for the treatment of coagulopathy in a wide array of clinical conditions with serious or life-threatening bleeding. The number of case reports and case series documenting the successful use of rFVIIa as last resort to terminate uncontrollable bleeding has steadily grown. Conflicting results have been reported from various studies. Considering the lack of data and potential publication bias associated with case reports, this review summarises the clinical evidence of the efficacy and safety of rFVIIa in the perioperative period.

Topics: Animals; Blood Coagulation Disorders; Factor VIIa; Hemostatics; Humans; Monitoring, Intraoperative; Perioperative Care; Recombinant Proteins; Vitamin K

Disorders of coagulation are common adverse drug events encountered in critically ill patients and present a serious concern for intensive care unit (ICU) clinicians. Dosing strategies for medications used in the ICU are typically developed for use in noncritically ill patients and, therefore, do not account for the altered pharmacokinetic and pharmacodynamic properties encountered in the critically ill as well as the increased potential for drug-drug interactions, given the far greater number of medications ordered. This substantially increases the risk for coagulation-related adverse reactions, such as a bleeding or prothrombotic events. Although many medications used in the ICU have the potential to cause coagulation disorders, the exact incidence will vary based on the specific medication, dose, concomitant drug therapy, ICU setting, and patient-specific comorbidities. Clinicians must strongly consider these factors when evaluating the risk/benefit ratio for a particular therapy. This review surveys recent literature documenting the risk for adverse drug reactions specific to bleeding and/or clotting with commonly used medications in the ICU.

Topics: Anti-Infective Agents; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Coagulation Factors; Colloids; Critical Care; Deamino Arginine Vasopressin; Drug-Related Side Effects and Adverse Reactions; Erythropoietin; Estrogens, Conjugated (USP); Factor VIIa; Fibrinolytic Agents; Fondaparinux; Hemostatics; Humans; Polysaccharides; Protein C; Recombinant Proteins; Thrombin; Thromboembolism; Vitamin K

Because of the firm refusal of transfusion of blood and blood components by Jehovah's Witnesses, the management of Jehovah's Witness patients with severe bleeding is often complicated by medical, ethical, and legal concerns. Because of a rapidly growing and worldwide membership, physicians working in hospitals should be prepared to manage these patients. Appropriate management of a Jehovah's Witness patient with severe bleeding entails understanding of the legal and ethical issues involved, and meticulous medical management, including treatment of hypovolemic shock, local hemostatic interventions, and administration of prohemostatic agents, when appropriate. In addition, high-dose recombinant erythropoietin in combination with supplemental iron may enhance the speed of hemoglobin synthesis.

Topics: Acute Disease; Adult; Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Transfusion; Contraindications; Emergencies; Erythropoietin; Hemorrhage; Hemostatic Techniques; Humans; Informed Consent; Jehovah's Witnesses; Phlebotomy; Recombinant Proteins; Shock; Treatment Refusal; Unconsciousness; Vitamin K

Protein Z (PZ) is a vitamin K-dependent factor identified in human plasma in 1984 characterized by an homology with other vitamin K-dependent factors (factor VII, IX, X, protein C). In contrast to these factors, PZ does not possess any enzymatic activity but is involved as a cofactor in the down-regulation of coagulation by forming a complex with the protein Z-dependent protease inhibitor (ZPI). ZPI inhibits the activated factor X (FXa) on phospholipid surface. In mice, the disruption of PZ gene is asymptomatic, but the association with the factor V Leiden mutation leads to a quasi complete mortality during the neonatal period with microvascular thrombosis. In humans, PZ is characterized by an unusual wide distribution in plasma, and a major decrease induced by warfarin. Isolated PZ deficiency does not seem to constitute a risk for venous thrombosis, but a severe PZ deficiency could increase the risk of well recognized venous thrombotic risk factors such as factor V Leiden, G20210A mutation or hyperhomocysteinemia. Unexpectedly, a relationship between PZ deficiency and ischemic arterial diseases such as stroke, acute coronary syndromes or peripheral arterial disease was described but not confirmed by all studies. PZ deficiency could be also a risk factor for early fetal losses, and increases the arterial risk in antiphospholipid syndrome. This review analyzes the different studies so far published and discusses the various results obtained in order to understand whether or not protein Z deficiency could be considered as an arterial ischemic risk factor.

Topics: Animals; Blood Coagulation Disorders; Blood Proteins; Female; Humans; Pregnancy; Pregnancy Complications, Hematologic; Vitamin K

Congenital bleeding disorders of the vitamin K-dependent coagulation factors represent only about 15-20% of all congenital bleeding disorders. However, they played an important role of the history of blood coagulation. Prothrombin was the first entity dealt with. Subsequently, in the late 1940s or early 1950s, the discovery of factor IX allowed the separation of hemophilia into two groups, A and B. In the 1950s, the discovery of factors VII and X allowed the formulation of a logic and plausible explanation for the clotting mechanism. The subsequent discovery of vitamin K-dependent proteins with an inhibitory effect on blood coagulation has further enhanced the importance of the vitamin K-dependent clotting factors. Recently, the study of families with multiple defects of the prothrombin complex has spurred the interest in vitamin K metabolism and the gamma-carboxylation system. The relevance of these studies had also an important role in the understanding the mechanism of action of other noncoagulation-related proteins. The vitamin K-dependent clotting factors represent a homeostatic mechanism at the basis of the hypercoagulability (thrombosis)-hypocoagulability (hemorrhagic) system, namely, to a mechanism that is vital for survival. The different bleeding condition will be dealt with separately, namely, prothrombin or Factor II, Factor VII, Factor IX (hemophilia B), and Factor X deficiencies. An additional heading deals with the combined defect of the prothrombin complex, namely, combined deficiency of Factor II, Factor VII, Factor IX, and Factor X. Since, sometimes, a hemorrhagic role has been attributed to Protein Z deficiency, another vitamin K-dependent protein, this defect will also be dealt with, even though briefly. Each deficiency has been approached in a global manner, namely, with adequate reference to history, background, prevalence, classification, hereditary pattern, biochemistry and function, molecular biology, clinical picture, updated laboratory diagnosis, prognosis, and therapy. Particular emphasis has been placed on the significance of cases with "true" deficiency [cross-reacting material (CRM negative)] and cases with abnormalities (CRM positive). The genetic, clinical, and laboratory implications of these two forms have been extensively discussed in every instance. The importance of a multiple, combined diagnostic approach that has to include whenever possible clotting, chromogenic, immunological, and molecular biology studies has bee

Topics: Blood Coagulation Disorders; Blood Proteins; Factor VII Deficiency; Factor X Deficiency; Hemophilia B; Humans; Hypoprothrombinemias; Prognosis; Vitamin K

The hemostatic system in its multiple components displays an intricate organization in time which is characterized by circadian (approximately 24-hour), circaseptan (approximately 7-day), menstrual (approximately monthly), and circannual (approximately yearly) bioperiodicities. The interaction of the rhythms of the variables participating in hemostasis determine transient risk states of thromboembolic events, including myocardial infarction and stroke, and of hemorrhage and hemorrhagic events, each with a unique timing. The circadian staging of the rhythms in vascular, cellular, and coagulation factors that favors blood coagulation and thrombosis coincides with the daily minimum in fibrinolytic activity; as a result there is elevated risk in the morning of acute myocardial infarction and stroke. Similar hemostatic rhythms may determine the epidemiology of thromboembolic and hemorrhagic events during the week, month and year. This article focuses on the large-amplitude circadian rhythms operative in the hemostatic system. Their implication for preventive and curative pharmacotherapy of hemostatic disorders is presented, with discussion of related problems.

Topics: Autonomic Nervous System; Blood Coagulation; Blood Coagulation Disorders; Chronobiology Phenomena; Circadian Rhythm; Female; Fibrinolysis; Hemostasis; Heparin; Humans; Menstrual Cycle; Platelet Aggregation Inhibitors; Platelet Count; Thrombolytic Therapy; Thrombosis; Vitamin K

Topics: Anti-Inflammatory Agents, Non-Steroidal; Blood Coagulation Disorders; Blood Coagulation Factors; Fibrinolytic Agents; Hemorrhage; Heparin; Humans; Platelet Aggregation Inhibitors; Time Factors; Vitamin K

An excessive anticoagulant effect because of coumarins is frequently encountered.. To review available literature on the management of warfarin-associated coagulopathy and to propose evidence-based treatment algorithms.. Data sources were Medline and Embase. Papers published between 1966 and December 2005 describing randomized trials or prospective cohort studies evaluating treatments for coumarin-associated coagulopathy were abstracted.. Low dose oral vitamin K rapidly and reliably returns the international normalized ratio (INR) to the usual therapeutic range in non-bleeding patients. Simple withholding of acenocumarol results in rapid correction of its anticoagulant effect. The impact of oral vitamin K on phenprocumon-associated coagulopathy cannot be determined from available literature. Intravenous vitamin K and coagulation factors should be given to patients with major or life-threatening hemorrhage. The optimal dose and type of coagulation factor is not known.. Vitamin K therapy is an effective treatment for INR prolongation in patients with coumarin-associated coagulopathy; coagulation factor replacement is required, in addition, in patients with major bleeding or with indication for immediate correction of their INR. Clinical trials powered to detect differences in rates of bleeding and thrombosis are now required to determine if vitamin K reduces the risk of bleeding without causing thrombosis in non-bleeding patients with prolonged INR.

Topics: Algorithms; Biological Factors; Blood Coagulation Disorders; Coumarins; Hemorrhage; Humans; Vitamin K

Topics: Antifibrinolytic Agents; Blood Coagulation Disorders; Hospitalization; Humans; International Normalized Ratio; Vitamin K

Topics: Animals; Anticoagulants; Blood Coagulation Disorders; Humans; Vitamin K

Excessive anticoagulation is a frequent complication of anticoagulant therapy. The risk of hemorrhage approximately doubles for each one point increase in the International Normalized Ratio (INR) above 3.0. Reducing a prolonged INR to within the desired therapeutic range requires that oral anticoagulants be withheld. In addition, vitamin K may be administered. Since this latter treatment can produce rapid reductions in the INR, it must be carefully tailored to meet individual needs, balancing the risk of bleeding against the potential risk of causing thromboembolism.. To review available literature on the management of coumarin-associated coagulopathy in asymptomatic patients, a Medline search was carried out and papers published in English from 1966 and 2003 were identified. All available information on the management of asymptomatic patients presenting with coumarin-associated coagulopathy was analyzed.. Following the results of clinical studies that only used an elevated INR as a surrogate end-point for the risk of bleeding, low dose oral vitamin K appears as the preferable strategy for rapidly restoring therapeutic INR levels in asymptomatic patients who present with an excessively prolonged INR due to warfarin therapy. For the treatment of patients with asymptomatic acenocoumarol-induced coagulopathy, vitamin K does not add any benefit to the strategy of simply withholding oral anticoagulant treatment.. Large randomized trials using clinical end-points are now required to provide evidence-based treatment recommendations for patients with coumarin-associated coagulopathy.

Topics: Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; Costs and Cost Analysis; Coumarins; Hemorrhage; Humans; International Normalized Ratio; Risk Factors; Vitamin K; Warfarin; Withholding Treatment

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

For more than 60 years, vitamin K-dependent proteins have been known to play an important role in regulating blood coagulation. During recent years it has become clear, however, that vitamin K is also involved in other physiologic processes, including bone metabolism and vascular biology. Because the vitamin K requirement of bone and vessel wall is higher than that of the liver (where the clotting factors are produced) recommended daily allowance (RDA) values for K vitamins must be redefined. According to the new definition, a substantial part of the population is mildly deficient in vitamin K, and at later ages this deficiency may contribute to increased bone fracture risk, arterial calcification, and cardiovascular disease.

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Vessels; Bone and Bones; Carboxy-Lyases; Food Analysis; Humans; Vitamin K

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

Treatment with coumarin oral anticoagulants, such as warfarin, is effective antithrombotic therapy, but patients treated with these drugs are at significant risk of bleeding. The risk of haemorrhage increases with increasing intensity of anticoagulation and overanticoagulation is common. Reversal can be achieved by stopping the coumarin drug or administration of vitamin K, fresh frozen plasma or coagulation factor concentrates. However, there are surprisingly few studies defining the optimum dose of these products and there are no randomized studies comparing the relative benefit and risk of coagulation factor concentrates versus fresh frozen plasma. Guidelines for the management of overdose are based on level III and IV evidence and are, therefore, only grade B recommendations at best. Further studies are required to determine the most effective use of products and the dose required for safe reversal of overanticoagulation.

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Drug Overdose; Hemorrhage; Humans; Plasma; Vitamin K; Warfarin

Topics: Bleeding Time; Blood Coagulation; Blood Coagulation Disorders; Clinical Laboratory Techniques; Disseminated Intravascular Coagulation; Fibrinolysis; Humans; Mass Screening; Partial Thromboplastin Time; Risk Factors; Thromboplastin; Transfusion Reaction; Vitamin K

Eighteen patients with an acute thrombosis of the splanchnic veins were reviewed. Most of apparently idiopathic cases of splanchnic vein thrombosis are related to an increased coagulation related to a congenital or acquired defect of haemostasis. The aim of this study was to assess the effects of a new and effective treatment. Nine male and 9 female patients (range of age: 19 to 81 years) experienced a mesenteric venous thrombosis. There were 14 mesenteric vein thromboses with infarction, two transient mesenteric venous ischaemias without bowel infarction and two acute thromboses of the splanchnic veins without bowel ischaemia. A coagulopathy was detected in seven patients: oral contraception, protein C (PC) or antithrombin III (AT III) congenital deficiencies, acquired deficiency of AT III, PC and protein S (PS), polycythaemia in the post-partum period and primary myeloproliferative disorder. No coagulopathy was associated with thrombosis in eight cases: mesenteric haematoma, splenomegaly, cirrhosis, appendicectomy, cholescytectomy, chronic heart failure, treatment with beta-adrenergic receptor antagonist and digitalis, stenosis of the portal anastomosis after liver transplantation. Twelve patients required surgery: eight intestinal bowel resections with immediate anastomosis, four resections without immediate anastomosis. Only one patient underwent a second look for a repeat bowel resection. No death occurred in the early postoperative period and 17 out of 18 patients were alive after 12 years. An oral anticoagulant therapy was undertaken from two months to seven years. However, three patients suffered a recurrent thrombosis. Two of them required a long-term anticoagulation. Six patients experienced a portal hypertension and oral anticoagulants were discontinued in three of them because of bleeding oesophageal varices. Six patients were treated only by unfractionated heparin (UFH) or low molecular weight heparin (LMWH) followed by oral anticoagulants. After laparotomy, two were only treated with UFH without any bowel resection, as mesenteric venous ischaemia was too extensive. These observations suggest that the choice between an appropriate medical or surgical treatment is important and must be discussed. Since 1989, the therapeutic choice has been modified by ultrasonography and contrast enhanced computed tomographic scan which confirms diagnosis, allows to follow up and check the effects of anticoagulation and to choose the time for surgery. When the

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antithrombin III; Blood Coagulation Disorders; Female; Humans; Male; Mesenteric Vascular Occlusion; Mesenteric Veins; Middle Aged; Protein C Deficiency; Protein S Deficiency; Risk Factors; Thrombosis; Vitamin K

Many new developments have taken place in the field of coagulation during the past year. We focus on the interesting new controversies surrounding vitamin K prophylaxis of the newborn infant, on the increasing information regarding the growth factors responsible for thrombopoiesis, and on the role of protein C in the genesis of thrombosis.

Topics: Bleeding Time; Blood Coagulation Disorders; Blood Platelets; Child; Hematopoietic Cell Growth Factors; Humans; Infant, Newborn; Protein C Deficiency; Vitamin K; Vitamin K Deficiency Bleeding

Genetically, Klinefelter's syndrome is characterized by a super-numerary chromosome X in male subjects presenting with clinical and biochemical hypoandrogenism and relative hyperoestrogenism. The association of Klinefelter's syndrome with chronic leg ulcer has given rise to numerous publications. The cause of the trophic disorders is unclear. We report two cases of this syndrome associated with chronic leg ulcers and anomalies of haemostasis. One of these two patients had platelet hyperaggregability followed by disorders of fibrinolysis, while the other had disorders of fibrinolysis. We reviewed the literature concerning the various aetiopathogenic hypotheses put forward to explain the cause of these leg ulcers, as well as their interactions and relationship with the hormonal anomalies. The position occupied by disorders of haemostasis is particularly developed.

Topics: Adult; Aspirin; Blood Coagulation Disorders; Gonadal Steroid Hormones; Humans; Klinefelter Syndrome; Leg Ulcer; Male; Platelet Aggregation; Vitamin K

The increased prevalence of rodents resistant to warfarin led to the development of the hydroxycoumarin anticoagulant brodifacoum. A 25-year-old man attempted suicide by consuming four boxes of d-CON Mouse-Prufe II; each box contains 42 g of bait that is 0.005% brodifacoum. He presented to a hospital nine days later with syncope, hematochezia, gross hematuria, epistaxis, anemia, and a severe coagulopathy. Radiographic studies were consistent with pleural, pericardial, and mediastinal hemorrhages. Vitamin K and fresh frozen plasma were given, and he was later discharged on oral phytonadione (vitamin K1). The patient's coagulopathy recurred, necessitating multiple plasma transfusions and prolonged treatment with oral phytonadione. Fifteen weeks after hospital discharge, he presented again with a history of additional brodifacoum ingestion. Neurologic status was initially normal, but in the emergency department he suddenly became comatose soon after emesis was induced with syrup of ipecac. Computed tomography of the brain revealed a subarachnoid hemorrhage that led to brain death less than 24 hours later. This case demonstrates the severe and prolonged coagulopathy that can result from ingestion of brodifacoum, a compound that has a toxic potency about 200-fold that of warfarin and a half-life as much as 60 times longer.

Topics: 4-Hydroxycoumarins; Adult; Blood Coagulation Disorders; Blood Transfusion; Drug Overdose; Emergency Service, Hospital; Humans; Ipecac; Male; Partial Thromboplastin Time; Patient Readmission; Phenobarbital; Plasma; Poisoning; Prothrombin Time; Rodenticides; Subarachnoid Hemorrhage; Suicide; Tomography, X-Ray Computed; Vitamin K

The families of eight unrelated patients were studied with regard to a hereditary deficiency in antithrombin III (ATIII), protein C, or protein S. These deficiencies were recognized in the course of investigations for deep-vein thrombosis (DVT) in the eight patients. A group of 31 individuals (patients and family members), mostly less than 40-year-old was explored. Two cases of AT III deficiency were discovered, as well as 21 of protein C deficiency, and seven of protein S. Ten of the 30 have had recurrent venous thrombosis at the time of bedrest, trauma, surgery, pregnancy, postpartum or during oral contraceptive treatment. Spontaneous DVT occurred in three cases. Seventeen patients had remained asymptomatic till then. Such patients need antithrombotic treatment during surgery or pregnancy. Prophylactic treatment with enoxaparin in one patient (deficiency in protein C) during her second pregnancy is discussed. It seems that low molecular weight heparin may be a safe alternative to unfractionated heparin. Oral anticoagulants are efficient in preventing reoccurring venous thromboembolism in patients with AT III deficiency. The questions of whether oral anticoagulants should be continued in the long-term in patients with protein C or protein S deficiency who have had a DVT, and whether asymptomatic deficient patients should be given any antithrombotic treatment outside circumstances likely to induce a DVT, remain as yet unanswered.

Topics: Adolescent; Adult; Antithrombin III; Antithrombin III Deficiency; Blood Coagulation Disorders; Child; Female; Glycoproteins; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Pedigree; Protein C; Protein C Deficiency; Thrombosis; Vitamin K

Topics: Adult; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Proteins; Female; Fibrinolysis; Glycoproteins; Hemostasis; Humans; Infant, Newborn; Leukemia; Male; Protein C; Protein C Inhibitor; Protein S; Receptors, Cell Surface; Receptors, Thrombin; Thromboembolism; Vitamin K

Our understanding of haemostatic mechanisms has increased in the last decades. This knowledge at the cellular and molecular levels has helped us to appreciate the complexity of haemostatic mechanisms and their disturbance in various disorders. The advance in techniques to measure early activation of coagulation and platelets opens hope of treating acquired bleeding disorders e.g., disseminated intravascular coagulation before the full blown picture. More study needs to be done to define what constitutes normal haemostasis in newborns. The better understanding of control mechanisms of haemostasis will help us in diagnosis and treatment.

Topics: Antithrombin III; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelet Disorders; Blood Platelets; Blood Vessels; Child; Factor VIII; Fibrinolysis; Glycoproteins; Hemophilia A; Hemostasis; Humans; Infant, Newborn; Platelet Storage Pool Deficiency; Prostaglandins; Protein C; Vitamin K; von Willebrand Diseases; von Willebrand Factor

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

Coagulation disorders in liver disease (cirrhosis or acute hepatic necrosis) may be assessed by the laboratory evaluation of factors V, VII, VIII and IX, and fibrinolysis. Tests of platelet and vascular function do not significantly contribute to this assessment. The response of the factors to vitamin K and to fresh frozen plasma contribute to the assessment of bleeding potential and prognosis.

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Cholestasis; Disseminated Intravascular Coagulation; Fibrinolysis; Humans; Liver Cirrhosis; Vitamin K

A short review about the place of coagulation factor VII in the initial phase of blood coagulation is given. A theoretical model describing the relationship between the half-life times of vitamin K-dependent coagulation factors and the control frequency of oral anti-coagulation therapy is presented. The constraints that control frequency imposes on the type of determination to be carried out are discussed.

Topics: Animals; Anticoagulants; Blood Coagulation Disorders; Cattle; Factor IX; Factor IXa; Factor VII; Factor VIIa; Factor X; Factor Xa; Half-Life; Humans; Kinetics; Models, Biological; Vitamin K

Hemostatic changes in liver cirrhosis regularly have complex causes. In addition to a quantitative deficiency of hemostatic factors, also qualitative changes in coagulation factors, disturbances in coagulation factor metabolism and possible iatrogenic disturbances in plasmatic and thrombocytic hemostatic mechanism are to be considered. To diagnose a deficit of hemostatic factors is no problem, but to answer the question which of the numerous pathogenetic factors dominates in an individual case at this moment is very difficult and often impossible.

Topics: Antithrombin III; Aprotinin; Blood Coagulation Disorders; Blood Transfusion; Disseminated Intravascular Coagulation; Erythrocyte Transfusion; Factor XIII; Fibrinogen; Heparin; Humans; Liver Cirrhosis; Platelet Transfusion; Prothrombin; Vitamin K

Topics: Antithrombin III Deficiency; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Fibrinolysis; Hemostasis; Humans; Neoplasms; Thrombosis; Vitamin K

Topics: Aflatoxins; Animals; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Tests; Cats; Cattle; Cattle Diseases; Chemical and Drug Induced Liver Injury; Chickens; Coumarins; Cricetinae; Dogs; Ducks; Goats; Guinea Pigs; Haplorhini; Humans; Mice; Poultry Diseases; Rabbits; Rats; Species Specificity; Vitamin K

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Disseminated Intravascular Coagulation; Fibrinolysis; Hemorrhage; Hemostasis; Humans; Liver Diseases; Thrombosis; Vitamin K

Topics: Animals; Blood Coagulation Disorders; Blood Coagulation Factors; Clofibrate; Ecchymosis; Humans; Male; Middle Aged; Prothrombin Time; Vitamin E; Vitamin K; Warfarin

Topics: Abnormalities, Drug-Induced; Anticonvulsants; Barbiturates; Blood Coagulation Disorders; Chromosome Aberrations; Chromosome Disorders; Female; Fetus; Folic Acid; Humans; Infant, Newborn; Phenytoin; Pregnancy; Pregnancy Complications; Primidone; Succinimides; Trimethadione; Vitamin K; Vitamin K Deficiency Bleeding

Topics: Abruptio Placentae; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelet Disorders; Blood Transfusion; Disseminated Intravascular Coagulation; Embolism, Amniotic Fluid; Factor XIII Deficiency; Female; Fetal Death; Fetal Diseases; Fibrin; Fibrinogen; Fibrinolysis; Hemophilia A; Humans; Liver Diseases; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic; Sepsis; Uterine Hemorrhage; Vitamin K

Topics: Anesthesia; Animals; Anticoagulants; Barbiturates; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Transfusion; Chloral Hydrate; Coumarins; Drug Interactions; Factor VII; Heparin; Heparin Antagonists; Humans; Monitoring, Physiologic; Protamines; Prothrombin Time; Sheep; Surgical Procedures, Operative; Time Factors; Vitamin K

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Flow Velocity; Blood Platelet Disorders; Blood Transfusion; Cholestasis; Chronic Disease; Diagnosis, Differential; Factor V; Fibrinolysis; Hemorrhage; Hemostasis; Humans; Liver; Liver Diseases; Platelet Adhesiveness; Prognosis; Prothrombin Time; Vitamin K

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Transfusion; Hemorrhage; Hemostasis; Heparin; Humans; Liver Diseases; Medical History Taking; Postoperative Complications; Preoperative Care; Surgical Procedures, Operative; Thrombocytopenia; Uremia; Vitamin K

Topics: Abnormalities, Drug-Induced; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Coumarins; Embolism; Female; Fetus; Heart Valve Prosthesis; Hemorrhage; Heparin; Humans; Infant, Newborn; Maternal-Fetal Exchange; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications, Cardiovascular; Thrombophlebitis; Uterus; Vitamin K

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: Afibrinogenemia; Antigens; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Sedimentation; Blood Transfusion; Factor VII Deficiency; Factor XIII Deficiency; Fibrinogen; Hemophilia A; Hemophilia B; Humans; Vitamin K; von Willebrand Diseases

Topics: Antidepressive Agents; Antihypertensive Agents; Appetite Depressants; Blood Coagulation Disorders; Cardiovascular Diseases; Contraceptives, Oral; Coronary Disease; Daunorubicin; Dihydroxyphenylalanine; Heart Diseases; Humans; Iatrogenic Disease; Imipramine; Monoamine Oxidase Inhibitors; Phenothiazines; Shock, Cardiogenic; Transfusion Reaction; Vitamin K

Topics: Administration, Oral; Adrenal Cortex Hormones; Animals; Anti-Bacterial Agents; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Clofibrate; Coumarins; Diuresis; Dogs; Heparin; Humans; Hypnotics and Sedatives; Liver Diseases; Metabolic Diseases; Phenylbutazone; Rats; Salicylates; Sulfonamides; Thrombosis; Uremia; Vitamin K

Topics: Aminocaproates; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Transfusion; Factor V Deficiency; Factor VII Deficiency; Factor VIII; Fibrinogen; Freezing; Hemophilia A; Hemophilia B; Hemorrhage; Hemostasis; Humans; Hypoprothrombinemias; Plasma; Plasma Volume; Prothrombin; Prothrombin Time; Thromboplastin; Vitamin K

Topics: Acetylcholine; Antimetabolites; Aspirin; Autonomic Nervous System; Blood Circulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Calcium; Cell Aggregation; Clot Retraction; Dicumarol; Epinephrine; Factor IX; Factor V; Factor VII; Factor VIII; Factor X; Fibrin; Fibrinogen; Hemorrhage; Hemostasis; Humans; Prothrombin; Prothrombin Time; Surgical Procedures, Operative; Thrombin; Vasoconstrictor Agents; Vasodilator Agents; Vitamin K

Topics: Adult; Blood Coagulation Disorders; Humans; Vitamin K

Vitamin K is frequently administered in cirrhotic patients to correct their coagulopathy, but evidence for such practice is lacking. We aimed to assess whether vitamin K administration increases the levels of the vitamin K-dependent factor VII (FVII), protein C, and protein S in patients with different stages of liver dysfunction. Eighty-nine patients were recruited into four groups: group 1 [hepatitis B virus (HBV) inactive carriers, n = 23]; group 2 [chronic HBV and hepatitis C virus (HCV) hepatitis, n = 21]; group 3 (cirrhosis, n = 24); group 4 (hepatocellular carcinoma, n = 21); and a healthy control group (n = 39). A single dose of 10 mg of vitamin K1 was administered subcutaneously to all patients. Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen, FVII, protein C, total and free protein S, and proteins induced by vitamin K absence (PIVKA)-II (des-gamma-carboxy prothrombin) were measured at baseline and 72 h after vitamin K administration. There was progressive increment in baseline PIVKA-II, and decrements in fibrinogen, FVII, protein C, and protein S across study groups (P < 0.0001). Compared to baseline, vitamin K administration did not affect the measured parameters, whereas TT showed no reduction in any of the groups. Protein C levels declined in group 2, whereas FVII, total and free protein S did not increase in any group, for all parameters. Vitamin K therapy does not cause significant improvements in the majority of coagulation parameters and hence does not seem to be routinely indicated in patients with liver disease.

Topics: Adult; Aged; Biomarkers; Blood Coagulation Disorders; Blood Coagulation Tests; Carcinoma, Hepatocellular; Factor VII; Female; Fibrinogen; Hemorrhagic Disorders; Hepatitis B, Chronic; Hepatitis C; Humans; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Protein C; Protein Precursors; Protein S; Prothrombin; Treatment Outcome; Vitamin K; Young Adult

Patients receiving warfarin who have unstable control of anticoagulation have a significantly lower intake of dietary vitamin K compared with their stable counterparts. We hypothesized that supplementation with oral vitamin K would improve stability in patients with previously unstable control of anticoagulation. Seventy warfarin-treated patients with unstable anticoagulation control were randomly assigned in a double-blinded fashion to receive a daily amount of 150 mug oral vitamin K or placebo orally for 6 months. Measures of stability of anticoagulation control in the 6-month study period were compared with those in the 6 months immediately prior to it. Vitamin K supplementation resulted in a significantly greater decrease in standard deviation of international normalized ratio (INR) compared with placebo (-0.24 +/- 0.14 vs -0.11 +/- 0.18; P < .001) and a significantly greater increase in percentage time within target INR range (28% +/- 20% vs 15% +/- 20%; P < .01). Anticoagulation control improved in 33 of 35 patients receiving vitamin K supplementation; of these, 19 fulfilled our criteria for having stable control of anticoagulation. However, only 24 of 33 patients receiving placebo demonstrated some degree of improvement, with only 7 patients fulfilling the criteria for having stable control. Concomitant supplementation of vitamin K, perhaps through reducing the relative day-to-day variability in dietary vitamin K intake, can significantly improve anticoagulation control in patients with unexplained instability of response to warfarin.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Disorders; Dietary Supplements; Drug Stability; Female; Humans; Male; Middle Aged; Vitamin K; Warfarin

We determine the efficacy of active reversal of warfarin anticoagulation with intravenous vitamin K compared to withholding warfarin in patients requiring urgent orthopedic trauma surgery.. This was a prospective cohort with immediate prehypothesis consecutive retrospective comparative case series conducted at a level 1 university hospital trauma unit.. Forty-eight consecutive patients between 1998 and 2004 in a study composed of a prospective cohort were compared with a retrospective consecutive case series of warfarinized orthopedic trauma patients requiring urgent surgery. The prospective arm directly followed the historic case series from which the hypothesis was generated.. Vitamin K administration.. Primary outcome was time to surgery. Secondary outcomes were problems with active reversal, length of time for warfarin stabilization after surgery, and complications.. The mean time to surgery in warfarinized patients not given vitamin K was 111.9 hours; in the intervention group, it was 67.4 hours, giving a mean difference of 44.5 hours (P = 0.01). Vitamin K reduced the international normalized ratio (INR) to less than 2.0 in 74% of patients within 24 hours. There were no complications of vitamin K administration. A dose of vitamin K costs approximately 1/1000 of a hospital bed day cost. A loading dose of warfarin on the second postoperative day took approximately 1 day longer to reach an INR of greater than 2.0 in the intervention patients than in those who had not been given vitamin K.. Warfarin reversal with vitamin K was successful and facilitated earlier surgery in all patients; the first dose was effective in approximately three quarters of patients. It is cost-effective, with no side effects caused in this study.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Cohort Studies; Drug Administration Schedule; Female; Humans; Injections, Intravenous; Male; Orthopedic Procedures; Preoperative Care; Thrombosis; Treatment Outcome; Vitamin K; Warfarin; Wounds and Injuries

Patients on warfarin for mechanical heart valves are at increased risk for thromboembolic events and intracranial hemmorhage. In current guidelines, a low dose of vitamin K is the recommended treatment for moderate over-anticoagulation based on studies in which only minority patients participating had mechanical heart valves. We performed a randomized controlled trial to compare the efficacy and safety profile of low-dose intravenous vitamin K and fresh frozen plasma (FFP) for patients with mechanical heart valves and mild to moderate over-anticoagulation (international normalized ratio [INR] 4 to 7). In a 24-month period, we randomized 102 patients to (1) vitamin K or (2) FFP. The baseline INR at presentation between the vitamin K group and the FFP group was 4.61 +/- 0.007 vs 4.78 +/- 0.07 (p = 0.11). Six hours after treatment, patients in the FFP group had a significantly lower mean INR compared with the vitamin K group (2.75 +/- 0.06 vs 3.44 +/- 0.10, p = 0.01). No patient in both groups had over-correction (INR < 2). One week later, there was no significant difference in mean INR between both groups (2.7 +/- 0.11 vs 2.56 +/- 0.12, p = 0.41). Fifty-eight percent of patients in the FFP group and 51% in the vitamin K group had an INR within the target range. There were no adverse reactions or outcomes in both groups. In conclusion, intravenous low-dose vitamin K is a safe alternative to FFP infusion for warfarin overdose in patients with mechanical heart valves.

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Component Transfusion; Coagulants; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Infusions, Intravenous; International Normalized Ratio; Male; Middle Aged; Plasma; Prospective Studies; Treatment Outcome; Vitamin K; Warfarin

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Disorders; Female; Heart Valve Prosthesis; Humans; International Normalized Ratio; Male; Middle Aged; Vitamin K; Warfarin

Low dose oral vitamin K rapidly reverses warfarin-associated coagulopathy. Its effect in patients receiving acenocoumarol is uncertain. We compared the effect of withholding acenocoumarol and administering 1 mg oral vitamin K with simply withholding acenocoumarol in asymptomatic patients presenting with INR values between 4.5 and 10.0. The primary end-point of the study was the INR value on the day following randomisation. We found that patients receiving oral vitamin K had more sub-therapeutic INR levels than controls (36.6% and 13.3%, respectively; RR 1.83, 95% confidence interval 1.16, 2.89) and a lower, but non-significant, proportion of INR values in range (50% and 66.6%, respectively) on the day following randomisation. After 5 +/- 1 days, there were more patients with an INR value in range in the vitamin K group than in controls (74.1% and 44.8%, respectively). There were no clinical events during 1 month follow-up. We conclude that the omission of a single dose of acenocoumarol is associated with an effective reduction of the INR in asymptomatic patients presenting with an INR value of 4.5 to 10.0. Furthermore, the use of a 1 mg dose of oral vitamin K results in an excessive risk of over-reversal of the INR.

Topics: Acenocoumarol; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; Chi-Square Distribution; Drug Antagonism; Female; Humans; International Normalized Ratio; Male; Middle Aged; Vitamin K

Excessive anticoagulation due to warfarin use is associated with hemorrhage. Subcutaneously administered vitamin K has not been evaluated for the treatment of warfarin-associated coagulopathy, yet it is widely used.. To show that oral vitamin K is more effective than subcutaneous vitamin K in the treatment of warfarin-associated coagulopathy.. Randomized, controlled trial.. Two teaching hospitals.. Patients with an international normalized ratio (INR) between 4.5 and 10.0.. Warfarin therapy was withheld, and 1 mg of vitamin K was given orally or subcutaneously.. The primary outcome measure was the INR on the day after administration of vitamin K. Secondary outcome measures were hemorrhage and thrombosis during a 1-month follow-up period.. 15 of 26 patients receiving oral vitamin K and 6 of 25 patients receiving subcutaneous vitamin K had therapeutic INRs on the day after study drug administration (P = 0.015; odds ratio, 4.32 [95% CI, 1.13 to 17.44]).. Oral vitamin K lowers INR more rapidly than subcutaneous vitamin K in asymptomatic patients who have supratherapeutic INR values while receiving warfarin.

Topics: Administration, Oral; Aged; Anticoagulants; Blood Coagulation Disorders; Female; Humans; Injections, Subcutaneous; International Normalized Ratio; Male; Middle Aged; Risk Factors; Vitamin K; Warfarin

To evaluate the efficacy of oral menadiol compared to intravenous phytomenadione when correcting coagulopathies associated with cholestasis.. A total of 26 patients with cholestasis and an international normalized ratio (prothrombin time) greater than 1.2, were randomized to receive either 20 mg o.d. for 3 days of oral menadiol (n=12), or 10 mg o.d. of intravenous phytomenadione (n=14) prior to endoscopic retrograde cholangeopancreatography. Liver function tests and international normalized ratio were measured daily for 3 days.. Liver function tests and international normalized ratio were comparable between groups at entry into the study (P > 0.05), but serum albumin was significantly lower in the intravenous phytomenadione group following treatment (P < 0.05). A decrease in international normalized ratio occurred in both groups following administration of vitamin K (P < 0.05). Two patients in the intravenous group required fresh frozen plasma, as failure to normalize international normalized ratio was observed. No adverse drug reactions were observed in either group, and no patient required re-admission for bleeding during a 4-week follow-up period after cholangeopancreatography.. Oral menadiol appears to be an effective alternative to intravenous phytomenadione in the correction of coagulopathies associated with obstructive liver disease. This simplifies the care of patients with deranged clotting times requiring cholangeopancreatography, particularly those to be managed as out-patients.

Topics: Aged; Aged, 80 and over; Blood Coagulation Disorders; Cholestasis; Female; Humans; Male; Middle Aged; Prothrombin Time; Vitamin K; Vitamin K 1

The purpose of our study was to determine whether maternal vitamin K1 administered antenatally improved global coagulation parameters and the levels of specific vitamin K-dependent proteins in low-birth-weight infants.. Thirty-three preterm mothers admitted in labor were assigned in a prospective, blinded fashion to receive either intramuscular vitamin K1 (17) or placebo (16). At delivery cord blood samples were tested for prothrombin time, activated partial thromboplastin time, factor II and protein C activity, and antigen levels. Statistical analysis was by Student t test.. No statistically significant differences could be demonstrated with regard to group mean values for global tests (prothrombin time, activated partial thromboplastin time) or specific vitamin K-dependent protein levels (factor II, protein C) in newborns whose mothers received antenatal vitamin K compared with those who did not.. These results would suggest that antenatal vitamin K1 therapy to mothers < 32 weeks' gestation has no significant effect on the level of vitamin K-dependent factors in the fetus.

Topics: Adolescent; Adult; Antigens; Blood Coagulation; Blood Coagulation Disorders; Cerebral Hemorrhage; Double-Blind Method; Female; Fetal Blood; Humans; Infant, Low Birth Weight; Infant, Newborn; Injections, Intramuscular; Maternal-Fetal Exchange; Obstetric Labor, Premature; Partial Thromboplastin Time; Pregnancy; Prospective Studies; Protein C; Prothrombin; Prothrombin Time; Vitamin K

Antibiotics of the beta-lactam class may cause coagulation defects and bleeding. It has been suggested that N-methyltetrazolethiol (NMTT), a common side chain group at the 3'-position of the cephem or 1-oxacephem frame, could be responsible for the hypoprothrombinemic effect of the antibiotics and that it could inhibit the liver vitamin K-epoxide reductase activity. Flomoxef (6315-S) is a new oxacephem antibiotic which differs from latamoxef because it has [1-(2-hydroxethyl)-1H-tetrazol-5-yl] thiomethyl (HTT) as a side chain at the 3'-position of cephem group instead of NMTT and an extensive modification of 7 beta-acylamino side chain. The present study was carried out to study its effects on vitamin K-dependent blood coagulation parameters in human volunteers. Ten adult patients (6 men and 4 women), suffering from chronic bronchitis, entered into the study. Each patient received ten 1 g i.m. injections of flomoxef at 12-hourly intervals. Apparently, the treatment with this oxacephem antibiotic had no significant effect. PT, PTT and fibrinogen remained in the normal range in all patients and factors II+VII+X, protein C, protein S and AT III were not depleted. The trend was similar both in men and women. Based on the results of the present study, we conclude that flomoxef is an antibiotic that does not exhibit an effect on blood coagulation, even in males.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Bronchitis; Cephalosporins; Chronic Disease; Female; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Protein C; Protein S; Vitamin K

Nine out of 47 (19%) patients on chronic anticoagulation with warfarin, as secondary prophylaxis after myocardial infarction, initially treated with streptokinase, had thromboembolic complications within 4 weeks after sudden (7/25) or gradual (2/22:NS) warfarin withdrawal. The biochemical effects of warfarin withdrawal were repeatedly studied in 20 of the patients during the first 14 days following drug cessation. During the first 4 days, the levels of coagulation factors VII and IX increased more rapidly than proteins C and S. Thus, a gap was created between the factors provoking and inhibiting the coagulation process. Furthermore, plasma concentrations of fibrinopeptide A (FPA) increased, reflecting activation of the coagulation system. These laboratory findings suggest that withdrawal of warfarin creates a transient hypercoagulable state, imposing a risk of thromboembolic events in patients given anticoagulant treatment as secondary prophylaxis following myocardial infarction.

Topics: Adult; Aged; Angina, Unstable; Blood Coagulation Disorders; Blood Coagulation Factors; Cerebrovascular Disorders; Drug Therapy, Combination; Female; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Peripheral Vascular Diseases; Streptokinase; Thromboembolism; Treatment Outcome; Vitamin K; Warfarin

Factors associated with prolongation of the prothrombin time were analyzed in 94 patients with intra-abdominal sepsis. Patients were randomized prospectively to receive either the combination of tobramycin and clindamycin (TM/C) or moxalactam (MOX). This paper presents a retrospective review designed to compare the frequency of prolonged clotting times and to analyze predisposing factors. Prothrombin time (PT) prolongation occurred more frequently in patients given moxalactam (19 of 47 patients) than in patients given the combination of tobramycin and clindamycin (9 of 47 patients) (p less than 0.05). Prolongation of the partial thromboplastin time (PTT) occurred in all patients with a prolonged PT. Liver disease, upper gastrointestinal surgery, and use of cimetidine were more frequent in those patients with abnormal PT/PTT values (p less than 0.05). Two moxalactam-treated patients with subsequent PT/PTT prolongation had individual clotting factors assayed before moxalactam treatment and at the time of detection of the abnormal PT. The activity of clotting factors II, VII, VIII, IX, X, and XII was reduced during MOX therapy. Treatment with vitamin K reversed the abnormality. In view of underlying abnormalities and rapid response to parenteral vitamin K, the mechanism is probably an acute vitamin K deficiency superimposed upon chronic vitamin K deficiency. In patients with intra-abdominal infection, those treated with MOX are more likely to develop abnormal PT than those treated with TM/C. Since abnormal PT/PTT was common even in TM/C patients, supplemental vitamin K should be considered for all seriously ill, older patients with abdominal infections.

Topics: Abdomen; Adult; Aged; Blood Coagulation Disorders; Blood Coagulation Factors; Clindamycin; Drug Combinations; Female; Hemorrhage; Humans; Infections; Male; Middle Aged; Moxalactam; Partial Thromboplastin Time; Prospective Studies; Prothrombin Time; Random Allocation; Risk; Tobramycin; Vitamin K

After withdrawal of warfarin (Marevan), 48-72 hours are required to raise the Thombotest values from a therapeutic level (range 5-10%) to 12% or higher. By i.v. administration of 1 mg vitamin K1 (Konakion) and without changing the dose of the anticoagulant, this effect could be obtained within 24 hours. Furthermore, the effect of vitamin K vanished within 2-5 days. The use of small amounts of vitamin K may therefore be a simple and reliable way of obtaining a rapid, temporary reduction in anticoagulant effect.

Topics: Blood Coagulation; Blood Coagulation Disorders; Drug Antagonism; Humans; Time Factors; Vitamin K; Warfarin

Topics: Age Factors; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Humans; Infant, Newborn; Infant, Premature; Placebos; Prothrombin Time; Vitamin K

High-dose vitamin E intake is known to inhibit vitamin K-derived coagulation factor synthesis, which can cause serious bleeding events such as gastrointestinal bleeding and intracranial hemorrhage. We report a case of coagulopathy induced by marginally increased levels of vitamin E.. A 31-year-old Indian man presented with oral bleeding, black tarry stools, and bruising over his back. He had been taking non-steroidal anti-inflammatory drugs for low backache and vitamin E for hair loss. He had mild anemia with normal platelet count, thrombin time, and prolonged bleeding time, activated partial thromboplastin time, and prothrombin time. Serum fibrinogen was slightly raised. Mixing studies with pooled normal plasma, aged plasma, and adsorbed plasma were suggestive of deficiency of multiple coagulation factors due to acquired vitamin K deficiency. Serum phylloquinone was normal, while prothrombin induced by vitamin K absence-II level was increased. Serum alpha-tocopherol was slightly raised. Upper gastrointestinal endoscopy showed multiple gastroduodenal erosions. A final diagnosis of vitamin E toxicity-related coagulopathy was made. The patient responded well to pantoprazole, vitamin K supplementation, multiple fresh frozen plasma transfusions, and other supportive treatments besides the discontinuation of vitamin E supplementation. The coagulation parameters normalized, and the patient was discharged with complete resolution of symptoms and remained asymptomatic during the follow-up for 6 months.. Vitamin E-related inhibition of vitamin K-dependent factors with coagulopathy may occur even at marginally increased levels of serum vitamin E. This risk becomes significant in patients receiving other drugs that may increase the risk of bleeding.

Topics: Adult; Aged; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Hemorrhage; Humans; Male; Vitamin K

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

Warfarin induces coagulopathy. Guidelines protocolize reversal of supratherapeutic international normalized ratio (INR) in patients dependent on anticoagulation, but practices vary for reversing warfarin-induced coagulopathy after overdose in non-warfarin-dependent patients.. A restrictive approach to coagulopathy reversal in non-warfarin-dependent patients with intentional warfarin overdose may result in worsening coagulopathy, bleeding, and lengthy hospital stay. Given the risk for significant, prolonged coagulopathy, these patients should be treated early with VK1, with subsequent serial INR monitoring and probable additional VK1 dosing. Delayed peak warfarin concentrations support consideration of gastrointestinal decontamination in late presenters.

Topics: Adolescent; Anticoagulants; Blood Coagulation Disorders; Drug Overdose; Female; Hemorrhage; Humans; International Normalized Ratio; Vitamin K; Warfarin

To compare the efficacy of fresh frozen plasma (FFP) with cryopoor plasma (CPP) to treat vitamin K-dependent factor deficiency in a canine in vitro setting.. In vitro laboratory study.. University veterinary medical teaching hospital.. Seven units of FFP and 6 units of CPP from unique canine donors from the university veterinary blood bank.. Canine FFP was adsorbed by oral barium sulfate suspension to mimic vitamin K-dependent coagulopathy. A sequential mixing study was completed by adding FPP or CPP to the adsorbed plasma. Measurements of prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, and factor activities of factors II, VII, and IX (FII, FVII, and FIX) were compared between the 2 treatment groups.. When comparing the sequential addition of CPP or FPP to adsorbed plasma, the following had no statistical significance: PT (P = 0.94), aPTT (P = 0.66), FII (P = 0.05), and FIX (P = 0.90). There was a dose-dependent decrease with PT and aPTT and a dose-dependent increase with FII and FIX. In contrast, after the addition of either CPP or FFP, there was a significant difference between the treatment groups for the concentration of fibrinogen (P = 0.005) and activity of FVII (P = 0.044), with FFP resulting in a greater concentration of fibrinogen and CPP resulting in a greater concentration of FVII. Measurements of factor X (FX) were initially included in the study but were later excluded because FX appeared to be continually adsorbed even after the addition of CPP or FFP.. CPP partially corrected the coagulation times and concentration of vitamin K-dependent coagulation factors to the same degree as FFP. CPP, generally less expensive than FFP, may provide an alternative treatment option for vitamin K-dependent coagulopathies, although in vivo testing is needed.

Topics: Animals; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Dogs; Factor VIII; Fibrinogen; Partial Thromboplastin Time; Plasma; Prothrombin Time; Vitamin K

Acute intoxication with a vitamin K antagonist may cause serious coagulopathy. We report the accidental ingestion of a high dose of acenocoumarol in a young child. Two intravenous administrations of 5 mg of vitamin K, in combination with fast and repeated administration of activated charcoal and sodium sulfate, were sufficient to prevent coagulopathy and related symptoms, despite a confirmed elevated blood acenocoumarol concentration (260 µg/L).

Topics: Acenocoumarol; Anticoagulants; Blood Coagulation Disorders; Child; Eating; Humans; Vitamin K

Topics: Aged; Aged, 80 and over; Anticoagulants; Betacoronavirus; Blood Coagulation; Blood Coagulation Disorders; Coronavirus Infections; COVID-19; Drug Interactions; Drug Monitoring; Female; Host-Pathogen Interactions; Humans; International Normalized Ratio; Male; Middle Aged; Pandemics; Pneumonia, Viral; Predictive Value of Tests; Quarantine; Risk Factors; SARS-CoV-2; Vitamin K

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: Anticoagulants; Blood Coagulation Disorders; Hemorrhage; Humans; Pharmaceutical Preparations; Vitamin K

The impact of vitamin K in ameliorating diabetes-associated complications, especially those linked with platelet activation and coagulation remains unclear. The current study aims to systematically explore and discuss the available evidence on the impact of vitamin K on the diabetes-cardiovascular disease (CVD)-associated complications.. A systematic review of studies published on the MEDLINE (PubMed), EMBASE, and Google Scholar electronic database will be conducted. The review will include studies published from inception until May 25, 2020, reporting on the effect of vitamin K on CVD-related markers, especially coagulation factors and platelet activation in type 2 diabetes mellitus. Before the full-text screening, all studies will be screened by title, abstract, and keywords. The Downs and Black checklist will be used to assess the quality of the studies. Additionally, the Cochrane collaboration tool will also be used to evaluate the risk of bias across the included studies. Kappa Cohen's calculator will be used to assess the level of agreement between the authors.. This systematic review will not require ethical approval, and the results will be distributed through conference and peer-reviewed publications. Our results will assist current and future research scientists on the potential use of vitamin K as a protective therapy against CVD-related complications.. This protocol is registered on the International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42020151667.

Topics: Blood Coagulation Disorders; Diabetes Mellitus, Type 2; Dietary Supplements; Humans; Meta-Analysis as Topic; Systematic Reviews as Topic; Vitamin K

Type 2 heparin-induced thrombocytopenia (HIT 2) is a rare pro-thrombotic disorder occurring in patients treated with heparin. It is defined as a clinical-biological syndrome associating the sudden onset of a thrombocytopenia, characterized by a drop of more than 50% of the initial platelet count, and thrombosis. We report two cases of HIT 2 occurring in patients with major bleeding tendency. The first HIT occurred in a patient whose management, in accordance with current guidelines, made it possible to control the thrombocytopenia and the anticoagulation despite the complexity of adapting and monitoring treatments in the context of recent cerebral hemorrhage. The second refers to an autoimmune HIT, which occurred in a patient whose management required the use of alternative therapies to the standard treatments suggested for HIT 2, to correct the severe refractory thrombocytopenia.

Topics: 4-Hydroxycoumarins; Aged; Anticoagulants; Arginine; Blood Coagulation Disorders; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Hemorrhage; Heparin; Humans; Indenes; Intracranial Thrombosis; Male; Middle Aged; Neurosurgical Procedures; Pipecolic Acids; Sulfonamides; Thrombocytopenia; Vitamin K

Synthetic cannabinoids have become increasingly popular drugs of abuse due to low cost and inability to detect these substances on routine drug screenings. In the United States, incidence of synthetic cannabinoid contamination with long-acting anticoagulant rodenticides (LAARs) resulting in coagulopathy and bleeding complications has been described.We sought to describe the natural history, management approach, and outcomes of bleeding secondary to synthetic cannabinoid-associated LAAR toxicity in an observational case series of patients evaluated at an urban academic medical system.We conducted an observational study of patients with suspected exposure to LAAR-contaminated synthetic cannabinoids and associated bleeding treated within the Johns Hopkins Health System.In this 16 subject cohort, hematuria was the most common bleeding symptom at presentation. The majority of the cohort (75%) had international normalized ratio (INR) > 9.6 at presentation. Of the 13 patients with brodifacoum testing, 12/13 (92%) were positive. Twelve patients (75%) had at least 1 INR value below 2 within 24 hours of the first INR measurement. Of this cohort, 1/16 (6%) died in hospital. The median length of hospital stay was 4 days, (interquartile range = 3-6). The average cost of pharmacological treatment for coagulopathy during inpatient hospitalization was $5300 (range, $2241-$8086).In patients presenting with unexplained coagulopathy it is important for emergency department providers to consider LAAR intoxication and consider formal testing for brodifacoum to assist with treatment planning. Use of a standardized management algorithm including intravenous/oral vitamin K, judicious use of blood products and close laboratory monitoring is essential to optimizing outcomes.

Topics: Adult; Algorithms; Blood Coagulation Disorders; Cannabinoids; Drug Contamination; Female; Humans; Illicit Drugs; Male; Retrospective Studies; Rodenticides; Vitamin K

Synthetic cannabinoids contain many different chemicals and compounds, which pose new health risks to the population using these drugs. In May of 2018 the Center for Disease Control issued a health alert providing information on a multistate outbreak of coagulopathy from exposure to synthetic cannabinoid products containing a Vitamin K-dependent antagonistic agent such as brodifacoum. Recognizing signs, symptoms and imaging findings related to this outbreak is essential for clinicians caring for patients with a history or suspicion of using synthetic cannabinoids. To our knowledge, there are no studies that report the imaging findings demonstrating the coagulopathic complications associated with these synthetic compounds.

Topics: 4-Hydroxycoumarins; Blood Coagulation Disorders; Cannabinoids; Designer Drugs; Emergency Service, Hospital; Fatal Outcome; Hemorrhage; Humans; Male; Middle Aged; Tomography, X-Ray Computed; Vitamin K

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

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

Plasma transfusion is commonly performed for the correction of abnormal coagulation screening tests. The goal of this investigation was to assess the relationship between the dose of plasma administered and changes in coagulation test results in a large and diverse cohort of patients with varying levels of coagulation abnormalities and comorbid disease and in a variety of clinical settings.. In this single-center historical cohort study, all plasma transfusion episodes in adult patients with abnormal coagulation screening tests were extracted between 2011 and 2015. The primary outcome was the proportion of patients attaining normal posttransfusion international normalized ratio (INR ≤ 1.1) with secondary outcomes including the proportion of patients attaining partial normalization of INR (INR ≤ 1.5) or at least 50% normalization in pretransfusion values with respect to an INR of 1.1.. In total, 6779 unique patients received plasma with a median (quartiles) pretransfusion INR of 1.9 (1.6-2.5) and a median transfusion volume of 2 (2-3) units. The majority (85%) of transfusions occurred perioperatively, with 20% of transfusions administered prophylactically before a procedure. The median decrease in INR was 0.4 (0.2-0.8). Complete INR normalization was obtained in 12%. Reductions in INR were modest with pretransfusion INR values <3. Patients receiving ≥3 units of plasma were more likely to achieve at least 50% normalization in INR than those receiving ≤2 units (68% vs 60%; P < .001).. Changes in INR after plasma transfusion were modest at typically used clinical doses, particularly in those with less severely deranged baseline coagulation screening tests. Further studies are necessary to assess the relationships between plasma-mediated changes in INR and clinical outcomes.

Topics: Aged; Aged, 80 and over; Blood Coagulation; Blood Coagulation Disorders; Blood Component Removal; Blood Component Transfusion; Comorbidity; Female; Humans; International Normalized Ratio; Male; Mass Screening; Middle Aged; Plasma Exchange; Platelet Transfusion; Reproducibility of Results; Retrospective Studies; Treatment Outcome; Vitamin K

Warfarin- and superwarfarin-type anticoagulants are commonly used as rodenticides. Exposure to these agents, especially superwarfarins with long-acting anticoagulant effect, can cause life-threatening coagulopathy in humans. Most superwarfarin poisoning cases had an obvious history of exposure, though occult cases without exposure history have also been reported. The current study aims to examine anticoagulant-type rodenticide poisoning in Hong Kong and to identify the similarities and differences between patients with known exposure history and those whose exposure is recognized only through laboratory testing.. The present study was conducted in a tertiary referral clinical toxicology laboratory in Hong Kong. This was a retrospective cohort study of all patients with biochemically confirmed anticoagulant-type rodenticide exposure, from 2010 to 2014.. Superwarfarin was the most common group of anticoagulant-type rodenticides identified (87.8%), in which bromadiolone and brodifacoum were the most frequently encountered. Among the 41 cases identified, 31 had an obvious exposure history, and 10 were occult poisoning in which the context of exposure remained unidentified. All occult poisoning patients without exposure history presented with bleeding events. These occult poisoning cases often went unrecognized by frontline clinicians, leading to delayed investigation and initiation of treatment. This group of patients was associated with a longer time to diagnose coagulopathy (p < 0.001) and confirm rodenticide poisoning (p < 0.05), a higher rate of international normalized ratio (INR) rebound after initiation of antidote (p < 0.001), and a longer time needed for normalizing INR (p < 0.05).. Occult superwarfarin poisoning is an important yet under-recognized differential cause of unexplained coagulopathy. A high index of clinical suspicion and availability of specialized toxicological test for superwarfarins play a vital role in diagnosis and early initiation of appropriate management. The underlying cause of such poisoning remains obscure and warrants further study.

Topics: 4-Hydroxycoumarins; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Disorders; Cohort Studies; Female; Hemorrhage; Hong Kong; Humans; Infant; International Normalized Ratio; Male; Middle Aged; Poisoning; Retrospective Studies; Rodenticides; Vitamin K; Warfarin; Young Adult

Adverse events related to vitamin K antagonists (VKA) represent a major public health problem. Informative tools and educative program contributes to the reduction of iatrogenic risk. The purpose of our study is to assess representations and information needs of patients under VKA therapy in order to develop a suitable therapeutic education program.. Individual semi-structured interviews were conducted among both long term VKA therapy patient and patients initiating VKA. The thematic analysis allowed us to explore patient's speech qualitatively and semi-quantitatively.. The main needs in information concerned the modalities of treatment (27.6%), side effects (24.1%), precautions and management of VKA treatment (24.1%). Origin of the disease (P=0.022) and drug mechanism of action (0.012) were specially asked about by patients initiating their treatment.. Patients under VKA therapy reported needs for information on both their pathology and their anticoagulant therapy. The therapeutic education approach will enable us to adapt the educational tools and messages to the needs of patients under VKA therapy.

Topics: 4-Hydroxycoumarins; Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Disorders; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Indenes; Information Dissemination; Male; Middle Aged; Needs Assessment; Patient Education as Topic; Patient Preference; Vitamin K

A 17-year-old woman, with a history of three operations on the upper gut in early life and intermittent diarrhoea, presented with a history of epistaxis and leg ecchymosis for the previous 3 months. Initial investigation revealed mild anaemia, low serum albumin, moderately elevated aminotransferases and an exceedingly prolonged prothrombin time (PT) which was promptly shortened to normal by intravenous vitamin K. Additional investigations revealed a grossly abnormal glucose hydrogen breath test, a dilated duodenum and deficiencies of vitamins A, D and E. Repeated courses of antimicrobial agents caused prompt but transient shortening of PT and eventually a duodenal-jejunal anastomosis was performed. Since then, up to 36 months later, the patient has been in good general health and PT has been consistently normal with no vitamin K supplementation. Small intestinal bacterial overgrowth has previously been associated with several conditions but this is the first description of its association with vitamin K-responsive coagulopathy.

Topics: Adolescent; Anastomosis, Surgical; Blind Loop Syndrome; Blood Coagulation Disorders; Breath Tests; Dietary Supplements; Ecchymosis; Epistaxis; Female; Glucose; Humans; Hydrogen; Leg; Time Factors; Treatment Outcome; Vitamin K

Acute, unintentional drug-related poisonings lead to an estimated 418,313 ED visits in 2014, according to the latest statistics from the Center for Disease Control and Prevention. While most of these were opiate-related poisonings, anticoagulant rodenticides were the most common cause of rodenticide-related poisoning in the United States. Many clinical syndromes and treatment algorithms have been described for patients with anticoagulant rodenticide poisoning. We report a case of an acute ingestion of two anticoagulant rodenticides and successful reversal of coagulation parameters using 4-factor prothrombin complex concentrate in a fixed-dose approach.

Topics: 4-Hydroxycoumarins; Abdominal Pain; Aged; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Drug Contamination; Drug Dosage Calculations; Hemorrhage; Humans; Illicit Drugs; Male; Rodenticides; Synthetic Drugs; Treatment Outcome; Vitamin K

Synthetic marijuana is a dangerous substance due to its potency, ever-changing composition, and unpredictable side effects. Recently, brodifacoum-contaminated synthetic marijuana has led to multiple deaths and morbidity throughout the USA from severe coagulopathy associated with use of this strain of the drug (brodifacoum is a rodenticide and potent Vitamin K antagonist/anticoagulant). We describe the clinical and radiologic findings in two patients who were diagnosed with, and treated for, ingestion of this new strain of synthetic marijuana. The radiologic manifestations were most notable for hemorrhagic pyelitis/ureteritis. Both patients required hospitalization with Vitamin K supplementation. The radiologic and clinical pictures in these patients are important for radiologists to recognize in order to help guide appropriate patient management.

Topics: 4-Hydroxycoumarins; Adult; Baltimore; Blood Coagulation Disorders; Cannabinoids; Diagnosis, Differential; Disease Outbreaks; Female; Humans; Illicit Drugs; Male; Middle Aged; Poisoning; Rodenticides; Tomography, X-Ray Computed; Vitamin K

In March and April 2018, more than 150 patients presented to hospitals in Illinois with coagulopathy and bleeding diathesis. Area physicians and public health organizations identified an association between coagulopathy and synthetic cannabinoid use. Preliminary tests of patient serum samples and drug samples revealed that brodifacoum, an anticoagulant, was the likely adulterant.. We reviewed physician-reported data from patients admitted to Saint Francis Medical Center in Peoria, Illinois, between March 28 and April 21, 2018, and included in a case series adult patients who met the criteria used to diagnose synthetic cannabinoid-associated coagulopathy. A confirmatory anticoagulant poisoning panel was ordered at the discretion of the treating physician.. A total of 34 patients were identified as having synthetic cannabinoid-associated coagulopathy during 45 hospitalizations. Confirmatory anticoagulant testing was performed in 15 of the 34 patients, and superwarfarin poisoning was confirmed in the 15 patients tested. Anticoagulant tests were positive for brodifacoum in 15 patients (100%), difenacoum in 5 (33%), bromadiolone in 2 (13%), and warfarin in 1 (7%). Common symptoms at presentation included gross hematuria in 19 patients (56%) and abdominal pain in 16 (47%). Computed tomography was performed to evaluate abdominal pain and revealed renal abnormalities in 12 patients. Vitamin K. Our data indicate that superwarfarin adulterants of synthetic cannabinoids can lead to clinically significant coagulopathy. In our series, in most of the cases in which the patient presented with bleeding diathesis, symptoms were controlled with the use of vitamin K

Topics: 4-Hydroxycoumarins; Abdominal Pain; Adult; Anticoagulants; Blood Coagulation Disorders; Blood Transfusion; Cannabinoids; Female; Hematuria; Hemorrhage; Humans; Illinois; International Normalized Ratio; Male; Middle Aged; Patient Readmission; Vitamin K; Warfarin

Vitamin K antagonists (VKA) are currently the most prescribed oral anticoagulant treatment in Tunisia. Despite the standardization of biological monitoring and the better definition of therapeutic objectives, their side effects are a frequent reason for hospitalization.. To evaluate patients' knowledge about their VKA treatment.. We realized a cross-sectional descriptive study in the Cardiology Department of HabibThameur Hospital from September to October 2016. A questionnaire consisting of 14 items was used in a semi-directed interview in order to assess patients' knowledge on their VKA treatment.. Our study included one hundred patients. Mean age was 61 ± 12 years and sex ratio of 1.8. Forty-eight per cent were illiterate. The median duration of AVK intake was 5 years. Atrial fibrillation (AF) was the most frequent indication (57%). Eighty percent of patients had more than five correct answers on the eight items of knowledge: VKA's name (96%), tablet description (93%), dose (99%), time (94%), VKA's effect (70%), INR (56%), treatment's risk (49%) and the target INR (20%). Twenty-two percent had more than four correct answers on the 6 items of know-how: what to do in case of haemorrhage (70%), what to do in case of oblivion (45%), interactions precautions to be observed with food (13%), activities advised against (49%) and medical procedures advised against (27%). In multivariate analysis, only prior VKA information was significantly associated with a better knowledge of VKA (p = 0.027).. Our patients' knowledge on their VKA treatment was insufficient to ensure the safety and efficacy of treatment. The creation of a therapeutic education program on is therefore necessary to reduce the iatrogenic risk of this treatment.

Topics: 4-Hydroxycoumarins; Adult; Aged; Aged, 80 and over; Anticoagulants; Attitude to Health; Blood Coagulation Disorders; Cross-Sectional Studies; Drug-Related Side Effects and Adverse Reactions; Educational Status; Female; Health Knowledge, Attitudes, Practice; Hemorrhage; Hospitalization; Humans; Indenes; Knowledge; Male; Middle Aged; Surveys and Questionnaires; Vitamin K

Since 2013, prothrombin complex concentrate (PCCs) have been approved in the United States for the reversal of anticoagulation induced by vitamin K antagonists. However, there has been limited investigation into their use in trauma and acute-care surgery (ACS).. To investigate the role that 4-factor PCC may have in reversing anticoagulation in the setting of trauma and ACS.. All trauma and ACS patients who presented between March 14, 2014, and August 1, 2015, were included in this retrospective descriptive analysis. Patients receiving 4-factor PCC were compared with patients receiving fresh frozen plasma (FFP) alone. The following data were collected from medical records: age, sex, race, international normalized ratio (INR) at admission (baseline) and after reversal, blood products given, dosing of medication, injury severity score, length of stay, thromboembolic event, death during admission, and death within 90 days after admission.. There were 188 trauma and ACS patients who required reversal of anticoagulation. Of these, 98 patients received FFP and 90 received PCC. Patients who received PCC were at increased risk for death during admission (20% vs 9.2% for FFP group) or within 90 days (39% vs 15%, respectively). Patients in the PCC group had a higher median baseline INR (2.9 vs 2.5 in the FFP group) and a lower postintervention INR (1.4 vs 1.8); consequently, the decrease in INR was greater in the PCC group than in the FFP group (1.5 vs 0.7, respectively). The number of total units of packed red blood cells transfused was significantly higher in patients receiving PCC.. Patients receiving PCC had worse outcomes than those who received FFP. Given that these differences may have resulted from baseline differences between groups, these results mandate further prospective analysis of the use of PCC in trauma and ACS patients.

Topics: Adult; Aged; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Plasma; Retrospective Studies; Treatment Outcome; Vitamin K; Wounds and Injuries

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Disorders; Drug Monitoring; Female; Humans; International Normalized Ratio; Male; Middle Aged; Primary Health Care; Quality Control; Vitamin K

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

Long-acting anticoagulant rodenticides, also called superwarfarins, are known for their greater potency, longer half-life and delayed onset of symptoms. Cases of superwarfarin poisoning can pose a diagnostic and clinical challenge due to a wide array of presentations and prolonged severe coagulopathy requiring months of high-dose oral vitamin K therapy. The most common presentation of long-acting anticoagulant rodenticide poisoning is mucocutaneous bleeding, with other common presentations including haematuria, gingival bleeding, epistaxis and gastrointestinal bleeding. We discuss a case of deliberate self-poisoning with long-acting anticoagulant rodenticides presenting with haematuria and coagulation values above measurable limits. This case is important as it required immediate and maintenance therapy in order to prevent profound bleeding, as well as the evaluation of the patient's psychosocial factors to ensure medical compliance and to prevent refractory complications or repeated self-harm.

Topics: Abdominal Pain; Anticoagulants; Antifibrinolytic Agents; Anxiety Disorders; Blood Coagulation; Blood Coagulation Disorders; Chronic Pain; Comorbidity; Delayed-Action Preparations; Gastrointestinal Hemorrhage; Hematuria; Humans; Male; Middle Aged; Referral and Consultation; Suicide, Attempted; Treatment Outcome; Vitamin K; Warfarin

Topics: 4-Hydroxycoumarins; Blood Coagulation Disorders; Dissociative Disorders; Eating; Female; Follow-Up Studies; Humans; Middle Aged; Risk Assessment; Suicide, Attempted; Vitamin K

The goal of this study was to evaluate the effectiveness of intravenous (IV) vitamin K in cirrhosis.. This was a retrospective study of cirrhotic patients, not on anticoagulation, with administration of IV vitamin K and a baseline INR > 1.5. The primary outcome was the effectiveness of therapy defined by a 30% decrease in INR or a reduction in INR to an absolute value of ≤1.5.. A total of 96 patients were included in the cohort. There was an average decrease in INR of 0.31; however, 60 patients (62.3%) failed to achieve at least a 10% decrease. Sixteen patients (16.7%) met the primary effectiveness endpoint.. The use of IV vitamin K to correct coagulopathy of cirrhosis may not be beneficial.

Topics: Administration, Intravenous; Adult; Antifibrinolytic Agents; Blood Coagulation Disorders; Female; Humans; International Normalized Ratio; Liver Cirrhosis; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Vitamin K

To determine whether the timing of notification of critical international normalized ratio (INR) results (during or after clinic hours) altered the clinician's ability to affect same-day patient care.. Retrospective chart review.. The Anticoagulation Management Service at the University of Alberta Hospital in Edmonton.. A total of 276 patients with critical INR results (> 5.0) separated by at least 30 days were identified to have 200 critical INR results reported during clinic hours and 200 reported after hours.. Differences in the proportion of patients with critical INR results having same-day care altered (by changing warfarin dose, administering vitamin K, or referring for assessment) between those with results reported during clinic hours compared with those with results reported after clinic hours. Differences by highly critical INR results (> 9.0 vs ≤ 9.0) and whether patients experienced thromboembolism or bleeding within 30 days were also assessed.. Same-day patient care was affected for 174 out of 200 (87.0%) critical INR results reported during clinic hours compared with 101 out of 200 (50.5%) reported after clinic hours (. Same-day care was less likely to be affected by critical INR results communicated after hours, most commonly because the patient had already taken their daily warfarin dose. However, after-hours care was still affected for 1 out of 2 patients, which is meaningful and supports current practice.

Topics: After-Hours Care; Aged; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Referral and Consultation; Retrospective Studies; Thromboembolism; Time Factors; Vitamin K; Warfarin

An 85-year-old woman with a diagnosis of choledocholithiasis due to common duct stones gradually developed severe coagulation dysfunction over the course of 27 days after hospitalization. Initial clinical findings were fever, general malaise, and obstructive jaundice. She was treated with fasting, and received cephem antibiotics containing N-methyl-thio-tetrazole. Because the common duct stones were not removed endoscopically, cholecystectomy was scheduled. Coagulation on admission was normal, but gradually became impaired. On the scheduled day of the operation, 27 days after hospitalization, coagulation [both prothrombin time (PT) and activated partial thromboplastin time (APTT)] were severely impaired PT, < 10%; PT-international normalized ratio, 6.29; and APTT, 71.6 s. No other abnormalities were identified. Surgery was postponed and antibiotics were discontinued. Simultaneously, administration of vitamin K was initiated. Six days after starting vitamin K, coagulation dysfunction had resolved and the surgery was safely performed under general anesthesia combined with thoracic epidural anesthesia. Care is warranted regarding coagulation dysfunction due to vitamin K deficiency in patients with hepatobiliary disease treated by fasting and antibiotics.

Topics: Aged; Aged, 80 and over; Blood Coagulation Disorders; Cholecystitis; Female; Gallstones; Humans; Vitamin K

Severe deficiency of vitamin K-dependent proteins in patients not maintained on vitamin K antagonists is most commonly associated with poisoning by or surreptitious ingestion of warfarin, warfarin-like anticoagulants, or potent rodenticides ("superwarfarins"), such as brodifacoum. Serious bleeding manifestations are common. Superwarfarins are 2 orders of magnitude more potent than warfarin and have a half-life measured in weeks. These rodenticides are readily available household environmental hazards and are sometimes consumed accidentally or as manifestations of psychiatric disease. Immediate diagnosis and proper therapy is critically important to minimize morbidity and mortality because this condition, affecting thousands of patients annually, is reversible. Treatment with large doses of oral vitamin K1, often over months to years, to maintain a near-normal prothrombin time can reverse the coagulopathy associated with superwarfarins. Although these patients initially present to various medical specialties, the hematologist is often consulted to offer the definitive diagnosis and proper therapy.

Topics: Aged; Anticoagulants; Blood Coagulation Disorders; Female; Hemorrhage; Humans; Male; Middle Aged; Prognosis; Rodenticides; Vitamin K

Optimal dosing of prothrombin complex concentrate (PCC) has yet to be defined and varies widely due to concerns of efficacy and thrombosis. We hypothesized a dose of 15 IU/kg actual body weight of a three-factor PCC would effectively correct coagulopathy in acute care surgery patients. Retrospective review of 41 acute care surgery patients who received 15 IU/kg (± 10%) actual body weight PCC for correction of coagulopathy. Demographics, laboratory results, PCC dose, blood and plasma transfusions, and thrombotic complications were analyzed. We performed subset analyses of trauma patients and those taking warfarin. Mean age was 69 years (18-94 years). Thirty (73%) trauma patients, 8 (20%) emergency surgery patients, 2 (5%) burns, and 1 (2%) nontrauma neurosurgical patient were included. Mean PCC dose was 1305.4 IU (14.2 IU/kg actual body weight). Mean change in INR was 2.52 to 1.42 (p 0.00004). Successful correction (INR <1.5) was seen in 78 per cent. Treatment failures had a higher initial INR (4.3 vs 2.03, p 0.01). Mean plasma transfusion was 1.46 units. Mean blood transfusion was 1.61 units. Patients taking prehospital warfarin (n = 29, 71%) had higher initial INR (2.78 vs 1.92, p 0.05) and received more units of plasma (1.93 vs 0.33, p 0.01) than those not taking warfarin. No statistical differences were seen between trauma and nontrauma patients. One thrombotic event occurred. Administration of low-dose PCC, 15 IU/kg actual body weight, effectively corrects coagulopathy in acute care surgery patients regardless of warfarin use, diagnosis or plasma transfusion.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Transfusion; Body Weight; Burns; Drug Dosage Calculations; Emergencies; Humans; International Normalized Ratio; Middle Aged; Plasma; Retrospective Studies; Surgical Procedures, Operative; Thrombosis; Vitamin K; Warfarin; Wounds and Injuries; Young Adult

Liver disease results in complex alterations of all 3 phases of hemostasis. It is now recognized that hemostasis is rebalanced in chronic liver disease. The fall in clotting factor levels is accompanied by a parallel fall in anticoagulant proteins. High von Willebrand factor levels counteract defects in primary hemostasis. Conventional coagulation tests do not fully reflect the derangement in hemostasis and do not accurately predict the risk of bleeding. Global coagulation assays (thrombin generation, thromboelastography) reflect the interaction between procoagulant factors, anticoagulant factors, platelets, and the fibrinolytic system and show promise for assessing bleeding risk and guiding therapy. These assays are not yet commercially approved or validated. Prevention of bleeding should not be aimed at correcting conventional coagulation tests. Thrombopoietin receptor agonists were shown to increase the platelet count in cirrhotic patients undergoing invasive procedures but may increase the risk of thrombosis. Rebalanced hemostasis in liver disease is precarious and may be tipped toward hemorrhage or thrombosis depending on coexisting circumstantial risk factors. Bacterial infection may impair hemostasis in cirrhosis by triggering the release of endogenous heparinoids. There are no evidence-based guidelines for hemostatic therapy of acute hemorrhage in liver disease. There is currently inadequate evidence to support the use of recombinant FVIIa, prothrombin complex concentrates, or tranexamic acid in acute variceal or other hemorrhage.

Topics: ADAM Proteins; ADAMTS13 Protein; Antifibrinolytic Agents; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Deamino Arginine Vasopressin; Factor VIIa; Fibrinolysis; Hemorrhage; Hemostasis; Humans; International Normalized Ratio; Liver Diseases; Plasma; Prothrombin Time; Receptors, Thrombopoietin; Recombinant Proteins; Risk Factors; Thrombelastography; Thrombin; Vitamin K

Second generation anticoagulant rodenticides are now the most common rat killers used in China; however, poisoning incidents are frequently reported. The authors retrospectively reviewed 24 patients with vitamin K-dependent coagulation factor deficiency caused by rodenticide poisoning in the past 2 years. The main clinical presentation was hemorrhage, although intracranial bleeding and life-threatening symptoms were not seen. All patients responded to vitamin K, the specific antidote, along with fresh frozen plasma and cryoprecipitate, although prolonged treatment was sometimes required. To avoid such incidents, rodenticide should be safely stored and protective measures used during production and application. Once poisoning has occurred, vitamin K should be administered as soon as possible along with fresh frozen plasma and cryoprecipitate.

Topics: Administration, Cutaneous; Administration, Oral; Adolescent; Adult; Aged; Animals; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Transfusion; Child; Child, Preschool; Factor VIII; Female; Fibrinogen; Hemorrhage; Humans; Male; Middle Aged; Plasma; Rats; Retrospective Studies; Rodenticides; Vitamin K; Young Adult

Topics: Aged; Anesthesia, General; Anticoagulants; Appendicitis; Blood Coagulation Disorders; Blood Coagulation Factors; Cardiomyopathy, Dilated; Consciousness Disorders; Female; Heart Failure; Heart Ventricles; Heart-Assist Devices; Hemostatics; Humans; International Normalized Ratio; Male; Middle Aged; Postoperative Care; Postoperative Complications; Tomography, X-Ray Computed; Vitamin K

There are no studies demonstrating that prothrombin complex concentrates (PCC) improves outcome compared FFP in patients with warfarin-associated intracranial hemorrhage.. A prospective, observational study was conducted of patients who received PCC (Bebulin VH), FFP, or PCC + FFP. All groups received vitamin K 10 mg IV. INR reversal (<1.4), adverse events (venous thromboembolism, myocardial infraction, pulmonary edema), major hemorrhage (new or worsened intracranial hemorrhage, anemia requiring transfusion or GI bleed), and 3-month functional outcome were compared between the groups using Chi squared and logistic regression analysis.. Of 64 patients, PCC alone was used in 16 (mean dose 48 IU/kg), FFP alone in 25 (mean dose 12.5 ml/kg), and PCC + FFP in 23 (median doses 47.4 IU/kg and 11.4 ml/kg, respectively). INR correction occurred in 88, 84, and 70 %, respectively. There were no differences in time to INR correction or adverse events between the groups, but FFP alone was associated with more major hemorrhage after administration (52 %, OR 5.0, 95 % CI 1.6-15.4, P = 0.006) and PCC with less (6 %, OR 0.1, 95 % CI 0.01-0.8, P = 0.033). After adjusting for age, admission GCS, initial INR, and bleed type, the use of PCC was associated with a lower risk of death or severe disability at 3-months (adjusted OR 0.02, 95 % CI 0.001-0.8, P = 0.039), while FFP alone was associated with a higher risk (adjusted OR 51.6, 95 % CI 1.2-2163.1, P = 0.039).. PCC adequately corrected INR without any increase in adverse events compared to FFP and was associated with less major hemorrhage and improved 3-month outcomes in patients with warfarin-associated intracranial hemorrhage.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Component Transfusion; Female; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Logistic Models; Male; Middle Aged; Plasma; Prospective Studies; Treatment Outcome; Vitamin K; Warfarin; Young Adult

Coagulation factor deficiencies are thought to interfere with the detection of the phospholipid-dependent coagulation inhibitor known as lupus anticoagulant (LA). Treatment with vitamin K antagonists (VKA) in particular, is thought to preclude accurate LA assessment. For this reason, the procedure to detect LA includes a mixing test, in which coagulation factor deficiencies are corrected by mixing samples with an equal volume of normal plasma. Despite these mixing tests, interpretation of LA test results is considered difficult in patients receiving high intensity VKA treatment. As a result, VKA treatment is often temporarily discontinued to allow LA assessment. However, whether coagulation factor deficiencies influence LA test results is unclear. We found that neither deficiency of a single coagulation factor, nor a functional coagulation factor deficiency due to high intensity VKA treatment, resulted in false positive dRVVT- or APTT-based (silica clotting time; SCT) LA test results. LA was readily detected in unmixed samples from VKA-treated LA-positive patients with both dRVVT and SCT reagents. VKA treatment caused an underestimation of the strength of the LA with SCT reagents, but did not lead to misclassification of LA status. Although mixing with normal plasma during both screen and confirm tests allowed more accurate assessment of the strength of the LA with SCT reagents in samples with an international normalised >2.5, the mixing procedure itself lead to misclassification of LA in weakly positive samples from patients not treated with VKA. Based on these findings, we conclude that mixing studies are not necessary during LA-assessment.

Topics: Antiphospholipid Syndrome; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Clinical Laboratory Techniques; False Positive Reactions; Female; Humans; International Normalized Ratio; Lupus Coagulation Inhibitor; Pregnancy; Vitamin K

The aim of the study was to determine whether patients treated with anticoagulants in the perioperative period are at higher risk of developing bleeding complications.. Medical records of patients operated for abdominal hernia were analysed. Data concerning demographic characteristic of a group, type of hernia, comorbidities, preoperative anticoagulation therapy and complications were collected. Association of applied anticoagulation therapy with the time of drainage, the amount of drained discharge and the length of hospitalisation was evaluated.. Analysed group consisted of 186 patients. Thirty seven patients were treated with different schemes of anticoagulant therapy before the the surgery. Patients treated with triple anticoagulation therapy (acetylsalicylic acid, low-molecular weight heparin, vitamin K antagonists) had significantly longer time of drainage in comparison to patients treated according to other schemes (p<0.05). The amount of drained discharge and time of hospitalisation did not differ significantly. Neither comorbidities nor the administration of low-molecular weight heparin did not affect the analysed parameters.. Patients operated on abdominal hernia, who were treated with triple anticoagulation therapy in peri-operative period, require significantly longer drainage of the wound what can result in prolonged hospitalisation.

Topics: Adult; Aged; Anticoagulants; Aspirin; Blood Coagulation Disorders; Drainage; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Hernia, Abdominal; Hospitalization; Humans; Male; Middle Aged; Perioperative Period; Poland; Postoperative Complications; Risk Factors; Vitamin K

To compare the safety and effectiveness of three methods of reversing coagulopathic effects of warfarin in patients with potentially life-threatening intracranial hemorrhage.. A retrospective electronic medical record review of 63 patients with warfarin-related intracranial hemorrhage between 2007 and 2010 in an integrated health care delivery system was conducted. The three methods of rapid warfarin reversal were fresh-frozen plasma (FFP), activated factor VII (FVIIa; NovoSevenRT [Novo Nordisk, Bagsværd, Denmark]), and prothrombin complex concentrate (PCC; BebulinVH [Baxter, Westlake Village, California, USA], ProfilnineSD [Grifols, North Carolina, USA]), each used adjunctively with vitamin K (Vit K, phytonadione). We determined times from reversal agent order to laboratory evidence of warfarin reversal (international normalized ratio [INR]) in the first 48 hours and compared INR rebound rates and complications in the first 48 hours.. Reversal with FFP took more than twice as long compared with FVIIa or PCC. To reach an INR of 1.3, mean (±SD) reversal times were 1933 ± 905 minutes for FFP, 784 ± 926 minutes for FVIIa, and 980 ± 1021 minutes for PCC (P < 0.001; P < 0.01 between FFP and FVIIa, P < 0.05 between FFP and PCC). INR rebound occurred in 0 of 31 patients for FFP, 4 of 8 for FVIIa, and 0 of 7 for PCC (P = 0.001). Complications were uncommon. FVIIa was 15 and 3.5 times as expensive as FFP and PCC, respectively.. As an adjunct to Vit K for rapid warfarin reversal, FVIIa and PCC appear more effective than FFP. Either FVIIa or PCC are reasonable options for reversal, but FVIIa is considerably more expensive and may have greater risk of INR rebound.

Topics: Aged; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Electronic Health Records; Emergency Medical Services; Factor VII; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Neurosurgical Procedures; Plasma; Recombinant Proteins; Retrospective Studies; Vitamin K; Warfarin

Topics: 4-Hydroxycoumarins; Ambulatory Care Facilities; Anticoagulants; Blood Coagulation Disorders; Female; Humans; Indenes; Male; Vitamin K

Recent data show that the quality of anticoagulation evaluated in patients receiving vitamin K antagonists (VKA) is not optimal in France. The aim of this retrospective study was to estimate the performances of six French anticoagulant clinics that manage VKA treatments over a 3-year period, from 2009 to 2011.. All clinics used the same rule based software. We determined the time spent in the therapeutic range (TTR), a surrogate end-point of quality of treatment with VKA.. The overall duration of follow-up was 2755 patient-years concerning 2385 patients. The time spent in the therapeutic range 2 to 3 assigned for 89% of the patients, was 73%. On the other hand the time spent in the therapeutic range for the other two INR ranges (2.5-3.5 and 3-4.5) concerning 11% of patients with prosthetic heart valve was lower (63.7% and 68.8% respectively) with an imbalance in favour of the time below the range. In this study, warfarin (Coumadine(®)) and fluindione (Previscan(®)) allowed an equivalent quality of anticoagulation. The 1728 patients of age ranged from 60 to 100 years spent more time in TTR than the 651 younger patients. The percentage of time spent with an INR greater than 5 was extremely reduced which is a guarantee of safety.. These results prove that anticoagulant clinics in France have the same good performances as their counterparts abroad. It can be assumed that a high TTR contributes to a low incidence of both bleedings and thrombosis.

Topics: 4-Hydroxycoumarins; Adolescent; Adult; Aged; Aged, 80 and over; Ambulatory Care Facilities; Anticoagulants; Blood Coagulation Disorders; Child; Female; France; Humans; Indenes; Length of Stay; Male; Middle Aged; Professional Practice; Retrospective Studies; Vitamin K; Young Adult

Prothrombin complex concentrates (PCCs) offer a means for the rapid reversal of warfarin, particularly in the setting of life-threatening bleeding. We evaluated the effectiveness and safety of a PCC-based protocol in patients with warfarin-associated intracerebral hemorrhage (ICH), subdural hematoma (SDH), or subarachnoid hemorrhage (SAH). This was a retrospective case-series review of patients treated with an institution-approved warfarin reversal protocol. Patients with intracranial hemorrhage and known warfarin use with an international normalized ratio (INR)>1.4 received fresh frozen plasma (FFP), vitamin K (phytonadione), and weight-based, 3-factor PCC (Profilnine(®) SD) dose based on the initial INR. Demographic and clinical information, the degree of and time to INR normalization, and adverse events were recorded. The thirty study patients included 19 with primary ICH, 7 with SDH, and 4 with SAH. The mean age was 72.8 (±11) years, including 11 (37%) patients ≥80years old. The median presenting INR was 2.3 (IQR 2-3.3) and post-treatment INR was 1.4 (IQR 1.3-1.5, Z score 6.4, p<0.001). Median time from PCC administration to the first follow up INR was 95 (IQR 50-140) min. No patient's INR increased by more than 0.3 over 72h. Nine patients (30%) underwent neurosurgical procedures after PCC administration and no procedure-related bleeding complication was noted. Adverse events included 3 instances of early hematoma expansion, one ischemic stroke in a patient with endocarditis on post-PCC day 1, one pulmonary embolism 5weeks after PCC treatment, and one coronary in-stent thrombosis 60days after PCC treatment. 6 patients died prior to hospital discharge of anticipated complications of their initial event, and none from identifiable thrombotic complications of PCC. A 3-factor PCC preparation (Profilnine(®) SD), administered with FFP and vitamin K to patients with acute warfarin-associated intracranial bleeding is a reasonable approach to urgent warfarin reversal. However, randomized, prospective trials are needed to verify the safety and clinical effectiveness of PCC administration in this population.

Topics: Aged; Aged, 80 and over; Algorithms; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Female; Hemostatics; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Neurosurgical Procedures; Plasma; Treatment Outcome; Vitamin K; Warfarin

Assessment of a local hemostasis with a compressive, extemporaneous gutter glued to the alveolar crest after tooth avulsion in patients under anticoagulant and/or platelet aggregation inhibitors, and economical impact of this technique.. Ninety-seven tooth extractions were performed in patients under AVK and/or anti-platelet drugs. The interventions were consecutive and concerned 251 teeth (138 different alveolar sites). The extraction alveolus was protected by an absorbable oxycellulose membrane coated with sterilized cyanoacrylate adhesive for medical use. This procedure was used with all patients, whatever the hemorrhagic risk (the only inclusion criterion was INR less than 4 for patients under AVK). All procedures were performed under local anesthesia.. There was one hemorrhagic complication (0.72%) due to mechanical gutter destruction by an antagonist tooth. The adhesive did not run, there was no tissue necrosis, and no wound infection requiring gutter removal.. This local hemostasis procedure is reliable. It may be an alternative to substitution of heparin, without or with hospitalization. This procedure, requiring modification of treatment, greatly decreases healthcare costs. Contra-indications include the presence of an antagonist tooth harmful for the gutter, and patients with impaired consciousness or tongue dyspraxia.

Topics: 4-Hydroxycoumarins; Administration, Topical; Anticoagulants; Blood Coagulation Disorders; Coated Materials, Biocompatible; Cyanoacrylates; Hemostasis, Surgical; Humans; Indenes; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Retrospective Studies; Tissue Adhesives; Tooth Extraction; Vitamin K

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation Disorders; Contusions; Epistaxis; Female; Hematemesis; Humans; Male; Middle Aged; Vitamin K; Vitamins; Warfarin

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

To explore the clinical characteristics and diagnosis and treatment of occult poisoning caused by long-acting anticoagulant rodenticides.. Records of 12 patients from July 2008 to April 2011 diagnosed as anticoagulant rodenticide occult poisoning, who had been misdiagnosed initially at other hospitals were analyzed retrospectively. Elements from the records included clinical symptoms and signs, laboratory findings for prothrombin time (PT) and activated partial prothrombin time (APTT), and initial misdiagnosis and treatment outcome at our hospital.. The clinical presentations of patients were insidious and serious, often presented as skin ecchymose, hematuria, menorrhagia and gastrointestine bleeding. Laboratory examinations showed prolonged PT and APTT; bleeding was controlled effectively by administoring vitamin K1 daily. There were statistical difference between PT and APTT before and after the treatment (P<0.01).. Coagulation disorders might be caused by the reduced acquisition in vitamin K dependent coagulation factors, which tends to be neglected due to a hidden medical history, delayed signs of poisoning, and various organs involved. A detailed patient history and systematic review may improve the diagnostic accuracy. Once diagnosed is made, vitamin K1 should be given as soon as possible.

Topics: Anticoagulants; Blood Coagulation Disorders; Delayed-Action Preparations; Humans; Partial Thromboplastin Time; Prothrombin Time; Rodenticides; Vitamin K

Superwarfarins (brodifacoum, difenacoum, bromodialone and chlorphacinone) are anticoagulant rodenticides that were developed in 1970s to overcome resistance to warfarin in rats. A 26-year-old previously healthy man was admitted to the emergency department with epigastric pain, severe upper and lower gastrointestinal haemorrhage, gingival bleeding and melena. The patient stated that he had been healthy with no prior hospital admissions and no personal or family history of bleeding diathesis. The patient, who later admitted attempted suicide, stated that he had taken 400 g rodenticide including brodifacoum orally for five days prior to admission to hospital. He had oral mucosal bleeding, numerous bruises over the arms, legs and abdomen, and an abdominal tenderness, together with melena. Laboratory tests revealed a haemoglobin level of 12.3 g/dl, leucocyte count of 9.1 × 10(9) /l, haematocrit of 28% and platelet count of 280 × 10(9) /l. The prothrombin time (PT) was > 200 s (normal range 10.5-15.2 s) and the activated partial thromboplastin time (aPTT) was 91 s (normal range 20-45 s). The INR (International normalised ratio) was reported to be > 17 (normal range 0.8-1.2). The thrombin time and plasma fibrinogen levels were in the normal range. The results showed the presence of brodifacoum at a concentration of 61 ng/ml, detected by reversed-phase liquid chromatography.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; 4-Hydroxycoumarins; Adult; Animals; Anti-Ulcer Agents; Anticoagulants; Blood Coagulation Disorders; Emergency Service, Hospital; Gastrointestinal Hemorrhage; Humans; Male; Pantoprazole; Partial Thromboplastin Time; Poisoning; Prothrombin; Rats; Rodenticides; Suicide, Attempted; Treatment Outcome; Vitamin K

Topics: Antithrombins; Aspirin; Blood Coagulation Disorders; Blood Platelet Disorders; Hemorrhagic Disorders; Humans; Receptors, Cytoplasmic and Nuclear; Thrombocytopenia; Vitamin K

Surgery may often be needed for treatment of patients with a periprosthetic joint infection (PJI). This study intended to evaluate the incidence of abnormal coagulation and determine the efficacy of treatment of reversing a coagulation abnormality in patients with PJI. The cohort included 294 patients undergoing treatment of PJI at our institution from 1998 to 2005. In our final analysis, 72 patients (56%) had abnormal coagulation (defined as international normalized ratio >1.12). Fresh frozen plasma and/or vitamin K were administered to 29 of these patients (40%). The international normalized ratio was normalized in only 7 (24.1%) of the latter patients. It appears that more than one half of patients with PJI may have abnormal coagulation even without being exposed to anticoagulation agents, highlighting the possibility that patients with PJI may have circulating levels of biologically active agents that affect coagulation.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Blood Coagulation Disorders; Female; Hip Prosthesis; Humans; Incidence; International Normalized Ratio; Knee Prosthesis; Male; Middle Aged; Plasma; Prosthesis-Related Infections; Retrospective Studies; Treatment Outcome; Vitamin K; Young Adult

The incidence of vitamin K deficiency in infancy has decreased markedly, due to prophylactic administration of vitamin K during the neonatal period. However, vitamin K deficiency bleeding may occur during or after the neonatal period despite prophylactic administration in Japan. Two cases are reported of intracranial hemorrhage associated with coagulopathy in full-term infants who had received prophylactic administration of vitamin K. More reliable methods for prophylactic administration should be established.

Topics: Blood Coagulation Disorders; Cerebral Hemorrhage; Humans; Infant; Infant, Newborn; Male; Treatment Failure; Vitamin K; Vitamin K Deficiency Bleeding

Patients subjected to haemodilution during surgery are at increased risk of bleeding. We hypothesised that, in the acquired dilutional coagulopathy, insufficient haemostasis is due to either insufficient thrombin generation or insufficient fibrin clot formation. In tissue factor-activated plasmas from patients with coagulation deficiency, we measured time curves of thrombin generation and fibrin clot formation (thromboelastography). Investigated were in study A: 10 patients treated with vitamin K antagonist and five healthy subjects; in study B: 30 patients undergoing cardiopulmonary bypass (CPB) surgery and infused with on average 2,000 ml crystalloids and colloids (no major bleeding); in study C: 58 patients undergoing major general surgery, and transfused with >5,000 ml crystalloids, colloids and red cell concentrates, who experienced major bleeding and were post-transfused with fresh frozen plasma. The treatment with vitamin K antagonist led to a progressive reduction in thrombin generation but not fibrin clot formation. In CPB patients, plasma factor levels post-surgery were 53-60% of normal. This was accompanied by moderate reduction in both haemostatic processes. In plasmas from patients undergoing major surgery, factor levels were 38-41% of normal, and these levels increased after plasma transfusion. Taking preset thresholds for normal thrombin generation and fibrin clot formation, at least one of these processes was low in 88-93% of the patients with (persistent) bleeding, but only in 40-53% of the patients without bleeding. In conclusion, the ability of thrombin generation and fibrin clot formation is independently reduced in acquired dilutional coagulopathy, while minimal levels of both are required for adequate haemostasis.

Topics: Aged; Blood Coagulation; Blood Coagulation Disorders; Blood Loss, Surgical; Blood Transfusion; Crystalloid Solutions; Female; Fibrin; Hemodilution; Hemorrhage; Hemostasis; Humans; Isotonic Solutions; Kinetics; Male; Middle Aged; Perioperative Care; Postoperative Hemorrhage; Thrombin; Vitamin K

This study examined the changes of activities of vitamin K-dependent clotting factors (VKDCF) under various pathological conditions and explored the relationship between acquired deficiency of VKDCFs and hemorrhage. Clinical data of 35 patients who were diagnosed as having acquired deficiency of VKDCF were retrospectively analyzed. Coagulation factors involved in the intrinsic and extrinsic pathways were detected in these patients and 41 control subjects. The results showed that the average activities of VKDCFs were decreased in the patients in comparison to the control subjects and significantly increased after treatment of these patients with vitamin K and blood products. Multivariate regression analysis indicated that decreased activity of VKDCF was not an independent risk factor for bleeding disorders owing to deficiency or metabolic disturbance of vitamin K. It was concluded that acquired deficiency of VKDCF occurs under a variety of pathologic conditions and is closely associated with hemorrhagic events. Administration of vitamin K and transfusion of blood products containing high concentrations of VKDCFs helps alleviate the hemorrhagic diseases.

Topics: Adolescent; Adult; Blood Coagulation Disorders; Blood Proteins; Case-Control Studies; Child; Female; Hemorrhage; Humans; Male; Retrospective Studies; Vitamin K; Young Adult

Not all clinicians give vitamin K to severe malaria patients with systemic bleeding. Vitamin K injections may not be useful to stop bleeding in severe malaria patients with predominant hepatocellular jaundice. However, vitamin K may be justified in bleeding patients who have prolonged fasting of more than 3-7 days, underlying malnutrition, or predominant cholestatic jaundice. The decision to give vitamin K to severe malaria patients with systemic bleeding should be based on underlying diseases, type of jaundice, risk for vitamin K deficiency, and allergy to the drug.

Topics: Blood Coagulation Disorders; Drug-Related Side Effects and Adverse Reactions; Hemorrhagic Disorders; Humans; Injections; Malaria; Patient Selection; Vitamin K

Surgical hemostasis may be achieved by using a number of physical, chemical, or biologic methods. One such method is with topical thrombin; however, one member of that class of drugs, bovine-derived thrombin, is associated with potentially serious consequences such as development of immune-mediated coagulopathy. This case report describes a 61-year-old man with peripheral artery disease who presented with a nonhealing ulcer between his toes. Previous exposure to bovine thrombin was unknown but was considered likely because of his extensive surgical history that included procedures in which topical thrombin is commonly used. The patient was admitted and underwent lower extremity revascularization during which he received his first documented exposure to bovine-derived thrombin. By postoperative day 9, he developed a 2.7-cm retroperitoneal hematoma that had progressed to 9.6 cm by postoperative day 13. Evacuation of the hematoma was performed, during which the patient received his second known exposure to topical bovine thrombin. Based on a plasma mixing study on postoperative day 25, presence of factor V and thrombin inhibitors was suspected. A hematology consultation determined that the patient had developed an immune-mediated coagulopathy manifested as exaggerated laboratory coagulation values that continued even after discontinuation of oral anticoagulation, treatment with multiple transfusions of fresh frozen plasma, and intravenous vitamin K administration. The patient was discharged, after no further bleeding episodes had occurred, on postoperative day 29. Although determining previous exposure to bovine-derived thrombin or presence of antibodies can be difficult, a surgeon's index of suspicion should be raised in patients experiencing coagulopathy if they have previously undergone vascular, cardiac, or spinal procedures in which they were most likely exposed to topical thrombin.

Topics: Animals; Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Component Transfusion; Cattle; Hemostasis, Surgical; Hemostatics; Humans; Male; Middle Aged; Peripheral Vascular Diseases; Thrombin; Vitamin K

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Cohort Studies; Drug Administration Schedule; Female; Humans; Injections, Intravenous; Male; Orthopedic Procedures; Preoperative Care; Thrombosis; Treatment Outcome; Vitamin K; Warfarin; Wounds and Injuries

A female patient with significant coagulopathy is presented for case discussion. This case represented a presumed Munchausen exposure to commercially available rat poison that contained one of the superwarfarin chemicals, brodifacoum. Review of the medical literature is undertaken to discuss the diagnostic approach and treatment of superwarfarin exposure. The accidental or intentional exposure to this group of rodenticide represents a significant public health problem that often is not considered by primary care physicians when confronted with coagulopathy.

Topics: 4-Hydroxycoumarins; Animals; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Tests; Female; Humans; Middle Aged; Munchausen Syndrome; Rats; Rodenticides; Vitamin K

Acute subdural hematoma (SDH) is one of the most lethal forms of intracranial injury; several risk factors predictive of a worse outcome have been identified. Emerging research suggests that patients with coagulopathy and intracerebral hemorrhage have a worse outcome than patients without coagulopathy but with intracerebral hemorrhage. The authors sought to determine if such a relationship exists for patients with acute SDH.. The authors conducted a retrospective analysis of consecutive patients admitted to a neurosciences intensive care unit with acute SDH over a 4-year period (January 1997-December 2001). Demographic data, laboratory values, admission source, prior functional status, medical comorbidities, treatments received, and discharge disposition were recorded, as were scores on the Acute Physiology, Age, and Chronic Health Evaluation III (APACHE III). Coagulopathy was defined as an internal normalized ratio>1.2 or a prothrombin time>or=12.7 seconds. Univariate and multivariate analyses were performed on 244 patients to determine factors associated with worse short-term outcomes.. The authors identified 248 patients with acute SDH admitted to the neurointensive care unit during the study period, of which 244 had complete data. Most were male (61%), and the mean age of the study population was 71.3+/-15 years (range 20-95 years). Fifty-three patients (22%) had coagulopathy. The median APACHE III score was 43 (range 11-119). Twenty-nine patients (12%) died in the hospital. Independent predictors of inhospital death included APACHE III score (odds ratio [OR] 4.4, 95% confidence interval [CI] 1.4-13.4, p=0.011) and coagulopathy (OR 2.7, 95% CI 1.1-7.1, p=0.037). Surgical evacuation of acute SDH was associated with reduced inhospital deaths (OR 0.2, 95% CI 0.1-0.6, p=0.003).. Coagulopathy is independently associated with inhospital death in patients with acute SDH. Time to treatment to correct coagulopathy using fresh frozen plasma and/or vitamin K was prolonged.

Topics: Adult; Aged; Aged, 80 and over; APACHE; Blood Coagulation Disorders; Female; Hematoma, Subdural, Acute; Hospital Mortality; Humans; Inpatients; Intensive Care Units; Male; Middle Aged; Plasma; Retrospective Studies; Vitamin K; Vitamins

The aims of this case-control study were to identify in vitamin K antagonist (VKA)-treated unselected patients, factors associated with international normalised ratio (INR) values: (i) greater than 6.0.; and (ii) ranging from 4.0 to 6.0 complicated with bleeding. We also assessed VKA-related morbidity in these patients. During a two-month period, 4,188 consecutive and unselected patients were referred to our Emergency Department. At admission, the medical records of each patient and two age- and sex-matched controls were reviewed for: both duration and indication of VKA therapy, previous medical history of VKA-related haemorrhage, underlying co-morbidities, concomitant medications other than VKA, duration of hospitalization and deaths' causes. Of these 4,188 subjects, 50 case-patients (1.19%) were identified; both case-patients and controls did not differ as regards indications and patterns of VKA therapy. Interestingly, two-thirds of case-patients were women, suggesting that female gender may be a risk factor of VKA over-coagulation onset. We identified the following risk factors of VKA over-coagulation: previous medical history of INR levels over therapeutic range, therapy with antibiotics, amiodarone and proton pump inhibitors, as well as fever. A total of 88% of case-patients were hospitalized; mean duration of patients' hospitalization was seven days [range: 1-56 days]; no patient died from major bleeding. Our study underscores that it is of utmost importance to consider the strength of indication before starting VKA therapy, as this therapy has been responsible for as high as 1.19% of admissions in unselected subjects referred to an Emergency Department. Our data therefore suggest that internists should be aware of VKA-related high morbidity, particularly in situations at risk of VKA over-coagulation.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Amiodarone; Anticoagulants; Blood Coagulation Disorders; Case-Control Studies; Chronic Disease; Comorbidity; Enzyme Inhibitors; Female; Hemorrhage; Humans; Incidence; Length of Stay; Logistic Models; Male; Middle Aged; Prevalence; Proton Pump Inhibitors; Risk Factors; Sex Distribution; Vitamin K

Combined deficiency of vitamin K-dependent clotting factors II, VII, IX and X (and proteins C, S, and Z) is usually an acquired clinical problem, often resulting from liver disease, malabsorption, or warfarin overdose. A rare inherited form of defective gamma-carboxylation resulting in early onset of bleeding was first described by McMillan and Roberts in 1966 and subsequently has been termed 'vitamin K-dependent clotting factor deficiency' (VKCFD). Biochemical and molecular studies identify two variants of this autosomal recessive disorder: VKCFD1, which is associated with point mutations in the gamma-glutamylcarboxylase gene (GGCX), and VKCFD2, which results from point mutations in the vitamin K epoxide reductase gene (VKOR). Bleeding ranges in severity from mild to severe. Therapy includes high oral doses of vitamin K for prophylaxis, usually resulting in partial correction of factor deficiency, and episodic use of plasma infusions or prothrombin complex concentrate. Recent molecular studies have the potential to further our understanding of vitamin K metabolism, gamma-carboxylation, and the functional role this post-translational modification has for other proteins. The results may also provide potential targets for molecular therapeutics and pharmacogenetics.

Topics: Adult; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Proteins; Carbon-Carbon Ligases; Female; Hemorrhage; Humans; Infant; Infant, Newborn; Mixed Function Oxygenases; Plasma; Pregnancy; Vitamin K; Vitamin K Epoxide Reductases

We report the case of a 26-year-old woman suffering from borderline personality disorder (BPD), major depression and bulimia nervosa according to DSM-IV who showed unexplained impairment of the vitamin K-dependent coagulation pathway. Subsequently we discuss different manifestations of self damaging behaviour and comorbidities, as well as psychosocial issues potentially leading to coagulation abnormalities or complications in patients with BPD.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Coagulation Disorders; Borderline Personality Disorder; Diagnosis, Differential; Female; Humans; Olanzapine; Treatment Outcome; Vitamin K

The objective of this study is to show the effectiveness of Factor IX complex concentrate (FIXCC) for rapid reversal of an elevated International Normalized Ratio (INR) in patients with anticoagulation-associated intracerebral hemorrhage (AAICH).. We, retrospectively, analyzed the clinical data of 19 patients with the diagnosis of AAICH from January 2005 to May 2006. A comparison was made among patients treated with FFP and Vit.K [FFP-group (n = 9)] and patients treated with FIXCC in addition to FFP and Vit.K [FIXCC-group (n = 10)]. INR of 1.4 or less was taken as target.. Mean INR on admission for FFP and FIXCC group was 1.84 +/- 0.31 and 2.44 +/- 1.48, respectively (P = 0.315). After administration of therapy, the INR was reduced from 1.84 +/- 0.31 to 1.34 +/- 0.08 (P < 0.05) in FFP group and 2.44 +/- 1.48 to 1.34 +/- 0.07 (P < 0.005) in FIXCC group. Three patients in FFP group (33%) and 8 patients in FIXCC group (80%) reached their target INR in 3-4 h after initiation of therapy (P = 0.012). Mean time taken by both FFP and FIXCC groups to reach the target INR was 8.52 +/- 5.60 h and 4.25 +/- 2.12 h, respectively (P < 0.05). The mean rate of INR correction was 0.06 +/- 0.03 and 0.27 +/- 0.25 per hour for the FFP and FIXCC group, respectively (P < 0.005). There was one death in FIX group and two in FFP group and no thrombotic complications.. Our data suggests that FIXCC in combination with FFP and Vit.K may result in decreased time required when compared to FFP and Vit.K alone for correction of warfarin associated coagulopathy in neurosurgical emergencies.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Disorders; Cerebral Hemorrhage; Drug Interactions; Drug Therapy, Combination; Factor IX; Female; Humans; International Normalized Ratio; Male; Middle Aged; Plasma; Retrospective Studies; Treatment Outcome; Vitamin K; Vitamins; Warfarin

Combined vitamin K-dependent clotting factor (VKCF) deficiency type 2 (VKCFD2) is a rare bleeding disorder caused by mutated vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1) gene.. An Italian patient with moderate to severe bleeding tendency was genotyped, and found to be homozygous for the unique VKORC1 mutation (Arg98Trp) so far detected in VKCFD2. The activity levels of VKCFs were differentially reduced, and inversely related to the previously estimated affinity of procoagulant factor propeptides for the gamma-carboxylase. The normal (factor IX) or reduced antigen levels (other VKCFs) produced a gradient in specific activities. Vitamin K supplementations resulted in reproducible, fast and sustained normalization of PT and APTT. At 24 h the activity/antigen ratios of VKCFs were close to normal, and activity levels were completely (factor VII and IX), virtually (prothrombin, factor X and protein C) or partially (protein S) restored. Thrombin generation assays showed a markedly shortened lag time. The time to peak observed at low tissue factor concentration, potentially mimicking the physiological trigger and able to highlight the effect of reduced protein S levels, was shorter than that in pooled normal plasma. At 72 h the thrombin generation times were normal, and the decrease in activity of procoagulant VKCFs was inversely related to their half-life in plasma. The improved coagulation phenotype permitted the uneventful clinical course after invasive diagnostic procedures.. Modification of coagulation phenotypes in VKCFD2 after vitamin K supplementation was clinically beneficial, and provided valuable patterns of factor specific biosynthesis, half-life and decay.

Topics: Adult; Blood Coagulation Disorders; Blood Coagulation Tests; Female; Half-Life; Homozygote; Humans; Mixed Function Oxygenases; Mutation; Treatment Outcome; Vitamin K; Vitamin K Epoxide Reductases

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

Data on six patients with a Pseudoxanthoma Elasticum (PXE)-like phenotype, characterized by excessive skin folding (resembling cutis laxa) and a deficiency of the vitamin K-dependent clotting factors (II, VII, IX, and X) are presented. A comparison is made between the clinical, ultrastructural, and molecular findings in these patients and those seen in classic PXE and cutis laxa, respectively. Clinical overlap with PXE is obvious from the skin manifestations of yellowish papules or leathery plaques with dot-like depressions at presentation, angioid streaks and/or ocular peau d'orange, and fragmentation and calcification of elastic fibers in the dermis. Important phenotypic differences with PXE include much more severe skin laxity with spreading toward the trunk and limbs with thick, leathery skin folds rather than confinement to flexural areas, and no decrease in visual acuity. Moreover, detailed electron microscopic analyses revealed that alterations of elastic fibers as well as their mineralization were slightly different from those in classic PXE. Molecular analysis revealed neither causal mutations in the ABCC6 gene (ATP-binding cassette subfamily C member 6), which is responsible for PXE, nor in VKORC1 (vitamin K 2,3 epoxide reductase), known to be involved in vitamin K-dependent factor deficiency. However, the GGCX gene (gamma-glutamyl carboxylase), encoding an enzyme important for gamma-carboxylation of gla-proteins, harbored mutations in six out of seven patients analyzed. These findings all support the hypothesis that the disorder indeed represents a separate clinical and genetic entity, the molecular background of which remains to be unraveled.

Topics: Adult; Blood Coagulation Disorders; Blood Coagulation Factors; Cutis Laxa; Dermis; DNA Mutational Analysis; Female; Humans; Male; Middle Aged; Multidrug Resistance-Associated Proteins; Phenotype; Pseudoxanthoma Elasticum; Skin; Skin Diseases; Vitamin K

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Disorders; Dietary Supplements; Drug Stability; Female; Humans; Male; Middle Aged; Vitamin K; Warfarin

Topics: Administration, Oral; Anticoagulants; Blood Coagulation Disorders; Contraindications; Drug Combinations; Factor Xa Inhibitors; Forecasting; Heart Diseases; Hemorrhage; Hemostasis; Humans; Infusions, Parenteral; Point-of-Care Systems; Risk Factors; Thrombin; Vitamin K

The routine pre-operative evaluation of children undergoing elective tonsillectomy and/or adenoidectomy includes coagulation screening tests.. detection of coagulation defects in children with planned tonsillectomy and/or adenoidectomy.. In our study we examined 68 children with abnormal coagulation profile, age 1-17 (average 7.5), 43 male and 25 female. All children underwent coagulation tests (APTT, PT, INR, D-dimer, fibrynogen). In case of twice indicated coagulopathy we diagnosed the levels of the coagulation protein factors.. After second verification 15/68 (22%) patients presented prolonged APTT and/or PT. The most common disorder was isolated prolongation of APTT--47/53 (89%), 3/53 (5.5%) had prolonged PT and 3/53 (5.5%) had both disorders in the same time. After vitamin K admission in 19/53 (36%) coagulation tests returned to normal. 13/53 (24%) patients had the factor XII deficiency, 1 patient had a low activity of von Willebrand factor and temporary deficient of factor VIII. In one case we found temporary deficiency of factors VIII and IX and one boy had isolated, temporary deficiency of factor IX. Rest of patients 21/53 (40%), in which the activity of coagulation factors were normal, underwent surgery despite prolonged APTT without any bleeding during or after surgery.. The coagulation disorders in analized group of children were unstable or inessential, but in a group of 3/68 (4%) nondiagnosed disorders of coagulation tests, may due to heavy bleeding during or after surgery.

Topics: Adenoidectomy; Adolescent; Blood Coagulation Disorders; Blood Coagulation Tests; Child; Child, Preschool; Female; Humans; Infant; International Normalized Ratio; Male; Partial Thromboplastin Time; Postoperative Hemorrhage; Predictive Value of Tests; Preoperative Care; Prothrombin Time; Tonsillectomy; Treatment Outcome; Vitamin K

Patients with a supratherapeutic international normalised ratio (ST-INR) are at risk for bleeding. ST-INR is corrected by withholding warfarin therapy and often by supplementing vitamin K or providing vitamin K-dependent factors; the exact therapeutic decision is based on the extent of the prolonged INR. Currently, ST-INRs are frequently observed in clinical practice due to the use of sensitive recombinant tissue thromboplastin reagents and automation. However, there are scant data correlating an ST-INR with various vitamin K-dependent factors. This prospective cohort study, set in a large tertiary care teaching hospital for the University of Texas Southwestern Medical Center at Dallas, defined the relationship between ST-INR (>5.0) and measured vitamin K-dependent procoagulant factors. Prothrombin time, INR and vitamin K-dependent factors II, VII, IX and X were measured in 78 patients with an INR > 5.0 (ST-INR) who were on warfarin therapy for more than 2 months. There was no significant relationship between the ST-INR and levels of important vitamin K-dependent factors II and X. These data support the recent guidelines that the management of an INR > 5.0 should be driven by the clinical determinants rather than specific INR values per se.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation Disorders; Blood Coagulation Factors; Factor X; Female; Humans; International Normalized Ratio; Logistic Models; Male; Middle Aged; Prospective Studies; Prothrombin; Regression Analysis; Stroke; Venous Thrombosis; Vitamin K; Warfarin

A battery of simple tests for profiling abnormalities of vitamin K-dependent coagulation factors encountered in drug-toxicity studies was verified in rats treated with warfarin (3 and 10 mg/kg, p.o). The thrombotest, or hepaplastin-test, is useful as a follow-up test after routine screening tests for coagulation abnormalities based on PT and APTT, to rule out other coagulation-factor abnormalities. Measurement of coagulation factor activities (factors II, VII, IX and X) using factor-deficient human plasmas provides direct evidence of decreased activities of vitamin K-dependent factors. Furthermore, Echis carinatus venom coagulation time, together with factor II activity, allows us to confirm the generation of PIVKA-II.

Topics: Animals; Biomarkers; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Male; Protein Precursors; Prothrombin; Rats; Rats, Inbred Strains; Toxicity Tests; Vitamin K; Warfarin

The relationship between dietary intake of vitamin K, fat, plasma vitamin K concentrations and anticoagulation response to warfarin within individuals, as well as the contribution of dietary vitamin K to differences in warfarin dose requirements between individuals were investigated in 53 patients on warfarin therapy who had stably controlled anticoagulation. Each patient completed a dietary record of all foods consumed on a daily basis for 4 weeks. Each week a blood sample was taken for measurement of the international normalized ratio (INR), plasma vitamin K, triglycerides and warfarin enantiomer concentrations. The patients' genotype for CYP2C9 was also determined. Regression analysis of the data showed that, for each increase of 100 microg in the daily dietary intake of vitamin K averaged over 4 d, the INR was reduced by 0.2. There was no correlation between warfarin daily dose and average daily dietary vitamin K intake when calculated over 28 d. The regression model for warfarin dose showed that, while dietary vitamin K had no effect, CYP2C9 genotype (P = 2%) and age (P < 1%) significantly contributed to inter-patient variability in warfarin dose requirements. A consistent intake of vitamin K could reduce intrapatient variability in anticoagulation response and thus improve the safety of warfarin therapy.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Body Composition; Dietary Supplements; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Regression Analysis; Treatment Outcome; Vitamin K; Warfarin

Topics: Arnold-Chiari Malformation; Biotin; Blood Coagulation Disorders; Blood Coagulation Factors; Central Nervous System Diseases; Factor IX; Factor VII; Factor X; Female; Humans; Infant, Newborn; Male; Multiple Carboxylase Deficiency; Pregnancy; Prothrombin; Vitamin K

Ten dogs underwent clinical monitoring and laboratory investigations following accidental poisoning with anticoabulant rodenticide products. Hematobiochemical parameters, coagulation profiles and toxicologic analyses of plasma and/or tissues were monitored. In 2 cases necropsy examinations were done. The clinical-pathological aspects of anticoagulant rodenticide poisonings of dogs are then discussed.

Topics: Animals; Anticoagulants; Blood Coagulation Disorders; Case-Control Studies; Dog Diseases; Dogs; Partial Thromboplastin Time; Platelet Count; Poisoning; Rodenticides; Vitamin K

To determine usefulness of the test for proteins induced by vitamin K absence or antagonism (PIVKA) to identify anticoagulant-poisoned dogs, compared with one-stage prothrombin time (OSPT) and activated partial thromboplastin time (APTT) tests.. Retrospective study.. 325 dogs.. Comparisons of results of PIVKA, OSPT, and APTT measurements in dogs with anticoagulant poisoning, hepatic disease, disseminated intravascular coagulation, other blood-related disorders, immune-mediated diseases, or other chronic and acute diseases were performed. Median, quartile, and range values were determined.. PIVKA tests with a 150-second critical value had > 98% specificity and > 90% sensitivity for diagnosis of anticoagulant poisoning versus > 99% specificity and > 79% sensitivity with a 300-second critical value. Comparison of PIVKA values among diagnostic groups revealed significant differences between dogs with anticoagulant poisoning and all other groups.. The PIVKA test with a 150-second critical value is diagnostically useful for distinguishing anticoagulant poisoning from other coagulopathies. Severe liver disease can cause false-positive results. Administration of vitamin K1 or early evaluation (within a few hours of ingesting anticoagulant) may cause false-negative results. Dogs with PIVKA test values > 150 seconds and clinical signs of anticoagulant poisoning can confidently be considered to have anticoagulant poisoning because of the high test sensitivity and specificity.

Topics: Animals; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Diagnosis, Differential; Dog Diseases; Dogs; False Negative Reactions; False Positive Reactions; Partial Thromboplastin Time; Poisoning; Protein Precursors; Prothrombin Time; Retrospective Studies; Sensitivity and Specificity; Vitamin K

An 11-week-old male infant presented with intracerebral hemorrhage associated with coagulopathy manifesting as left hemiparesis, lethargy, and vomiting. Computed tomography demonstrated extensive right frontoparietal intracerebral hemorrhage extending into the ventricular system. Liver function tests revealed abnormal values of transaminases and bilirubin. Blood coagulation studies showed prolonged prothrombin time (PT) and activated partial thromboplastin time (APPT). PT and APTT immediately normalized after the administration of vitamin K and fresh frozen plasma. Right parietal craniotomy and evacuation of the hematoma were performed because of the deterioration in consciousness and left hemiparesis. No vascular abnormality was observed in the hematoma cavity. After surgery, he became alert and the left hemiparesis improved. There is a risk of intracerebral hemorrhage due to vitamin K deficiency even if prophylactic administration of vitamin K was given. Surgical treatment should be considered for the treatment of infantile spontaneous intracerebral hemorrhage, especially if neurological deterioration is present.

Topics: Antifibrinolytic Agents; Blood Coagulation Disorders; Cerebral Hemorrhage; Humans; Infant; Male; Preoperative Care; Vitamin K

Topics: Anticoagulants; Blood Coagulation Disorders; Humans; Solutions; Tablets; Vitamin K; Warfarin

Topics: Anticoagulants; Blood Coagulation Disorders; Humans; Solutions; Tablets; Vitamin K; Warfarin

To date there is no routinely used reliable diagnostic test that can be performed in the post-mortem period to investigate whether a deceased had a coagulation disorder. This paper describes a series of experiments to assess the use of an antigen-based method to investigate the vitamin K-dependent factor II function in the deceased. It illustrates that by using this approach the functional status of factor II can be investigated in the post-mortem period. The abnormal proteins that are investigated by this method appear to remain stable for at least 72 h and potentially up to at least 7 days. The method that is illustrated could thus be reliably used in the post-mortem period to identify a natural or drug-induced factor II abnormality. The potential for other protein components of the coagulation cascade to be investigated by similar antigen-based methodology is suggested.

Topics: Aged; Aged, 80 and over; Anticoagulants; Autopsy; Biomarkers; Blood Coagulation Disorders; Blood Coagulation Tests; Child, Preschool; Female; Humans; Male; Middle Aged; Postmortem Changes; Protein Precursors; Prothrombin; Sensitivity and Specificity; Vitamin K; Warfarin

Topics: Administration, Oral; Aged; Anticoagulants; Blood Coagulation Disorders; Female; Humans; Injections, Subcutaneous; International Normalized Ratio; Male; Middle Aged; Risk Factors; Vitamin K; Warfarin

Topics: Anticoagulants; Blood Coagulation Disorders; Humans; International Normalized Ratio; Risk Factors; Thromboembolism; Vitamin K; Warfarin

Topics: Aged; Anticoagulants; Blood Coagulation Disorders; Cucurbitaceae; Drug Combinations; Drug Interactions; Humans; International Normalized Ratio; Male; Middle Aged; Plant Extracts; Sweden; Vitamin E; Vitamin K; Warfarin

The role of oral Vitamin K administration in the reversal of anticoagulation is not yet clear because of a paucity of data on the early effects of treatment, apparent differences in efficacy between preparations and a lack of data comparing oral with intravenous administration. We have compared the effects on the International Normalized Ratio (INR) and activities of the Vitamin K-dependent clotting factors II, VII, IX and X at 4 h and 24 h after administration of three oral Vitamin K preparations and of intravenous Vitamin K in 64 anticoagulated patients who required non-urgent partial correction of anticoagulation. Our data confirm that correction of anticoagulation is more rapid after intravenous administration of Vitamin K than after oral administration of similar or larger doses. At 24 h, satisfactory correction of INR can be achieved using low-dose Vitamin K given by either the intravenous or oral route. Our data, and that from previous studies, suggest that there may be differences in efficacy between orally administered products. Administration of Vitamin K by either route was accompanied by changes in the activities of the Vitamin K-dependent clotting factors that reflected their respective biological half-lives. In the 24 h after treatment, the relationship between the INR and the individual Vitamin K-dependent clotting factors was similar to that described previously in stable anticoagulated patients. We conclude that the reversal of anticoagulation with warfarin is achieved more rapidly by intravenous administration of Vitamin K. Satisfactory, but slower, reversal of anticoagulation can be effected using oral Vitamin K, but there may be differences in efficacy between the products tested in our study.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation Disorders; Coagulants; Factor IX; Factor VII; Factor X; Humans; Injections, Intravenous; International Normalized Ratio; Prothrombin; Time Factors; Vitamin K; Warfarin

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Carbon-Carbon Ligases; Family Health; Female; Humans; Infant, Newborn; Lebanon; Mutation, Missense; Pedigree; Point Mutation; Vitamin K

Ciprofloxacin, when given to patients previously anticoagulated with warfarin, can occasionally cause an exaggerated hypoprothombinemic response and bleeding diatheses. Two such cases encountered at our institution are presented and data is combined with 64 cases reported to the Food and Drug Administration's (FDA) Spontaneous Reporting System (SRS) database, which included all cases reported from 1987 through 1997. Of 66 total cases the median age was 72 (range 36-94). The mean time to detection of the coagulopathy following the ciprofloxacin challenge was 5.5 days (n = 50). Hospitalization was reported in 15 cases, bleeding in 25 cases, and death in one case. The median prothrombin time (PT) and International Normalized Ratio (INR) was 38.0 (n = 13) and 10.0 (n = 23), respectively. The mean number of medications taken was 6.5 (n = 45). The mean time to correction was significantly shorter between the treated (2.5 days) and the untreated (4.0 days) groups (P < 0. 008). The ciprofloxacin-warfarin coagulopathy occurred most commonly in patients in their seventh decade and in those who require polypharmacy. Active treatment of the coagulopathy results in more rapid resolution than observation alone. Clinicians should be aware of the potential bleeding complications that can occur with the ciprofloxacin-warfarin drug-drug interaction.

Topics: Aged; Aged, 80 and over; Anti-Infective Agents; Anticoagulants; Blood Coagulation Disorders; Ciprofloxacin; Drug Interactions; Female; Humans; Hypoprothrombinemias; Male; Middle Aged; Plasma; Prothrombin Time; Vitamin K; Warfarin

Patients with mutation L394R in gamma-glutamyl carboxylase have a severe bleeding disorder because of decreased biological activities of all vitamin K-dependent coagulation proteins. Vitamin K administration partially corrects this deficiency. To characterize L394R, we purified recombinant mutant L394R and wild-type carboxylase expressed in baculovirus-infected insect cells. By kinetic studies, we analyzed the catalytic activity of mutant L394R and its binding to factor IX's propeptide and vitamin KH(2). Mutant L394R differs from its wild-type counterpart as follows: 1) 110-fold higher K(i) for Boc-mEEV, an active site-specific, competitive inhibitor of FLEEL; 2) 30-fold lower V(max)/K(m) toward the substrate FLEEL in the presence of the propeptide; 3) severely reduced activity toward FLEEL carboxylation in the absence of the propeptide; 4) 7-fold decreased affinity for the propeptide; 5) 9-fold higher K(m) for FIXproGla, a substrate containing the propeptide and the Gla domain of human factor IX; and 6) 5-fold higher K(m) for vitamin KH(2). The primary defect in mutant L394R appears to be in its glutamate-binding site. To a lesser degree, the propeptide and KH(2) binding properties are altered in the L394R mutant. Compared with its wild-type counterpart, the L394R mutant shows an augmented activation of FLEEL carboxylation by the propeptide.

Topics: Amino Acid Substitution; Binding Sites; Blood Coagulation Disorders; Carbon-Carbon Ligases; Enzyme Inhibitors; Humans; Kinetics; Microsomes; Oligopeptides; Point Mutation; Recombinant Proteins; Substrate Specificity; Vitamin K

Cutaneous hypersensitivity reactions to vitamin K are rare. They occur almost exclusively with fat-soluble vitamin K (K1). The lesion is most commonly a pruritic, indurated plaque at the site where the vitamin was injected. Most plaques resolve within 4 to 8 week without sequelae, but some progress to produce scar-like changes that may last for years.

Topics: Adult; Biopsy; Blood Coagulation Disorders; Drug Hypersensitivity; Erythema; Female; Humans; Vitamin K

Superwarfarin sodium exposure or poisoning is a growing public health problem. There were 5133 reported cases of superwarfarin exposure and poisoning in 1988 and 13 423 cases in 1995. Cases may be associated with accidental exposure, suicide attempts, or Munchausen syndrome, and may be difficult to diagnose.. Patients from northern Wisconsin with superwarfarin exposure or poisoning were examined at a tertiary referral center in rural Wisconsin to determine what led to their exposure and to review the clinical manifestations, diagnosis, treatment, and prevention of superwarfarin poisoning.. Eleven cases satisfied the criteria for superwarfarin exposure or poisoning. All 7 children included in the study had accidentally ingested superwarfarin, 2 adults had Munchausen syndrome, and 1 teenager and 1 adult had attempted suicide using superwarfarin. Nine of the 11 cases had taken brodifacoum. The patients who had accidentally ingested superwarfarin or attempted suicide using it were easily diagnosed, while diagnosis was markedly delayed for the 2 patients with Munchausen syndrome. Full reversal of anticoagulation was quickly achieved in the cases of accidental ingestion and attempted suicide. We examined and treated the patients with Munchausen syndrome for months before establishing a diagnosis and fully reversing the anticoagulation. None of the patients in our study died of superwarfarin poisoning.. Superwarfarin exposure or poisoning is a growing public health problem that should be part of the differential diagnosis of patients who present with a coagulopathy consistent with vitamin K deficiency in the absence of coumadin therapy, liver disease, or the use of an inhibitor, and whose conditions do not resolve with large doses of parenteral vitamin K1 therapy.

Topics: 4-Hydroxycoumarins; Adult; Aged; Anticoagulants; Blood Coagulation Disorders; Diagnosis, Differential; Female; Humans; Incidence; Male; Middle Aged; Munchausen Syndrome; Poisoning; Rodenticides; Suicide, Attempted; United States; Vitamin K; Wisconsin

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: Blood Coagulation Disorders; Cholestasis; Humans; Preoperative Care; Prospective Studies; Vitamin K

To determine the influence of vitamin E on phylloquinone activity, one day-old chicks were raised on a masch diet supplemented with different amounts of vitamin E for 31 days. In chicks fed a diet high in vitamin E (4000 mg allrac-alpha-tocopheryl acetate/kg) but adequate in vitamin K (0.14 mg phylloquinone/kg) a threefold increase in prothrombin time and an increase in mortality rate (five out of twelve animals died from increased bleeding tendency) was observed. The inhibiting effect of high dietary vitamin E on procoagulant factors could be prevented by increasing dietary phylloquinone supplementation. Weight development, and feed utilization were insignificantly different in chicks fed different amounts and ratios of vitamins E and K1. Plasma and liver alpha-tocopherol levels correlated with dietary amounts of vitamin E. Increased phylloquinone levels in the diet did not significantly influence alpha-tocopherol concentrations in plasma and liver, but coagulopathy caused by high vitamin E intake could be reversed.

Topics: Animals; Blood Coagulation Disorders; Chickens; Diet; Female; Liver; Prothrombin Time; Vitamin E; Vitamin K; Vitamin K 1; Weight Gain

Topics: Algorithms; Antithrombin III; Biopsy; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Gastrointestinal Hemorrhage; Humans; Hypersplenism; Hypertension, Portal; Liver; Liver Diseases; Liver Transplantation; Thrombocytopenia; Vitamin K

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Proteins; Carbon-Carbon Ligases; Child, Preschool; Drug Resistance; Growth Disorders; Humans; Intellectual Disability; Ligases; Male; Vitamin K

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

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

The sensitivity of the standard prothrombin time (PT) was low when measured on 56 plasmas with a reduced activity of the coagulation factors mainly of the prothrombin complex (factors II, VII and/or X) taken from eight dogs at different times of vitamin K1 therapy after coumarin intoxication. This was demonstrable by use of three different Ca-thromboplastins. With the standard test only plasmas with an excessive decrease of coagulation factor activity (sum of activity decrease of the single factors in relation to the respective reference range [SAD] > 100%) were detectable with sufficient reliability. In contrast, by using a method optimized for dogs (1:20 sample predilution, fibrinogen substitution) and respecting the species specific features of coagulation physiology, pathological PT-values were measured in up to 70% of the samples (dependent on the Ca-thromboplastin) with slight reductions of single factor activity (SAD: 11-25%). Significant differences concerning the sensitivity were seen additionally between the different Ca-thromboplastins. Human placenta thromboplastin in particular, but also rabbit brain thromboplastin, were more sensitive than a preparation of recombinant human tissue factor. The correlation between the PT and the SAD was closer when using the optimized method (r = 0.919-0.954) compared to the standard test (r = 0.771-0.862). In contrast to the standard test, the PT optimized for dogs is, therefore, a reliable screening test to recognize a slight reduction in prothrombin complex. It is especially suitable for monitoring of vitamin K1 therapy after coumarin intoxication.

Topics: Animals; Blood Coagulation Disorders; Coumarins; Dog Diseases; Dogs; Female; Humans; Male; Pregnancy; Prothrombin Time; Reference Values; Sensitivity and Specificity; Vitamin K

Topics: Blood Coagulation Disorders; Female; Humans; Middle Aged; Shock, Hemorrhagic; Vitamin K; Warfarin

Two Devon Rex cats from the same litter, which had no evidence of liver disease, malabsorption of vitamin K or chronic ingestion of coumarin derivatives, were found to have plasma deficiencies of factors II, VII, IX and X. Oral treatment with vitamin K1 resulted in the normalization of these coagulation factors. After taking liver biopsies it was demonstrated that the coagulation abnormality was accompanied by a defective gamma-glutamyl-carboxylase, which had a decreased affinity for both vitamin K hydroquinone and propeptide. This observation prompted us to study in a well-defined in vitro system the possible allosteric interaction between the propeptide binding site and the vitamin K hydroquinone binding site on carboxylase. It was shown that by the binding of a propeptide-containing substrate to gamma-glutamylcarboxylase the apparent KM for vitamin K hydroquinone is decreased about 20-fold. On the basis of these in vitro data the observed defect in the Devon Rex cats can be fully explained.

Topics: Amino Acid Sequence; Animals; Blood Coagulation Disorders; Carbon-Carbon Ligases; Cat Diseases; Cats; Factor X; Kinetics; Ligases; Liver; Molecular Sequence Data; Peptides; Prothrombin; Substrate Specificity; Vitamin K

Topics: Adult; Blood Coagulation Disorders; Carbon-Carbon Ligases; Humans; Ligases; Male; Vitamin K

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: Argininosuccinic Aciduria; Blood Coagulation Disorders; Blood Coagulation Tests; Child; Chronic Disease; Female; Humans; Partial Thromboplastin Time; Prothrombin Time; Vitamin K

Usual coagulation tests--Platelet count, Prothrombin Time (PT), Activated Partial Thromboplastine Time (APTT)--detect most of coagulation abnormalities in preoperative situation. Emergency surgery remains possible without bleeding in most cases. Patient history of haemostatic responses is absolutely necessary to know in addition to coagulation tests. Platelets transfusion may often be avoid in thrombocytopenic patients with platelet count higher than 50,000 mm3. The PT and/or APTT perturbations need further laboratory investigations to estimate the bleeding risk which is not constant. The correction of an antithrombotic treatment is usually easy except for drugs which inhibit platelet aggregation.

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Tests; Emergencies; Humans; Immunoglobulins; Platelet Count; Preoperative Care; Vitamin K

Echis carinatus venom contains proteases capable of activating both normal and descarboxy prothrombin. We showed this venom (Sigma) principally activates prothrombin with almost no factor X activation. Echis time in combination with prothrombin time can predict vitamin K responsiveness since the Echis time is usually normal in the presence of descarboxy prothrombin associated with vitamin K deficiency. 38 patients with abnormal routine prothrombin times (PT) had both coagulant and immunogenic factor II assays along with Echis times done before and after vitamin K. Of 22 patients responding to vitamin K, based on correction of PT, 21 had normal initial Echis times and of 16 not responding, 11 had abnormal Echis times, giving a sensitivity of 95.4% and specificity of 68.8% for vitamin K responsiveness. 90% of patients with a PT/Echis time ratio less than 1.3 and a prolonged Echis time did not correct their PTs with vitamin K therapy. The 5 non-responders with normal Echis times all showed normal initial coagulant and antigenic prothrombin, but 3 had low F V and/or F VII.

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Endopeptidases; Female; Humans; Male; Middle Aged; Prothrombin Time; Viper Venoms; Vitamin K

Hereditary combined deficiency of vitamin K-dependent factors is a rare entity. We report a 7-year-old girl of Arab origin with hereditary deficiency of the procoagulants factors II, VII, IX and X and the natural anticoagulants proteins C and S. The patient is the tenth offspring of a consanguinous marriage and presented at 6 weeks with spontaneous intracerebral haemorrhage. Symptoms improved following plasma infusion. A sibling died at 5 d from uncontrollable umbilical bleeding. Blood coagulation work-up at 6 years showed: factor II:C (activity) 12 U/dl, factor II:Ag (antigen) 40 U/dl; factor VII:C 12 U/dl; factor IX:C 36 U/dl, factor IX:Ag 57 U/dl; factor X:C 17 U/dl, factor X:Ag 54 U/dl; protein C activity 43 U/dl; protein C:Ag 45 U/dl; protein S:Ag 34 U/dl; levels of factors V:C and VIII:C were normal. Assays of coagulation factors in the parents and five of the siblings were within the normal range. Following acute infection and dilantin therapy procoagulant activity levels were reduced further and were partially increased after vitamin K infusion. Crossed immunoelectrophoresis of prothrombin in the presence of calcium lactate revealed a population of des-carboxyprothrombin. Serum vitamin K epoxide levels were undetectable. The data suggest that the defect in our patient stems from abnormal carboxylation of the vitamin K-dependent proteins and that the mode of inheritance is autosomal recessive.

Topics: Blood Coagulation Disorders; Child; Factor VII Deficiency; Factor X Deficiency; Female; Glycoproteins; Hemophilia B; Hemorrhagic Disorders; Humans; Hypoprothrombinemias; Male; Pedigree; Protein C Deficiency; Protein S; Vitamin K; Vitamin K 1

Topics: Adult; Aged; Anaphylaxis; Blood Coagulation Disorders; Female; Humans; Injections, Intravenous; Male; Middle Aged; Vitamin K; Vitamin K 1

The vitamin K metabolism of three patients with factitious purpura due to brodifacoum ingestion was studied. These patients, who presented with bleeding disorders due to deficiency of the vitamin K-dependent blood clotting proteins, were refractory to vitamin K1 at standard doses and required fresh frozen plasma to control bleeding until large doses of vitamin K1 were used. Metabolic studies demonstrated a blockade in vitamin K utilization, consistent with the presence of a vitamin K antagonist, but the patients denied use of anticoagulants. Warfarin assays were negative. We show that the factitious purpura in each patient was due to the surreptitious ingestion of brodifacoum, a potent second generation long-acting vitamin K antagonist used as a rodenticide. The coagulopathies responded to long-term therapy with large doses of vitamin K1. The serum elimination half-time for brodifacoum ranged from 16 to 36 days in these patients. The anticoagulant effect is of long duration, requiring chronic vitamin K treatment. With increasing availability of new rodenticides, factitious purpura due to surreptitious ingestion of these potent vitamin K antagonists is emerging as a new problem, previously associated with warfarin, with important implications for diagnosis and treatment.

Topics: 4-Hydroxycoumarins; Administration, Oral; Adult; Blood Coagulation; Blood Coagulation Disorders; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Purpura; Rodenticides; Vitamin K; Warfarin

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

Topics: Blood Coagulation Disorders; Blood Transfusion; Child; Glycoproteins; Homozygote; Humans; Infant, Newborn; International Cooperation; Liver Transplantation; Plasma; Protein C; Protein C Deficiency; Protein S; Societies, Medical; Vitamin K

A case is presented of exposure to a rodenticide which caused a severe disorder of hemostasis, including macroscopic hematuria, several months after the patient was exposed to it. Response to treatment with vitamin K and barbiturates came only after 70 days. The cause-and-effect relationship between exposure to the rodenticide and the disorder in hemostasis is based on the clinical course and on the late response to treatment.

Topics: Adult; Barbiturates; Blood Coagulation Disorders; Humans; Rodenticides; Vitamin K

Topics: Adult; Blood Coagulation Disorders; Drug Resistance; Humans; Male; Vitamin K

Topics: Acenocoumarol; Blood Coagulation Disorders; Diet, Reducing; Female; Humans; Middle Aged; Vitamin K

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

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

Topics: Adolescent; Blood Coagulation Disorders; Child, Preschool; Female; Humans; Malabsorption Syndromes; Vitamin K; Vitamin K Deficiency

Antithrombin III is a well-known coagulation inhibitor. Its heterozygous deficit is demonstrated through concentrations reduced about by 50 p. 100. On a clinical level, about 40 p. 100 to 70 p. 100 patients present with deep venous thrombosis (visceral on the whole) and pulmonary embolisms from puberty. There are both qualitative and quantitative deficits, these appearing to be mostly frequent. Only calculation of activity in the presence of heparin (co-factor of heparin) enables to diagnose these two types of deficits. Treatment performed includes both AT III concentrated agents and heparin in severe cases. Recurrences prevention is performed thanks to antivitamins K. If surgical treatment or delivery, a prevention of any incidents thanks to a vicarious therapy (AT III concentrated agent) is to be used.

Topics: Adult; Anticoagulants; Antithrombin III Deficiency; Blood Coagulation Disorders; Female; Humans; Male; Pedigree; Pregnancy; Thrombophlebitis; Vitamin K

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

The course of haemostasis defects was investigated in dimethylnitrosamine (DMNA) acute liver necrosis. Before 18 hr there was no evidence of disseminated intravascular coagulation (DIC) nor of abnormal fibrinolysis. At 12 hr the level of the vitamin-K-dependent factors (factors II, VII, IX and X) was reduced to 25-63% of control. Factors V and VIII:C levels decreased to about 10 and 20% by 12 hr. Factor V was the only molecule which decreased significantly by 6 hr. The rapid decrease of these proteins might be related to an early parenchymal functional impairment attested by early structural lesions observed in the endoplasmic reticulum and nucleus. The isolated decrease of factor V in the absence of any significant change in serum transaminase (SGOT and SGPT) levels is proposed, at least in the rat, as an early criterion of hepatic failure.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Chemical and Drug Induced Liver Injury; Dimethylnitrosamine; Liver Diseases; Platelet Count; Rats; Time Factors; Vitamin K

Protein C, discovered by Stenflo in 1976, plays a major role in the regulation of thrombogenic processes. Even moderate deficiencies (0.40 to 0.60 U/ml) can be responsible for serious thromboembolic accidents. The authors evaluated the kits for the immunological assay of protein C, produced by Laboratoire Diagnostica Stago: a immuno-enzymatic method (ELISA) and Laurell's method. Despite the very different characteristics in terms of practicability, threshold of sensitivity and precision, the authors obtained an excellent correlation between these two techniques. The concentrations of protein C Ag obtained in 22 normal plasmas were 0.70 to 1.40 U/ml. In 32 patients with recurrent thrombosis with no apparent cause, 5 had a concentration of protein C Ag less than 0.70 U/ml. The identification of a deficiency of protein C Ag (Vitamin K depend protein) is often made difficulty by the fact that the patients are treated with anti-vitamin K drugs. The ratio between the vitamin K depend pro-coagulation factors and Protein C Ag may provide information about a possible deficiency.

Topics: 4-Hydroxycoumarins; Adult; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Proteins; Enzyme-Linked Immunosorbent Assay; Female; Glycoproteins; Humans; Immunoassay; Immunoelectrophoresis; Indenes; Male; Middle Aged; Protein C; Recurrence; Thromboembolism; Thrombosis; Vitamin K

To elucidate the etiology of hemostatic abnormalities in cases of obstructive jaundice, we occluded the bile duct of rats for one week and found that the moderately jaundiced rats exhibited a marked reduction in the value of Hepaplastin test and Thrombotest with minimum histological changes in liver. All other coagulation and fibrinolysis profiles were within normal limits. These findings exclude the occurrence of a hypercoagulable state or hypofibrinolytic state in the jaundiced rats due to bile duct occlusion. Similar results were obtained in rats with tube choledochostomy. The abnormalities were almost completely prevented by the daily parenteral administration of vitamin K. These observations suggest that malabsorption of vitamin K may be the sole etiologic factor producing hemostatic defects in case of uncomplicated obstructive jaundice.

Topics: Animals; Blood Coagulation Disorders; Blood Coagulation Tests; Cholestasis; Fibrinolysis; Male; Rats; Rats, Inbred Strains; Vitamin K

Topics: Animals; Blood Coagulation Disorders; Blood Coagulation Tests; Disease Outbreaks; Female; Hemorrhage; Male; Swine; Swine Diseases; Vitamin K; Vitamin K Deficiency

Deficiency of vitamin K-dependent coagulation factors caused by the cephalosporin derivatives cefamandole, cefoperazone and moxalactam has been recently recognized. It has been suggested that this adverse reaction may result from vitamin K deficiency caused by eradication of the vitamin K producing intestinal bacteria or inhibition of action of vitamin K 1. Three patients are described in whom hypoprothrombinaemic bleeding developed during administration of cefamandole or cefoperazone. All patients were elderly, had previous malnutrition or had been on parenteral nutrition without vitamin K supplementation. One patient had renal failure. Bleeding manifested 5-14 days after the start of antibiotic treatment. Other causes of the bleeding were excluded. One case was fatal and in 2 cases the coagulopathy was corrected by administration of vitamin K 1 or fresh frozen plasma and cessation of the antibiotic. We recommend prophylactic administration of vitamin K 1 during cefamandole or cefoperazone treatment to patients at risk, i.e. elderly malnourished patients especially those with renal failure or on parenteral nutrition.

Topics: Aged; Blood Coagulation Disorders; Cefamandole; Cefoperazone; Female; Humans; Hypoprothrombinemias; Male; Risk; Vitamin K

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

Topics: Aged; Anti-Bacterial Agents; Blood Coagulation Disorders; Cephalosporins; Humans; Male; Vitamin K

Topics: Aged; Blood Coagulation Disorders; Carbon-Carbon Ligases; Cephalosporins; Female; Humans; Ligases; Male; Middle Aged; Vitamin K

Topics: Adult; Aged; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Protein Electrophoresis; Female; Humans; Male; Prothrombin; Vitamin K; Vitamin K Deficiency

Topics: Blood Coagulation Disorders; Breast Feeding; Female; Hemorrhage; Humans; Infant, Newborn; Pregnancy; Vitamin K

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

Factor VII activity and factor VII cross-reacting material (CRM) in plasma of patients with liver cirrhosis have been studied before and after vitamin K1 parenteral administration. Subjects were divided into two groups according to the absence (group I) or the presence (group II) of the following clinical findings: ascites, portal hypertension, encephalopathy. Factor VII activity and CRM show a statistically significant correlation (p less than 0.001) in all patients. In group II, significantly reduced levels of both activity and CRM were found as compared to the reference and the group I values. No variations were found after vitamin K administration. Different thromboplastins, investigated with respect to their sensitivity for factor VII, acted differently. Patients with normal albumin levels also showed normal levels of factor VII activity and antigen. No correlation was found in group II. The data discussed suggest that in liver cirrhosis with unknown aetiology no immunologically detectable precursor of factor VII is present.

Topics: Adult; Aged; Blood Coagulation Disorders; Cross Reactions; Factor VII; Female; Humans; Isoantigens; Liver Cirrhosis; Male; Middle Aged; Prothrombin Time; Serum Albumin; Vitamin K

Topics: Adult; Blood Coagulation Disorders; Celiac Disease; Female; Humans; Vitamin K

Plasma levels of prothrombin immunoreactive protein (factor II antigen) (II-Ag) and coagulant activity (II-CA) were determined in eight patients with acute hepatitis and in 29 patients with chronic liver disease (cirrhosis). The II-CA was reduced in 23 (62%), II-Ag in 17 (46%), and both were reduced in 13 (36%) of the cases. A disproportionate reduction was noted in 21 (57%); ie, there was more II-Ag found in comparison to the corresponding level of II-Ca. Ninety-six percent (23) of 24 patients with moderate to severe hepatocellular disease showed reduced II-CA levels; 63% (15) showed reduced II-Ag levels, with a disproportionate reduction in II-CA in 67% (16). These data suggest that reduced synthesis as well as impaired carboxylation of prothrombin precursor protein are factors contributing to the coagulopathy in patients with moderate to severe liver disease and that measurement of circulating levels of II-Ag may provide an excellent indication of hepatic synthetic capacity.

Topics: Adolescent; Adult; Blood Coagulation Disorders; Blood Coagulation Tests; Child; Female; Hepatitis; Humans; Infant; Liver; Liver Cirrhosis; Liver Diseases; Male; Middle Aged; Prothrombin; Vitamin K

A 17-year-old girl swallowed at least 50 Duroferon duretter. Each tablet contains ferrous sulphate equivalent to 0.1 g Fe2+. Thus, a total of 5 g Fe2+ was ingested. Vitamin K-dependent coagulation factors dropped within the next hours to very low levels. Thrombotest showed less than 3% of normal coagulation activity 8 h after oral intake. Recovery was uneventful except for laboratory evidence of transient liver damage. The rapidity by which the early coagulation deficiencies developed and the lack of evidence of disseminated intravascular coagulation suggested a direct effect of iron on coagulation factors. In vitro studies confirmed that iron in concentrations that may have been attained in vivo, altered the functional activity of several coagulation factors. Monitoring the vitamin K-dependent coagulation factors may be a simple and useful parameter in acute iron intoxication.

Topics: Acetaminophen; Adolescent; Alcohol Drinking; Blood Coagulation Disorders; Female; Humans; Iron; Iron-Dextran Complex; Leukocyte Count; Platelet Count; Prothrombin Time; Salicylates; Suicide, Attempted; Vitamin K

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Chemical Phenomena; Chemistry; Factor IX; Factor VII; Factor X; Humans; Prothrombin; Vitamin K

Factor IX antigen and activity were assayed in a group of patients with liver disease and in a group of patients in coumarin therapy. In patients with liver disease there was a similar decrease in activity and antigen. On the other hand factor IX activity is decreased in coumarin treatment with factor IX antigen remaining normal. Factor IX electrophoretic mobility in liver disease is normal.

Topics: Blood Coagulation Disorders; Coumarins; Factor IX; Hemophilia B; Humans; Immunoassay; Liver Diseases; Vitamin K

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 new factor VII abnormality is presented. The propositus was a 9-yr-old child who presented a mild bleeding tendency characterized by epistaxis and easy bruising. The parents were not consanguineous, but they came from the same area. The laboratory features were mild prolongation of prothrombin time and P.P. test and normal partial thromboplastin and Stypven cephalin clotting times. The Thrombotest was moderately prolonged. Factor VII was 40%-50% of normal using rabbit or human brain thromboplastin, but only 13%-24% using ox brain thromboplastin. Factor VII cross-reacting material (CRM) was about 50% of normal. The father, a paternal aunt, and a paternal cousin showed similar clinical and laboratory findings. The brother of the propositus, the mother, and other members of her family showed about 50% factor VII activity and CRM and were considered to be heterozygotes for true factor VII deficiency. Similar findings were also present in the father and in the brother of the affected cousin. The defect in the propositus seems to consist of a double heterozygosity between abnormal factor VII and heterozygous factor VII true deficiency. The factor VII abnormality appears to consist of abnormal reactivity toward ox brain tissue thromboplastins and appears to be different from previously described factor VII abnormalities. The name factor VII Paudua2 is proposed for this condition.

Topics: Adolescent; Adult; Antigens; Blood Coagulation Disorders; Child; Cross Reactions; Factor VII; Female; Humans; Male; Pedigree; Vitamin K

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Humans; Tissue Extracts; Vitamin K

Topics: Administration, Oral; Animals; Anticoagulants; Biomarkers; Blood Coagulation Disorders; Blood Proteins; Cattle; Cold Temperature; Factor VII; Factor VII Deficiency; Factor X; Factor X Deficiency; Humans; Hypoprothrombinemias; Kaolin; Protein Precursors; Prothrombin; Prothrombin Time; Rabbits; Thromboplastin; Vitamin K

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Humans; Vitamin K

In a prospective study the daily milk intake and weight gain were recorded in 169 healthy newborn infants during the first week of life. Factor II, V and VII activities were determined on the fourth day using a capillary blood method with hematocrit correction factor. Late onset of feeding showed a major influence on factor II and VII activities. In full-term newborns factor II was correlated to the birth weight. Mode of delivery, color of amniotic fluid, umbilical cord round the neck, Apgar score and postnatal vitamin K prophylaxis showed no significant influence. In infants with abnormal cardiotocographic findings higher levels of factor II were determined. This can be explained by stress-induced liver maturation.

Topics: Amniotic Fluid; Apgar Score; Blood Coagulation Disorders; Blood Coagulation Factors; Delivery, Obstetric; Female; Humans; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Newborn, Diseases; Pregnancy; Vitamin K

Topics: Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Transfusion; Hemostatics; Humans; Vitamin K

The decreased capacity of the liver to synthesize proteins is the main cause of decreased blood levels of clotting factors II, V, VII, IX, X and of antithrombin III in patients with liver disease. Therefore, determination of the activity or concentration of these coagulation proteins is a useful test of liver function and guide to prognosis, provided that other mechanisms which may influence the blood level are carefully considered. Clotting factor assays have an only limited value for the differential diagnosis in liver disease.

Topics: Acute Disease; Antithrombins; Blood Coagulation Disorders; Blood Coagulation Tests; Carcinoma, Hepatocellular; Chronic Disease; Factor IX; Factor V; Factor VII; Factor VIII; Factor X; Factor XIII; Fibrinogen; Hepatitis; Humans; Jaundice, Chronic Idiopathic; Liver Cirrhosis; Liver Diseases; Liver Function Tests; Liver Neoplasms; Neoplasm Metastasis; Prothrombin; Vitamin K

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

Topics: Blood Coagulation Disorders; Diarrhea, Infantile; Female; Humans; Infant; Malabsorption Syndromes; Purpura; Vitamin K; Vitamin K Deficiency

Henoch-Schönlein purpura is classically described as a systemic vasculitis without known platelet or clotting abnormality. A 15-year-old boy with Henoch-Schönlein purpura experienced a major hemorrhagic diathesis that was responsive to parenterally administered vitamin K. We believe that the gastrointestinal vasculitis prevented the absorption of available vitamin K necessary for the synthesis of clotting factors. Early treatment with parenteral vitamin K in similar cases should be considered.

Topics: Adolescent; Blood Coagulation Disorders; Humans; IgA Vasculitis; Male; Vitamin K

The reduction of prothrombin level below 5% in a patient with intrahepatic cholestasis of pregnancy is reported. The necessity of controlling the Quick level or better factors II, VII, IX and X is discussed. A well-timed Vitamin K therapy in all cases with impaired secretion of bile during pregnancy is recommended.

Topics: Blood Coagulation Disorders; Cholestasis; Female; Humans; Pregnancy; Pregnancy Complications, Hematologic; Vitamin K

Simple coagulation tests, easily performed in every laboratory allowing diagnosis and differential diagnosis of acute acquired defects of coagulation are reported. The therapeutic possibilities and their practice are presented.

Topics: Acute Disease; Adult; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Calcium; Factor VIII; Female; Fibrinogen; Heparin; Humans; Male; Vitamin K

A young woman presented with a 2 year history of a severe bleeding disorder and marked deficiencies in all four vitamin-K-dependent factors. Metabolic studies with tracer doses of tritium-labelled vitamin K1 suggested that the patient might be taking an oral anticoagulant; and subsequently her plasma was found to contain a substance identical to phenindione in its spectrophotometric and chromatographic properties. The half-disappearance times of factors II, IX, X were measured after the administration of a concentrate of these factors and were found to conform with published figures. The concentrate controlled the patient's excessive bruising and prolonged skin and gingival bleeding. It would therefore seem that factor VII may not be essential in reversal of the bleeding disorder induced by anticoagulant overdose.

Topics: Adult; Anemia; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Chromatography, Gas; Chromatography, Thin Layer; Diabetes Complications; Female; Glucosephosphate Dehydrogenase; Hematemesis; Hematuria; Humans; Menorrhagia; Phenindione; Self Medication; Spectrum Analysis; Substance-Related Disorders; Vitamin K; 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: Blood Coagulation Disorders; Humans; Liver Cirrhosis; Male; Middle Aged; Prothrombin; Vitamin K

Topics: Blood Coagulation Disorders; Dermatologic Surgical Procedures; Factor IX; Factor VIII; Hemorrhage; Hemorrhagic Disorders; Humans; Medical History Taking; Vitamin K

Topics: Aminocaproates; Blood Coagulation Disorders; Blood Coagulation Factors; Cholestasis; Disseminated Intravascular Coagulation; Fibrin Fibrinogen Degradation Products; Heparin; Hepatitis; Humans; Liver Circulation; Vitamin K

Topics: Animals; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Cattle; Cattle Diseases; Denmark; Dicumarol; Dogs; Factor IX; Factor V; Factor VII; History, 20th Century; Humans; Plant Poisoning; Prothrombin; Rats; United States; Vitamin K

Topics: Adrenal Glands; Animals; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Body Weight; Cold Temperature; Factor V; Factor VII; Factor X; Feces; Fibrinogen; Hair; Hemoglobins; Iodine; Male; Organ Size; Prothrombin Time; Rats; Testis; Thyroid Gland; Vitamin K

Topics: Animals; Antifibrinolytic Agents; Blood Coagulation Disorders; Coagulants; Flavonoids; Hemorrhage; Hemorrhagic Disorders; Hemostatics; Humans; Purpura; Snake Venoms; Venoms; Vitamin K

Topics: Adult; Blood Coagulation Disorders; Blood Coagulation Tests; Hemorrhage; Humans; Male; Malingering; Neurotic Disorders; Prothrombin Time; Self Medication; Vitamin K; Warfarin

Topics: Adrenal Cortex Hormones; Anabolic Agents; Blood Coagulation Disorders; Estrogens; Hemorrhage; Humans; Syndrome; Vitamin K

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: Alanine Transaminase; Animals; Animals, Newborn; Blood Coagulation; Blood Coagulation Disorders; Cats; Depression, Chemical; Dose-Response Relationship, Drug; Drug Interactions; Factor V Deficiency; Factor VII; Factor VII Deficiency; Female; Folic Acid; Hemophilia A; Hypoprothrombinemias; Liver; Maternal-Fetal Exchange; Phenobarbital; Phenytoin; Pregnancy; Primidone; Rats; Vitamin K

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: Adenosine Diphosphate; Blood Coagulation Disorders; Epinephrine; Female; Gastrointestinal Hemorrhage; Humans; Infant, Newborn; Maternal-Fetal Exchange; Platelet Adhesiveness; Pregnancy; Salicylates; Vitamin K

Topics: Adult; Aged; Blood Coagulation Disorders; Coumarins; Diagnosis, Differential; Female; Gastrointestinal Hemorrhage; Hematoma; Hemophilia A; Humans; Intestinal Diseases; Intestine, Small; Jejunum; Male; Middle Aged; Radiography; Vitamin K

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: Blood Coagulation Disorders; Blood Transfusion; Drainage; Female; Hemoglobinometry; Hemorrhage; Hemothorax; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Mediastinum; Pleura; Radiography; Rupture; Thymus Gland; Vitamin K

Topics: Alanine Transaminase; Anemia; Aspartate Aminotransferases; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Blood Transfusion; Cerebral Hemorrhage; Ecchymosis; Female; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Male; Prognosis; Prothrombin; Prothrombin Time; Seizures; Spinal Puncture; Subarachnoid Hemorrhage; Thrombin; Thromboplastin; Vitamin K

Topics: Blood Coagulation Disorders; Female; Humans; Hypercholesterolemia; Prothrombin Time; Vitamin K

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Proteins; Child, Preschool; Dehydration; Dietary Proteins; Emaciation; Factor V Deficiency; Humans; Infant; Kwashiorkor; Liver Function Tests; Nutrition Disorders; Protein-Energy Malnutrition; Prothrombin Time; Vitamin K

Topics: Alveolectomy; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Hemophilia A; Hemostasis; Humans; Oral Hemorrhage; Prothrombin; Tooth Extraction; Vitamin K

Topics: Blood Coagulation Disorders; Blood Specimen Collection; Blood Transfusion; Cerebral Hemorrhage; Female; Fetal Diseases; Foreign Bodies; Hematocrit; Hemorrhage; Humans; Infant, Newborn; Labor, Obstetric; Male; Medical History Taking; Pregnancy; Scalp; Vitamin K

Topics: Blood Coagulation Disorders; Czechoslovakia; Drug Utilization; Hemorrhage; Humans; Vitamin K; Vitamin K 1

Topics: Administration, Oral; Blood Coagulation Disorders; Blood Platelets; Exchange Transfusion, Whole Blood; Fibrinogen; Humans; Infant, Newborn; Injections, Intravenous; Prothrombin Time; Thrombelastography; Vitamin K

Topics: Adult; Aged; Anticoagulants; Blood Coagulation Disorders; Female; Heparin; Humans; Intestinal Absorption; Male; Middle Aged; Vitamin K; Vitamin K Deficiency

Topics: Acute Disease; Blood Coagulation Disorders; Heparin; Humans; Liver Cirrhosis; Vitamin K

Topics: Animals; Bile; Biotin; Blood Coagulation Disorders; Female; Prothrombin Time; Rats; Vitamin B Deficiency; Vitamin K

Topics: Blood Coagulation; Blood Coagulation Disorders; Embolism; Factor X; Heparin; Humans; Injections, Subcutaneous; Postoperative Complications; Thromboembolism; Thrombosis; Urogenital System; Vitamin K

Topics: Ammonium Sulfate; Animals; Barium; Barium Sulfate; Biological Assay; Blood Coagulation Disorders; Blood Coagulation Tests; Cattle; Chromatography; Chromatography, Gel; Chromatography, Ion Exchange; Citrates; Cross Reactions; Dicumarol; Electrophoresis, Disc; Enzyme Activation; Epitopes; Immunoelectrophoresis; Male; Prothrombin; Rabbits; Vitamin K

Topics: Amino Acids; Animals; Binding Sites; Blood Coagulation Disorders; Calcium; Carbohydrates; Cattle; Chromatography, Gel; Chromatography, Ion Exchange; Dicumarol; Electrophoresis, Disc; Enzyme Activation; Factor X; Female; Hydrogen-Ion Concentration; Precipitin Tests; Prothrombin; Rabbits; Snakes; Spectrophotometry, Ultraviolet; Trypsin; Venoms; Vitamin K

Topics: Alkylation; Amino Acids; Animals; Blood Coagulation Disorders; Calcium; Carbohydrates; Cattle; Chemical Phenomena; Chemistry; Cyanogen Bromide; Dicumarol; Electrophoresis, Polyacrylamide Gel; Epitopes; Immunodiffusion; Isoelectric Focusing; Molecular Weight; Peptides; Protein Binding; Protein Conformation; Prothrombin; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet; Sulfhydryl Compounds; Tyrosine; Ultracentrifugation; Vitamin K

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: Anticoagulants; Blood Coagulation Disorders; Chloramphenicol; Coumarins; Drug Interactions; Glucagon; Humans; Models, Biological; Neomycin; Phenylbutazone; Protein Binding; Quinidine; Vitamin K

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Coumarins; Factor X; Humans; Italy; Thromboplastin; Vitamin K

Topics: Animals; Blood Coagulation Disorders; Blood Coagulation Factors; Cats; Factor IX; Factor V; Factor VII; Factor VIII; Factor X; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Liver; Liver Function Tests; Maternal-Fetal Exchange; Phenytoin; Pregnancy; Prothrombin Time; Thromboplastin; Vitamin K; Warfarin

Topics: Anticonvulsants; Blood Coagulation Disorders; Epilepsy; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Maternal-Fetal Exchange; Melena; Pregnancy; Pregnancy Complications; Vitamin K

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Humans; Vitamin K

Topics: Afibrinogenemia; Blood Coagulation Disorders; Blood Coagulation Factors; Factor IX; Factor VII; Factor VIII; Factor X; Factor XIII; Fibrin; Fibrinogen; Hemophilia A; Hemophilia B; Humans; Prothrombin; Thrombin; Vitamin K

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelet Disorders; Brain Damage, Chronic; Factor V; Factor VII; Female; Fibrinogen; Fibrinolysis; Germany, West; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications; Prothrombin; Prothrombin Time; Retrospective Studies; Vitamin K; Vitamin K Deficiency Bleeding

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: Age Factors; Blood Coagulation Disorders; Gestational Age; Humans; Indicators and Reagents; Infant, Newborn; Infant, Premature; Mass Screening; Prothrombin Time; Vitamin K

Topics: Blood Coagulation Disorders; Drug-Related Side Effects and Adverse Reactions; Hemostasis; Humans; Iatrogenic Disease; Liver; Pharmacogenetics; Sex Factors; Vitamin K

Topics: Adipose Tissue; Blood Coagulation Disorders; Brain Diseases; Fatty Liver; Female; Hepatitis; Humans; Infant; Kidney Diseases; Virus Diseases; Vitamin K

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelet Disorders; Consanguinity; Diagnosis, Differential; Factor XIII; Female; Hemorrhage; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Umbilical Cord; Vitamin K; Vitamin K Deficiency Bleeding

Topics: Blood Coagulation Disorders; Blood Transfusion; Exchange Transfusion, Whole Blood; Female; Gastrointestinal Hemorrhage; Hemoperitoneum; Humans; Infant, Newborn; Infant, Newborn, Diseases; Laparotomy; Liver; Prothrombin Time; Rupture; Vitamin K

Topics: Aminocaproates; Blood Coagulation Disorders; Blood Transfusion; Duodenal Ulcer; Esophageal and Gastric Varices; Esophagitis; Fibrinogen; Fibrinolysis; Gastritis; Gastrointestinal Hemorrhage; Heparin; Humans; Liver Diseases; Phosphorus Isotopes; Portacaval Shunt, Surgical; Stomach Ulcer; Therapeutic Irrigation; Vasopressins; Vitamin K

Topics: Acenocoumarol; Acute Disease; Blood Coagulation Disorders; Chemical and Drug Induced Liver Injury; Child, Preschool; Factor VII; Factor VIII; Factor X; Hemorrhage; Humans; Kidney Diseases; Kidney Function Tests; Liver Function Tests; Male; Medication Errors; Prothrombin; Prothrombin Time; Vitamin K

Topics: Adipose Tissue; Blood Coagulation Disorders; Brain Diseases; Child, Preschool; Fatty Liver; Glucose; Hepatitis; Humans; Insulin; Kidney Diseases; Male; Mannitol; Peritoneal Dialysis; Remission, Spontaneous; Vitamin K

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Proteins; Calcium; Dicumarol; Fibrinolysis; Fibrinolytic Agents; Humans; Lipoproteins; Streptokinase; Thrombosis; Vitamin K

Topics: Adolescent; Adult; Anticonvulsants; Barbiturates; Blood Coagulation Disorders; Blood Coagulation Tests; Epilepsy; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Middle Aged; Phenytoin; Pregnancy; Pregnancy Complications; Vitamin K

Topics: Adult; Anticoagulants; Blood Coagulation Disorders; Coumarins; Humans; Male; Myocardial Infarction; Suicide; Time Factors; Vitamin K

Topics: Anti-Bacterial Agents; Blood Cell Count; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Child; Cystic Fibrosis; Fibrinolysis; Gastrointestinal Hemorrhage; Hemoptysis; Hepatomegaly; Humans; Liver; Liver Function Tests; Lung; Prospective Studies; Prothrombin Time; Splenomegaly; Thrombocytopenia; Thromboplastin; Vitamin K

Topics: Binding Sites; Blood Coagulation; Blood Coagulation Disorders; Calcium; Factor VIII; Humans; In Vitro Techniques; Protein Binding; Prothrombin; Thrombin; Thromboplastin; Vitamin K

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: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Child; Female; Hematuria; Humans; Hypoprothrombinemias; Lupus Erythematosus, Systemic; Prednisone; Prothrombin; Prothrombin Time; Thromboplastin; Vitamin K

Topics: Birth Weight; Blood Coagulation; Blood Coagulation Disorders; Blood Platelets; Humans; Infant, Newborn; Infant, Newborn, Diseases; Vitamin K; Vitamin K Deficiency Bleeding

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: Blood Coagulation Disorders; Blood Coagulation Tests; Cholestasis; Factor IX; Factor VII; Factor X; Factor XII; Humans; Preoperative Care; Thrombelastography; Time Factors; Vitamin K

Topics: Adult; Aged; Aorta, Abdominal; Aortic Aneurysm; Arthritis; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Endarteritis; Female; Humans; Leg; Male; Mesenteric Arteries; Polyarteritis Nodosa; Pseudomonas aeruginosa; Radiography, Thoracic; Skin Diseases, Infectious; Staphylococcus; Streptococcus pyogenes; Vitamin K

Topics: Antifibrinolytic Agents; Ascorbic Acid; Blood Coagulation Disorders; Hemostatics; Humans; Liver Cirrhosis; Vitamin K

Topics: Ambulatory Care; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Tests; Drug Antagonism; Drug Synergism; Humans; Medication Systems, Hospital; Thromboembolism; Vitamin K

Topics: Anticoagulants; Antithrombin III; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelet Disorders; Factor IX; Factor VII; Factor X; Fibrinogen; Hemostasis; Heparin; Humans; Prothrombin; Thrombelastography; Thrombin; Thromboplastin; Thrombosis; Vitamin K

Topics: Adolescent; Adult; Aged; Antithrombins; Blood Coagulation Disorders; Blood Coagulation Factors; Child; Factor V; Factor VII; Fibrinogen; Gastrectomy; Humans; Middle Aged; Postoperative Care; Preoperative Care; Prothrombin; Prothrombin Time; Surgical Wound Dehiscence; Vitamin K

Topics: Angiography; Blood Chemical Analysis; Blood Coagulation Disorders; Blood Platelets; Cardiac Catheterization; Electrocardiography; Fibrinolytic Agents; Heparin; Humans; Middle Aged; Pulmonary Embolism; Radionuclide Imaging; Resuscitation; Thromboembolism; Venoms; Vitamin K

Topics: Birth Weight; Blood Coagulation Disorders; Blood Coagulation Tests; Cerebral Hemorrhage; Gestational Age; Humans; Infant Mortality; Infant, Newborn; Infant, Newborn, Diseases; Vitamin K

Topics: Aged; Animals; Antidotes; Blood Coagulation Disorders; Child, Preschool; Chromatography; Coumarins; Dicumarol; Female; Humans; Male; Pedigree; Pharmacogenetics; Protein Binding; Prothrombin Time; Rabbits; Rats; Vitamin K; Vitamin K 1; Warfarin

Topics: Angina Pectoris; Anticoagulants; Blood Coagulation Disorders; Drug Synergism; Ethanol; Female; Follow-Up Studies; Heart Failure; Humans; Long-Term Care; Male; Myocardial Infarction; Vitamin K

Topics: Adult; Blood Coagulation Disorders; Cathartics; Factor VII; Female; Humans; Infusions, Parenteral; Prothrombin; Substance-Related Disorders; Vitamin K

Topics: Birth Injuries; Blood Coagulation Disorders; Blood Transfusion; Female; Hemorrhage; Humans; Infant, Newborn; Infant, Newborn, Diseases; Obstetric Labor Complications; Pregnancy; Scalp; Sex Factors; Vitamin K

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

Topics: Adolescent; Adult; Atrophy; Blood Coagulation Disorders; Blood Coagulation Tests; Child; Hepatitis A; Humans; Liver Diseases; Liver Extracts; Male; Prednisone; Vitamin K

Topics: Autopsy; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Transfusion; Female; Fetal Diseases; Fibrinogen; Hemoperitoneum; Hemorrhage; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Infusions, Parenteral; Penicillins; Pregnancy; Punctures; Respiration, Artificial; Vitamin K

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Hemorrhagic Disorders; Humans; Infant, Newborn; Infant, Newborn, Diseases; Vitamin K; Vitamin K Deficiency Bleeding

Topics: Animals; Bites and Stings; Blood Coagulation Disorders; Blood Transfusion; Calcium; Dog Diseases; Dogs; Female; Rats; Vitamin K

Topics: Animals; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Cortisone; Endotoxins; Fibrinogen; Iodine Isotopes; Kidney Glomerulus; Leukocytes; Nitrogen Mustard Compounds; Rabbits; Vitamin K; Warfarin

Topics: Blood Coagulation Disorders; Cardiac Surgical Procedures; Diagnosis, Differential; Extracorporeal Circulation; Hemorrhagic Disorders; Humans; Plasma; Postoperative Complications; Protamines; Vitamin K

Topics: Blood Coagulation Disorders; Dentistry; Oral Hemorrhage; Surgery, Oral; Vitamin K

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Blood Transfusion; Factor VII; Fibrinogen; Fibrinolysis; Humans; Immunosuppressive Agents; Steroids; Vitamin K; Vitamin K Deficiency

Topics: Aging; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelet Disorders; Blood Platelets; Blood Preservation; Blood Specimen Collection; Blood Transfusion; Exchange Transfusion, Whole Blood; Humans; Isoantibodies; Plasmapheresis; Thrombocythemia, Essential; Thrombocytopenia; Vitamin K

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Humans; Propylthiouracil; Prothrombin; Salicylates; Vitamin K; Vitamin K Deficiency

Topics: Blood Coagulation Disorders; Child; Glucocorticoids; Hemorrhagic Disorders; Humans; Thrombocytopenia; Vitamin K

Topics: Antifibrinolytic Agents; Aprotinin; Blood Coagulation Disorders; Blood Coagulation Factors; Fibrinolysis; Humans; Thrombin; Uremia; Vitamin K; Vitamin K Deficiency

Topics: Blood Coagulation Disorders; Factor V; Factor VII; Factor X; Hemorrhage; Humans; In Vitro Techniques; Liver Cirrhosis; Prothrombin; Vitamin K

Topics: Blood Coagulation Disorders; Humans; Infant, Newborn; Vitamin K; Vitamin K Deficiency Bleeding

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: Blood Coagulation Disorders; Blood Transfusion; Chemical and Drug Induced Liver Injury; Hemorrhage; Hepatitis; Hepatitis A; Humans; Jaundice; Liver; Liver Diseases; Prothrombin Time; Surgical Procedures, Operative; Transplantation; Vitamin K

Topics: Blood Coagulation Disorders; Diet; Food Irradiation; Hemorrhagic Disorders; Meat; Methionine; Naphthoquinones; Prothrombin Time; Research; Toxicology; Vitamin K; Vitamin K 3

Topics: Blood Coagulation Disorders; Child, Preschool; Female; Humans; Rocky Mountain Spotted Fever; Thrombocytopenia; Vitamin K; Vitamin K Deficiency

Topics: Aminocaproates; Aminocaproic Acid; Aprotinin; Blood Coagulation; Blood Coagulation Disorders; Blood Platelets; Deoxyribonuclease I; Dicumarol; Enzyme Inhibitors; Fibrinolysin; Fibrinolysis; Hemorrhagic Disorders; Heparin; Humans; Kallikreins; Physiology; Plasminogen; Prothrombin; Purpura; Streptodornase and Streptokinase; Streptokinase; Thrombin; Trypsin; Vitamin K; Waterhouse-Friderichsen Syndrome

Topics: Adult; Aged; Anticoagulants; Blood Coagulation Disorders; Coumarins; Humans; Middle Aged; Phenindione; Vitamin K

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Burns; Heparin; Humans; Thrombophlebitis; Vitamin K

Topics: Animals; Blood Coagulation Disorders; Blood Coagulation Factors; Dogs; Esophageal Fistula; Factor IX; Factor V; Factor VIII; Factor X; Fibrinogen; Hematocrit; Lymph; Prothrombin Time; Research; Thoracic Duct; Thromboplastin; Vitamin K

Topics: Antifibrinolytic Agents; Blood Coagulation Disorders; Female; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Postpartum Period; Pregnancy; Prenatal Care; Prothrombin; Retinal Hemorrhage; Vitamin K

Topics: Blood Coagulation; Blood Coagulation Disorders; Hemostatics; Humans; Leptospirosis; Vitamin K

Topics: Animals; Blood Coagulation; Blood Coagulation Disorders; Ethionine; Heparin Antagonists; Pancreatitis; Rats; Vitamin K

Topics: Antifibrinolytic Agents; Blood; Blood Coagulation Disorders; Dicumarol; Heparin Antagonists; Humans; Vitamin K; Vitamin K Deficiency