vitamin-k-semiquinone-radical and Hemorrhagic-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

Topics: Abdominal Pain; Acute Disease; Ankle Injuries; Arthralgia; Aspirin; Child; Consciousness Disorders; Diagnosis, Differential; Fatigue; Female; Hemorrhagic Disorders; Humans; Hyperammonemia; Hypoglycemia; Hypotension; Lactulose; Liver Failure; Reye Syndrome; Rheumatic Fever; Vitamin K

On of the most common, and serious, complications in cardiac surgery is postoperative bleeding. According to the majority of studies, between 10% and 92% of patients subjected to elective surgery require transfusions of blood products and blood derivatives. Transfusions and reinterventions are associated with longer stays in critical care units and a decrease in survival rates. There have been some important changes in the treatment of changes in haemostasis and post-surgical bleeding in the last few years, particularly with the introduction into clinical practice of working procedures backed up by clinical guidelines, as well as the appearance of new drugs. The aim of this work is to describe the main characteristics and update the use of prothrombin complexes that are currently available in Spain, with special emphasis on their use in cardiac surgery.

Topics: Anticoagulants; Blood Coagulation Factors; Blood Loss, Surgical; Blood-Borne Pathogens; Cardiac Surgical Procedures; Contraindications; Disease Transmission, Infectious; Drug Contamination; Drug Costs; Heart Diseases; Hemorrhagic Disorders; Hemostatics; Humans; Postoperative Hemorrhage; Preanesthetic Medication; Thrombophilia; Thrombosis; Vitamin K

Topics: Anticoagulants; Blood Platelets; Disease Susceptibility; Factor XII; Feedback, Physiological; Fibrinolysis; Hemorrhagic Disorders; Hemostasis; Hemostatic Disorders; Hemostatics; Humans; Thrombosis; Vitamin K

Disturbances in hemostasis are common complications of kidney diseases. Both bleeding diathesis and thromboembolism may complicate the course of chronic uremia. As far as we know, there is a limited data about protein Z in kidney disease.. The aim of our work was to examine plasma protein Z and vitamin K concentrations in nephrotic syndrome (n = 34), glomerulonephritis (n = 48), kidney transplant recipients (n = 80), peritoneally dialyzed patients (n = 42) and in the healthy volunteers (n = 27).. Vitamin K was significantly lower in nephrotic syndrome when compared to non-nephrotic patients, CAPD and healthy volunteers (p < 0.05). Protein Z was the highest in CAPD and kidney transplant recipients when compared to any other group. In nephrotic syndrome protein Z was significantly lower when compared to the healthy volunteers, but it did not differ significantly between two groups of patients with chronic renal failure (with and without nephrotic syndrome). Protein Z correlated only with fibrinogen in CAPD, glomerulonephritis and nephrotic patients. Vitamin K correlated with age and albumin in patients with glomerulonephritis, nephrotic syndrome as well as with albumin in CAPD.. Alterations in protein Z might contribute to the enhanced risk of thromboembolic complications in nephrotic syndrome, CAPD and Tx via different and unknown mechanisms. This phenomenon seems to be unrelated to vitamin K status in these patients.

Topics: Adult; Blood Proteins; Case-Control Studies; Female; Glomerulonephritis; Hemorrhagic Disorders; Humans; Kidney Transplantation; Male; Middle Aged; Nephrotic Syndrome; Peritoneal Dialysis; Risk Factors; Thromboembolism; Vitamin K

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

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

Topics: Administration, Oral; Adult; Animals; Anticoagulants; Coumarins; Drug Eruptions; Drug Hypersensitivity; Female; Fibrinolytic Agents; Hemorrhagic Disorders; Heparin; Humans; Male; Osteoporosis; Pregnancy; Pregnancy Complications, Cardiovascular; Risk Factors; Thrombocytopenia; Thrombolytic Therapy; Vitamin K

For the attention of psychiatric consultants, brodifacoum, a new longer-acting, warfarin-like oral anticoagulant rodenticide, has been used for suicide attempts. The overdose potential with brodifacoum is serious since it is readily available without prescription, and bleeding complications last for weeks to months after a single ingestion. This article reports a case of ingestion and reviews four similar cases from medical literature. Also reviewed are details about mechanism of action, procedures for diagnosis, and treatment requirements. Also, characteristics of persons who ingest long-acting anticoagulants appear to differ from those who ingest short-acting anticoagulants reported from earlier literature.

Topics: 4-Hydroxycoumarins; Anticoagulants; Factitious Disorders; Hemorrhagic Disorders; Humans; Male; Middle Aged; Rodenticides; Suicide, Attempted; Vitamin K

Topics: Anti-Bacterial Agents; Anticoagulants; Bacterial Infections; Drug Synergism; Hemorrhage; Hemorrhagic Disorders; Hemostasis; Humans; Platelet Adhesiveness; Platelet Aggregation; Prothrombin Time; Thrombocytopenia; Vitamin K

Topics: Animals; Ascorbic Acid; Blood Coagulation; Blood Coagulation Factors; Chemical Phenomena; Chemistry; Factor IX; Factor VII; Factor VIII; Hemorrhagic Disorders; Hemostasis; Humans; Hypoprothrombinemias; Oxidation-Reduction; Prothrombin Time; Thrombin; Vitamin K; Vitamins

Topics: Aminocaproates; Aprotinin; Blood Coagulation Tests; Fibrinogen; Hemorrhage; Hemorrhagic Disorders; Heparin; 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

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

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

Topics: Administration, Oral; Adult; Animals; Anticoagulants; Coumarins; Drug Eruptions; Drug Hypersensitivity; Female; Fibrinolytic Agents; Hemorrhagic Disorders; Heparin; Humans; Male; Osteoporosis; Pregnancy; Pregnancy Complications, Cardiovascular; Risk Factors; Thrombocytopenia; Thrombolytic Therapy; Vitamin K

Factor V inhibitors are a rare cause of life-threatening bleeding. We present a case of an acquired factor V inhibitor likely caused by coronavirus disease 2019 infection. Bleeding was manifested by severe anemia requiring frequent red-cell transfusion, left psoas muscle hematoma, and left retroperitoneal cavity hematoma. Factor V activity was less than 1% and the factor V inhibitor titer was 31.6 Bethesda units. Severe acute respiratory syndrome coronavirus 2 RNA testing of the nasopharynx was positive 2 weeks before presentation and continued to be positive for 30 days. The patient failed treatment with intravenous immunoglobulin and dexamethasone. Three cycles of plasmapheresis with fresh frozen plasma replacement resulted in correction of the bleeding and laboratory coagulopathy. This is the first reported case of a factor V inhibitor in a coronavirus disease 2019 patient and suggests that plasmapheresis may be a successful treatment strategy.

Topics: Aged, 80 and over; Anemia; Antibodies, Viral; Antibody Specificity; Autoantibodies; Combined Modality Therapy; Comorbidity; COVID-19; Delayed Diagnosis; Dexamethasone; Erythrocyte Transfusion; Factor V; Female; Hematoma; Hemorrhagic Disorders; Humans; Immunoglobulins, Intravenous; Lupus Coagulation Inhibitor; Octreotide; Plasma; Plasmapheresis; SARS-CoV-2; Vitamin K

γ-Glutamyl carboxylase (GGCX) is an integral membrane protein that catalyzes posttranslational carboxylation of a number of vitamin K-dependent (VKD) proteins involved in a wide variety of physiologic processes, including blood coagulation, vascular calcification, and bone metabolism. Naturally occurring GGCX mutations are associated with multiple distinct clinical phenotypes. However, the genotype-phenotype correlation of GGCX remains elusive. Here, we systematically examined the effect of all naturally occurring GGCX mutations on the carboxylation of 3 structure-function distinct VKD proteins in a cellular environment. GGCX mutations were transiently introduced into GGCX-deficient human embryonic kidney 293 cells stably expressing chimeric coagulation factor, matrix Gla protein (MGP), or osteocalcin as VKD reporter proteins, and then the carboxylation efficiency of these reporter proteins was evaluated. Our results show that GGCX mutations differentially affect the carboxylation of these reporter proteins and the efficiency of using vitamin K as a cofactor. Carboxylation of these reporter proteins by a C-terminal truncation mutation (R704X) implies that GGCX's C terminus plays a critical role in the binding of osteocalcin but not in the binding of coagulation factors and MGP. This has been confirmed by probing the protein-protein interaction between GGCX and its protein substrates in live cells using bimolecular fluorescence complementation and chemical cross-linking assays. Additionally, using a minigene splicing assay, we demonstrated that several GGCX missense mutations affect GGCX's pre-messenger RNA splicing rather than altering the corresponding amino acid residues. Results from this study interpreted the correlation of GGCX's genotype and its clinical phenotypes and clarified why vitamin K administration rectified bleeding disorders but not nonbleeding disorders.

Topics: Amino Acid Sequence; Base Sequence; Calcium-Binding Proteins; Carbon-Carbon Ligases; Carboxy-Lyases; Extracellular Matrix Proteins; Genes, Reporter; Genetic Association Studies; Genetic Pleiotropy; HEK293 Cells; Hemorrhagic Disorders; Humans; Matrix Gla Protein; Mutation; Mutation, Missense; Osteocalcin; Protein C; Protein Domains; Protein Interaction Mapping; Protein Isoforms; Protein Processing, Post-Translational; Recombinant Fusion Proteins; RNA Precursors; RNA Splicing; Structure-Activity Relationship; Vitamin K

Drug-induced bleeding disorders contribute to substantial morbidity and mortality. Antithrombotic agents that cause unintended bleeding of obvious cause are relatively easy to control. However, the mechanisms of most drug-induced bleeding disorders are poorly understood, which makes intervention more difficult. As most bleeding disorders are associated with the dysfunction of coagulation factors, we adapted our recently established cell-based assay to identify drugs that affect the biosynthesis of active vitamin K-dependent (VKD) coagulation factors with possible adverse off-target results. The National Institutes of Health (NIH) Clinical Collection (NCC) library containing 727 drugs was screened, and 9 drugs were identified, including the most commonly prescribed anticoagulant warfarin. Bleeding complications associated with most of these drugs have been clinically reported, but the pathogenic mechanisms remain unclear. Further characterization of the 9 top-hit drugs on the inhibition of VKD carboxylation suggests that warfarin, lansoprazole, and nitazoxanide mainly target vitamin K epoxide reductase (VKOR), whereas idebenone, clofazimine, and AM404 mainly target vitamin K reductase (VKR) in vitamin K redox cycling. The other 3 drugs mainly affect vitamin K availability within the cells. The molecular mechanisms underlying the inactivation of VKOR and VKR by these drugs are clarified. Results from both cell-based and animal model studies suggest that the anticoagulation effect of drugs that target VKOR, but not VKR, can be rescued by the administration of vitamin K. These findings provide insights into the prevention and management of drug-induced bleeding disorders. The established cell-based, high-throughput screening approach provides a powerful tool for identifying new vitamin K antagonists that function as anticoagulants.

Topics: 4-Hydroxycoumarins; Animals; Anticoagulants; Blood Coagulation; Cell Culture Techniques; Drug Evaluation, Preclinical; HEK293 Cells; Hemorrhagic Disorders; Hep G2 Cells; High-Throughput Screening Assays; Humans; Indenes; Male; Metabolic Networks and Pathways; Mice; Mice, Inbred BALB C; Off-Label Use; Vitamin K; Vitamin K Epoxide Reductases

Topics: Blood Coagulation Factors; Carbon-Carbon Ligases; CRISPR-Cas Systems; Dose-Response Relationship, Drug; Frameshift Mutation; Gene Knockout Techniques; Genes, Reporter; HEK293 Cells; Hemorrhagic Disorders; Humans; Introns; Protein Binding; Protein Domains; Protein Processing, Post-Translational; Protein Stability; RNA Splicing; Sequence Deletion; Vitamin K

Very premature infants are at high risk of bleeding complications; however, few data exist on ranges for standard coagulation tests.. The primary objective of this study was to measure standard plasma coagulation tests and thrombin generation in very premature infants compared with term infants. The secondary objective was to evaluate whether an association existed between coagulation indices and intraventricular hemorrhage (IVH).. Cord and peripheral blood of neonates < 30 weeks gestational age (GA) was drawn at birth, on days 1 and 3 and fortnightly until 30 weeks corrected gestational age. Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen and coagulation factor levels were measured and tissue factor-stimulated thrombin generation was characterized. Control plasma was obtained from cord blood of term neonates.. One hundred and sixteen infants were recruited. Median (range) GA was 27.7 (23.7-29.9) weeks and mean (SD) birth weight was 1020 (255) g. Median (5th-95th percentile) day 1 PT, APTT and fibrinogen were 17.5 (12.7-26.6) s, 78.7 (48.7-134.3) s and 1.4 (0.72-3.8) g L(-1) , respectively. No difference in endogenous thrombin potential between preterm and term plasma was observed, where samples were available. Levels of coagulation factors II, VII, IX and X, protein C, protein S and antithrombin were reduced in preterm compared with term plasma. Day 1 APTT and PT were not associated with IVH.. In the largest cross-sectional study to date of very preterm infants, typical ranges for standard coagulation tests were determined. Despite long clotting times, thrombin generation was observed to be similar in very preterm and term infants.

Topics: Blood Coagulation Factors; Blood Coagulation Tests; Blood Component Transfusion; Cerebral Ventricles; Cross-Sectional Studies; Female; Fetal Blood; Fibrinogen; Gestational Age; Hemorrhagic Disorders; Humans; Infant, Newborn; Infant, Premature; Infant, Small for Gestational Age; Intensive Care, Neonatal; Intracranial Hemorrhages; Male; Partial Thromboplastin Time; Prospective Studies; Prothrombin Time; Recombinant Proteins; Reference Standards; Thrombin; Thromboplastin; Vitamin K

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

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

Topics: Anticoagulants; Blood Coagulation Factors; Factor IX; Factor VII; Factor VIIa; Factor X; Hemorrhagic Disorders; Humans; Prothrombin; Recombinant Proteins; Vitamin K

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

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

Topics: Hemorrhagic Disorders; Humans; Mixed Function Oxygenases; Protein S; Vitamin K; Vitamin K Epoxide Reductases

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

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

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

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

Familial multiple coagulation factor deficiency (FMFD) of factors II, VII, IX, X, protein C, and protein S is a very rare bleeding disorder with autosomal recessive inheritance. The phenotypic presentation is variable with respect to the residual activities of the affected proteins, its response to oral administration of vitamin K, and to the involvement of skeletal abnormalities. The disease may result either from a defective resorption/transport of vitamin K to the liver, or from a mutation in one of the genes encoding gamma-carboxylase or other proteins of the vitamin K cycle. We have recently presented clinical details of a Lebanese family and a German family with 10 and 4 individuals, respectively, where we proposed autosomal recessive inheritance of the FMFD phenotype. Biochemical investigations of vitamin K components in patients' serum showed a significantly increased level of vitamin K epoxide, thus suggesting a defect in one of the subunits of the vitamin K 2,3-epoxide reductase (VKOR) complex. We now have performed a genome-wide linkage analysis and found significant linkage of FMFD to chromosome 16. A total maximum 2-point LOD score of 3.4 at theta = 0 was obtained in the interval between markers D16S3131 on 16p12 and D16S419 on 16q21. In both families, patients were autozygous for 26 and 28 markers, respectively, in an interval of 3 centimorgans (cM). Assuming that FMFD and warfarin resistance are allelic, conserved synteny between human and mouse linkage groups would restrict the candidate gene interval to the centromeric region of the short arm of chromosome 16.

Topics: Animals; Blood Coagulation Factors; Centromere; Child; Chromosome Mapping; Chromosomes, Human, Pair 16; DNA Mutational Analysis; Drug Resistance; Female; Genes, Recessive; Genetic Markers; Genotype; Germany; Glutathione Transferase; Hemorrhagic Disorders; Humans; Infant, Newborn; Lebanon; Lod Score; Male; Mice; Microsatellite Repeats; Mixed Function Oxygenases; Multienzyme Complexes; Pedigree; Rats; Species Specificity; Vitamin K; Vitamin K 1; Vitamin K Epoxide Reductases; Warfarin

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

A 4-year-old Holstein cow from a farm where 2 cows had recently died suddenly was referred for evaluation of acute severe colic. Right flank laparotomy revealed a large mesenteric hematoma. Within 14 layer chromatographic analyses of the moldy hay and blood from the necropsied cow and the hospitalized cow were positive for dicumarol. A diagnosis of sweet vernal poisoning was confirmed on the basis of clinical and toxicologic findings. The cow was treated with supportive therapy, blood transfusions, and vitamin K1 and recovered without complications. Because sweet vernal grass is becoming common in certain areas and the use of round bales is commonplace, practitioners should be aware of the potential for this toxicosis.

Topics: Abdomen; Animals; Anticoagulants; Blood Gas Analysis; Blood Transfusion; Cattle; Cattle Diseases; Chromatography, Thin Layer; Colic; Diagnosis, Differential; Dicumarol; Female; Fluid Therapy; Hematoma; Hemophilia B; Hemorrhagic Disorders; Partial Thromboplastin Time; Plant Poisoning; Poaceae; Pregnancy; Prothrombin Time; Ultrasonography; Vitamin K

The reasons for the decreased functional activity of prothrombin in liver diseases are still speculative. When a highly purified preparation of prothrombin from a patient with liver cirrhosis is available, the cause of prothrombin abnormalities may be researched on a molecular basis. In this study, prothrombin (6.7 mg) was purified from the ascites fluid (1130 mL) of a patient with liver cirrhosis by barium citrate adsorption, ammonium sulfate elution, DEAE Sephacel and Heparin Sepharose CL-6B column chromatography steps. The molecular weight of this prothrombin was the same as that of normal prothrombin purified from a normal plasma pool. The specific activities were found to be 3.36 U/mg in the one stage clotting assay and 28.9 U/mg in the staphylocoagulase/chromogenic substrate assay, while the normal prothrombin specific activities were 3.92 U/mg and 30.1 U/mg respectively. When N-terminal amino acid sequence analysis was carried out, it was seen that the first 20 residues were identical to the normal human prothrombin excepting the Gla at position #14.

Topics: 1-Carboxyglutamic Acid; Amino Acid Sequence; Ascitic Fluid; Glutamic Acid; Hemorrhagic Disorders; Humans; Liver Cirrhosis; Molecular Weight; Protein Processing, Post-Translational; Prothrombin; Prothrombin Time; Vitamin K

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

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

A 76-year-old man under long term oral anticoagulant treatment showed unclottable prothrombin time (PT) without overt bleeding. After oral administration of vitamin K1, PT remained severely prolonged and the patient was hospitalized. INR was 8.0 and responded to parenteral vitamin K. Cholestasis resulting in poor intestinal vitamin K resorption was assumed to have caused "overanticoagulation". Quick test is a global clotting test for the extrinsic and common pathways of the coagulation system. Increased PT, i.e. decreased Quick percentage, may be due to different conditions and should--if unexplained--be further analyzed by assaying factors II, V, VII, X and fibrinogen. Preanalytical problems, plasma dilution with clotting factor-free volume replacement, decreased vitamin K-dependent clotting factors (oral anticoagulation, intoxication with certain rodenticides, vitamin K deficiency), impaired liver synthetic capacity, disseminated intravascular coagulation, or massive heparin contamination may cause prolonged PT. Newborns physiologically have longer PT and should receive vitamin K prophylaxis.

Topics: Administration, Oral; Aged; Anticoagulants; Blood Coagulation Tests; Cholestasis, Intrahepatic; Diagnosis, Differential; Heart Valve Prosthesis Implantation; Hemorrhagic Disorders; Humans; International Normalized Ratio; Male; Phenprocoumon; Postoperative Complications; Vitamin K

We describe the case of a 22 yr old male patient with cystic fibrosis, who, after long-term antibiotic treatment of pulmonary infection, developed a haemorrhagic diathesis with severe bleeding from the mucus membrane of the mouth, and haematuria. Rapid recovery was observed after infusion of vitamin K. During 8 months of follow-up, no evidence of recurrence of the clotting disturbances and anaemia were noted. The combination of impaired absorption of vitamin K due to underlying disease with the antibiotic-induced suppression of vitamin K synthesis by intestinal bacteria could be a possible explanation for this disorder.

Topics: Adult; Cefuroxime; Cephalosporins; Cystic Fibrosis; Follow-Up Studies; Gentamicins; Hemorrhagic Disorders; Humans; Male; Netilmicin; Pneumonia; Time Factors; 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

Hemorrhagic diathesis developed 4 hr after a bite by one fang of a two-month-old specimen of Bothrops asper. Severe allergy to horse serum contraindicated the use of horse antivenom, and a substitution therapy was started 20 hr after the bite. During the following 4 days the patient was treated with infusions of 8 g human fibrinogen, 2500 U of cryoprecipitate, 1000 ml of human plasma and vitamin K in several portions. By means of plasmapheresis 1800 ml of plasma was exchanged. Until plasmapheresis on the third day the treatment resulted in short remission and diminution of the spontaneous bleeding, which ceased on the 5th day. Coagulation tests relevant to disseminated intravascular coagulation and consumption coagulopathy were performed for 12 days. Fibrinogen levels started to rise on the 8th day and normalized 12 days after the bite. Analysis of the venoms from juvenile and adult Bothrops asper snakes revealed that the former has a strong prothrombin-converting activity, the latter contained mainly a thrombin-like, fibrinogen-converting enzyme.

Topics: Age Factors; Animals; Antivenins; Blood Coagulation; Combined Modality Therapy; Contraindications; Crotalid Venoms; Fibrinogen; Hemorrhagic Disorders; Humans; Infusions, Intravenous; Middle Aged; Plasmapheresis; Snake Bites; 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

Five patients with known bleeding diatheses were treated with extracorporeal shock wave lithotripsy. Specific therapy was administered before extracorporeal shock wave lithotripsy to reverse the bleeding disorder. After treatment each patient was monitored with serial hemoglobin determinations and renal ultrasonography. The course during and after lithotripsy was uneventful in all patients. We conclude that extracorporeal shock wave lithotripsy is a viable option for patients with significant bleeding diatheses provided that specific therapy to reverse the coagulopathic condition is available and used before treatment.

Topics: Female; Hemorrhagic Disorders; Humans; Lithotripsy; Male; Plasma; Prothrombin Time; Risk Factors; Ureteral Calculi; Vitamin K

This paper presents a study of treatment involving vitamin K1 (VK1) accompanied by bile acids for hemorrhagic diathesis that was applied 42 times in 35 patients with decompensated liver cirrhosis. The hepaplastin test (HPT) value showed no change during the administration of VK1 alone. The HPT value elevated significantly, however, after the administration of VK1 with bile acid, especially when using ursodeoxycholic acid (UDCA). The HPT value in patients treated with VK1 in addition to UDCA before treatment with 53.2% +/- 10.2% (mean +/- SD) and after that for 2.1 +/- 1.1 months (mean +/- SD) with 74.7 +/- 16.8% showed a significant difference (p less than 0.001). On the other hand, no significant difference was noted between the HPT value of 57.2 +/- 13.6% before and that of 62.9 +/- 13.9% after the treatment in patients treated using VK1 in conjunction with chenodeoxycholic acid (CDCA). These results indicate that the therapy incorporating VK1 and bile acid, especially UDCA, is useful for reducing the hemorrhagic tendency in patients with decompensated liver cirrhosis who show no improvement using VK1 alone.

Topics: Chenodeoxycholic Acid; Deoxycholic Acid; Drug Therapy, Combination; Female; Hemorrhagic Disorders; Humans; Liver Cirrhosis; Male; Ursodeoxycholic Acid; Vitamin K

Combined deficiency of coagulant activity of the vitamin K-dependent factors was found in a 14-year-old boy suffering from severe hemorrhages. Immunoassays revealed the presence of acarboxyprothrombin. The bleedings could be controlled, but the coagulation defects persisted during more than 2 years' follow-up and could not be corrected by oral or parenteral vitamin K. No intoxication or underlying disease was found. The abnormality was considered a congenital disorder of the carboxylation of prothrombin.

Topics: Adolescent; Blood Coagulation Factors; Factor VII Deficiency; Factor X Deficiency; Follow-Up Studies; Hemophilia B; Hemorrhagic Disorders; Humans; Hypoprothrombinemias; Male; Protein Processing, Post-Translational; Prothrombin; Vitamin K

A case of moxalactam-induced coagulopathy is reported. The authors think that this coagulopathy is caused by an effect on platelet aggregation and not by inhibition of vitamin K-dependent clotting factors. It is recommended that bleeding times be routinely checked preoperatively in patients being treated with moxalactam.

Topics: Bleeding Time; Brain Abscess; Child; Drug Therapy, Combination; Hemorrhagic Disorders; Humans; Intraoperative Complications; Male; Meningitis; Moxalactam; Partial Thromboplastin Time; Platelet Aggregation; Platelet Function Tests; Prothrombin Time; Vitamin K

A case is presented of a severe bleeding diathesis associated with moxalactam administration that was confirmed on rechallenge. Potential mechanisms of action and recommendations for patient monitoring are discussed.

Topics: Hemorrhagic Disorders; Humans; Male; Middle Aged; Moxalactam; Vitamin K

Two breast fed infants had late manifestations of Vitamin K deficiency. No underlying disease was found in the first case. The second patient was found to have alpha 1-Antitrypsin deficiency (Pi type ZZ). The latter patient initially responded well to a single dose of vitamin K administered orally (3 mg). However, three weeks later, he was admitted to our hospital with severe intracranial hemorrhage due to severe vitamin K deficiency. Vitamin K requirements in infants and clinical characteristics of vitamin K deficiency in infants older than 1 week are discussed.

Topics: Blood Coagulation Tests; Breast Feeding; Cerebral Hemorrhage; Female; Hemorrhagic Disorders; Humans; Infant; Infant, Newborn; Male; Vitamin K; Vitamin K Deficiency

Topics: Cefamandole; Cephalosporins; Hemorrhagic Disorders; Humans; Hypoprothrombinemias; Prothrombin Time; Vitamin K

An outbreak of a haemorrhagic diathesis in cattle fed home produced hay is described. A similar syndrome was reproduced experimentally in calves by feeding them the hay. The experimental disease was characterised by increased prothrombin and partial thromboplastin times while the leucocyte and erythrocyte counts remained normal until the terminal haemorrhage. The calves ate well and grew well until the rapid onset of progressive weakness, stiff gait, mucosal pallor, tachycardia, tachypnoea and haematomata ending in sudden death. The absence of blood coagulation was seen at necropsy while petechial, ecchymotic and free haemorrhages were found in most organs. Particularly striking were massive ecchymotic haemorrhages on the peritoneal surface of the rumen, a bloody, gelatinous mass enveloping each kidney and extensive bruising, haemorrhage and haematomata in the subcutis of the limbs. In a second feeding trial the effects of various preparations of vitamin K1 and vitamin K3 were investigated. Oral administration of large quantities of vitamin K1 reduced the elevated prothrombin time; vitamin K3 acted less consistently. Analysis of the hay for trichothecene mycotoxins was negative but floral analysis revealed that sweet vernal grass (Anthoxanthum odoratum) comprised about 80 per cent of the hay. Dicoumarol was detected in the hay and in the serum and ruminal contents of the experimental calves. The diagnosis, treatment, control and importance of this syndrome in the United Kingdom are discussed.

Topics: Animal Feed; Animals; Cattle; Cattle Diseases; Dicumarol; Disease Outbreaks; Female; Hemorrhagic Disorders; Plant Poisoning; Prothrombin Time; Syndrome; United Kingdom; Vitamin K

Topics: Animal Diseases; Animals; Blood Coagulation; Dog Diseases; Dogs; Hemorrhagic Disorders; Indans; Rodenticides; Vitamin K; Warfarin

Topics: Abdomen, Acute; Aged; Anticoagulants; Female; Hemorrhagic Disorders; Humans; Ice; Male; Middle Aged; Myocardial Infarction; Thromboembolism; Vitamin K

A case of severe haemorrhagic diathesis due to acquired deficiency of factor X (both immunologically and in procoagulant activity) is presented. The clinical and serological features of this case indicated mycoplasma pneumonial infection. Factor X in the peripheral blood did not appear to be influenced by administration of vitamin K, prothrombin-complex concentrate, fresh plasma or fresh whole blood. Circulating inhibitors of blood coagulation were absent and systemic amyloidosis could not be demonstrated. After 20 d, factor X spontaneously returned to normal. In view of the absence of other known causes of factor X deficiency, a possible relationship with mycoplasma pneumonial infection is suggested.

Topics: Blood Transfusion; Factor X Deficiency; Hemorrhagic Disorders; Humans; Hypoprothrombinemias; Male; Middle Aged; Pneumonia, Mycoplasma; Prothrombin; Remission, Spontaneous; Vitamin K

Topics: Adult; Blood Transfusion; Exchange Transfusion, Whole Blood; Hemorrhagic Disorders; Heparin; Humans; Liver Diseases; Male; Vitamin K

Haemorrhagic diathesis was a leading symptom in diagnosing celiac disease in 4 patients. In all 4 patients, a duodenal biopsy showed total villous atrophy. Although 3 of the children were typically dystrophic, the weight of the 4th child, an 8 month old boy, was within the normal range. In this patient, who suffered from neither diarrhea nor vomiting, heavy cutaneous and mucous membrane bleeding were the only symptoms of the disease. In all 4 cases the haemorrhagic diathesis could be explained by a low prothrombin complex, whereas the rest of the coagulation tests were normal. After the administration of Vitamin K1 there was an immediate rise in the prothrombin complex and bleeding was quickly stopped. Noteworthy is that due to infections, 3 of the 4 patients, received antibiotics just before the onset of the bleeding. In celiac disease, the conversion from a K-hypovitaminosis into a K-avitaminosis by the administration of antibiotics is discussed.

Topics: Anti-Bacterial Agents; Celiac Disease; Female; Hemorrhagic Disorders; Humans; Infant; Male; Vitamin K; Vitamin K Deficiency

Disorders of coagulation are part of the clinical syndrome in hepatic failure. The pathophysiology of these disorders is discussed; analysis of coagulation defects in hepatic disorders does not help in differential diagnosis of hepatic diseases in the proper sense, but it is of considerable prognostic value. Therapy of hepatic diseases is discussed taking into account the pathophysiology of hepatic disorders; success of any therapeutic approach however is very limited, because of the bad prognosis of the underlying disease.

Topics: Antifibrinolytic Agents; Blood Coagulation Factors; Blood Platelets; Blood Transfusion; Fibrinolysis; Hemorrhagic Disorders; Heparin; Humans; Liver; Liver Diseases; Prognosis; Splenectomy; Thrombocytopenia; Vitamin K

Twenty-five patients with covert ingestion of oral anticoagulant drugs were studied. Most of the patients were women who were either connected with the medical profession or were previously treated with antigoagulants. The most common findings were ecchymoses, hematuria, and a markedly prolonged prothrombin time. The anticoagulant drug was identified in the plasma of all 25 patients. Most patients responded promptly to administration of vitamin K1. The most common motives were malingering and suicide. The world literature was reviewed for covert ingestion of oral anticoagulant drugs and 48 other cases were found. The correct diagnosis is important to focus the physician's attention on the psychiatric rather than the somatic aspects of the disorder.

Topics: Adult; Aged; Anticoagulants; Canada; Diagnosis, Differential; Europe; Female; Hemorrhagic Disorders; Humans; Hysteria; Male; Malingering; Medical Staff; Middle Aged; Prothrombin Time; Substance-Related Disorders; United States; Vitamin K

This article gives a survey of the physiology of blood coagulation in newborn infants, subdivided into the particularities of the plasmic coagulation system and the fibronolysis. Etiology, diagnosis and therapy of the consumption coagulopathy as well as the coagulopathy of production are dealed with.

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Disseminated Intravascular Coagulation; Female; Fibrinolysis; Hemorrhagic Disorders; Heparin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Liver Diseases; Microcirculation; Plasma Substitutes; Prednisolone; Pregnancy; Streptokinase; Vitamin K; Vitamin K Deficiency

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Chronic Disease; Diarrhea, Infantile; Female; Gastrointestinal Hemorrhage; Hemorrhagic Disorders; Humans; Infant; Infant, Newborn; Malabsorption Syndromes; Male; Maternal-Fetal Exchange; Pregnancy; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Asphyxia Neonatorum; Autoantibodies; Blood Coagulation Tests; Blood Platelets; Blood Transfusion; Capillary Fragility; Capillary Permeability; Cerebral Hemorrhage; Disseminated Intravascular Coagulation; Exchange Transfusion, Whole Blood; Female; Hemophilia A; Hemorrhage; Hemorrhagic Disorders; Heparin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Lung; Maternal-Fetal Exchange; Pregnancy; Thrombocytopenia; Vitamin K; Vitamin K Deficiency; von Willebrand Diseases

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

Topics: Adult; Blood Coagulation Factors; Coumarins; Female; Hemorrhage; Hemorrhagic Disorders; Humans; Male; Middle Aged; Vitamin K

Topics: Animals; Antifibrinolytic Agents; Blood Coagulation Disorders; Coagulants; Flavonoids; Hemorrhage; Hemorrhagic Disorders; Hemostatics; Humans; Purpura; Snake Venoms; Venoms; 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: Adjustment Disorders; Adult; Blood Cell Count; Coumarins; Female; Hemorrhagic Disorders; Humans; Personality Disorders; Prothrombin Time; Psychotherapy; Self Medication; Self Mutilation; Vitamin K

Topics: Cystic Fibrosis; Diet; Female; Hemoglobins; Hemorrhagic Disorders; Humans; Hypoprothrombinemias; Infant; Malabsorption Syndromes; Male; Prothrombin Time; Vitamin K; Vitamin K Deficiency

Topics: Adrenochrome; Aminocaproates; Animals; Antifibrinolytic Agents; Carbon Tetrachloride Poisoning; Cyclohexanecarboxylic Acids; Dicumarol; Ethylamines; Factor Analysis, Statistical; Hemorrhagic Disorders; Hemostatics; Hydroquinones; Male; Phenols; Rats; Semicarbazones; Sulfonic Acids; Vitamin K; Vitamin K 1

Topics: Animals; Anticoagulants; Blood Coagulation Tests; Factor IX; Factor VII; Factor X; Hemorrhagic Disorders; Humans; Methods; Prothrombin; Rabbits; Thromboembolism; Vitamin K; Vitamin K Deficiency

Topics: Adult; Anticoagulants; Female; Hemorrhagic Disorders; Humans; Necrosis; Ovarian Cysts; Rupture; Thigh; Thromboembolism; Vitamin K

Topics: Administration, Oral; Anticoagulants; Hemorrhage; Hemorrhagic Disorders; Humans; Vitamin K

Topics: Animals; Animals, Laboratory; Clostridium perfringens; Colon; Enterococcus faecalis; Escherichia coli; Factor V; Factor VII; Factor X; Female; Germ-Free Life; Hemorrhagic Disorders; Hemothorax; Ileum; Lactobacillus; Male; Mice; Myocardium; Pericardium; Proteus; Prothrombin; Rats; Rodent Diseases; Vitamin K

Topics: Acute Disease; Ascites; Ascorbic Acid; Blood Protein Disorders; Diet Therapy; Diuretics; Glucocorticoids; Hemorrhagic Disorders; Hepatic Encephalopathy; Hepatitis A; Humans; Mineralocorticoid Receptor Antagonists; Rest; Rutin; Serum Albumin; Vitamin K

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

Topics: Blood Coagulation Factors; Blood Coagulation Tests; Female; Hematoma, Subdural; Hemorrhagic Disorders; Humans; Infant; Infant, Newborn; Malabsorption Syndromes; Male; Prothrombin; Vitamin K; Vitamin K Deficiency Bleeding

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

A haemorrhagic diathesis is described in infants; this is preceded and accompanied by constitutional symptoms such as fever, diarrhoea, vomiting, anorexia, and pallor. These children had a severe coagulation abnormality, due to deficiency of vitamin-K-dependent coagulation factors, and it was corrected by administration of vitamin K. No conclusion could be drawn as to the aetiology of this condition but some possible causes are discussed.

Topics: Blood Coagulation Factors; Blood Coagulation Tests; Blood Transfusion; Female; Hemorrhagic Disorders; Humans; Infant; Male; Vitamin K; Vitamin K Deficiency

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

Topics: Adult; Anticoagulants; Coumarins; Female; Hemorrhagic Disorders; Humans; Male; Middle Aged; Prothrombin Time; Vitamin K

Topics: Blood Coagulation Tests; Hematoma; Hemophilia A; Hemorrhagic Disorders; Humans; Infant, Newborn; Infant, Newborn, Diseases; Injections, Intramuscular; Male; Vitamin K; Vitamin K Deficiency

Topics: Aminocaproates; Blood Coagulation Factors; Blood Coagulation Tests; Blood Transfusion; Diagnosis, Differential; Exchange Transfusion, Whole Blood; Fibrinogen; Hemorrhagic Disorders; Humans; Prednisone; Protamines; 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 Factors; Blood Transfusion; Drug Therapy; Gastrointestinal Hemorrhage; Hemorrhage; Hemorrhagic Disorders; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Melena; Prednisone; Thrombin; Vitamin K; Vitamin K Deficiency Bleeding

Topics: Animals; Antifibrinolytic Agents; Castration; Cattle; Food Irradiation; Hemorrhagic Disorders; Male; Meat; Metabolism; Orchiectomy; Pharmacology; Prothrombin Time; Rats; Research; Testosterone; Vitamin K; Vitamin K 3

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: Blood Coagulation Tests; Criminals; Diagnosis; Factor IX; Factor VII; Factor X; Geriatrics; Hemorrhagic Disorders; Humans; Poisoning; Prothrombin Time; Toxicology; Vitamin K; Warfarin

Topics: Animals; Anthelmintics; Ascariasis; Ascaris; Blood Coagulation Factors; Communicable Diseases; Drug Therapy; Hemorrhagic Disorders; Humans; Metabolism; Vitamin K

Topics: Antifibrinolytic Agents; Hemorrhagic Disorders; Humans; Infant, Newborn; Infant, Premature, Diseases; Vitamin K; Vitamin K 1; Vitamin K Deficiency Bleeding

Topics: Antifibrinolytic Agents; Hemorrhagic Disorders; Humans; Liver Diseases; Vascular Diseases; Vitamin K

Topics: Antifibrinolytic Agents; Hemorrhagic Disorders; Humans; Hypoprothrombinemias; Vitamin K

Topics: Antifibrinolytic Agents; Hemorrhagic Disorders; Humans; Infant; Infant, Newborn; Infant, Premature; Naphthoquinones; Vitamin K; Vitamin K Deficiency Bleeding

Topics: Antifibrinolytic Agents; Hemorrhagic Disorders; Humans; Naphthoquinones; Pregnancy; Pregnancy Complications; Vitamin K; Vitamin K Deficiency

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

Topics: Antifibrinolytic Agents; Celiac Disease; Hemorrhagic Disorders; Humans; Sprue, Tropical; Steatorrhea; Vitamin K; Vitamin K Deficiency

Topics: Antifibrinolytic Agents; Factor IX; Factor VII; Factor X; Hemorrhagic Disorders; Hemostatics; Humans; Prothrombin; Steatorrhea; Vitamin K; Vitamin K Deficiency

Topics: Antifibrinolytic Agents; Hemorrhagic Disorders; Hemostatics; Humans; Infant, Newborn; Naphthoquinones; Vitamin K; Vitamin K 1; Vitamin K Deficiency Bleeding

Topics: Erythroblastosis, Fetal; Factor X; Fetal Blood; Hematologic Diseases; Hemorrhagic Disorders; Humans; Infant, Newborn; Vitamin K; Vitamin K Deficiency Bleeding

Topics: Antifibrinolytic Agents; Hemorrhagic Disorders; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Vitamin K; Vitamins

Topics: Administration, Intravenous; Antifibrinolytic Agents; Hemolysis; Hemorrhagic Disorders; Humans; Hypoprothrombinemias; Prothrombin; Vitamin K; Vitamin K 1

Topics: Antifibrinolytic Agents; Hemorrhagic Disorders; Hypoprothrombinemias; Prothrombin; Vitamin K; Vitamin K 1; Vitamins

Topics: Child; Hemorrhagic Disorders; Humans; Hypoprothrombinemias; Infant; Infant, Newborn; Infant, Newborn, Diseases; Prothrombin; Vitamin K

Topics: Hemorrhagic Disorders; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Retinoids; Vitamin K

Topics: Antifibrinolytic Agents; Blood Coagulation Tests; Factor VII; Hemorrhagic Disorders; Humans; Infant, Newborn; Infant, Premature; Vitamin K

Topics: Antifibrinolytic Agents; Hemorrhagic Disorders; Humans; Hypoprothrombinemias; Naphthoquinones; Vitamin K; Vitamin K 1

Topics: Antifibrinolytic Agents; Factor VII; Hemorrhagic Disorders; Humans; Hypoprothrombinemias; Infant, Newborn; Naphthoquinones; Retinoids; Vitamin K; Vitamin K 1

Topics: Anticoagulants; Antifibrinolytic Agents; Hemorrhagic Disorders; Heparin Antagonists; Hypoprothrombinemias; Phenindione; Vitamin K; Vitamin K 1

Topics: Antifibrinolytic Agents; Coumarins; Dicumarol; Hemorrhagic Disorders; Heparin Antagonists; Hypoprothrombinemias; Naphthoquinones; Vitamin K; Vitamin K 1; Vitamin K 3

Topics: Antifibrinolytic Agents; Hemorrhagic Disorders; Heparin Antagonists; Hypoprothrombinemias; Naphthoquinones; Vitamin K; Vitamin K 1

Topics: Blood Coagulation; Blood Transfusion; Factor V Deficiency; Hemorrhagic Disorders; Humans; Naphthoquinones; Vitamin K

Topics: Antifibrinolytic Agents; Hemorrhage; Hemorrhagic Disorders; Humans; Hypoprothrombinemias; Prothrombin; Vitamin K

Topics: Antifibrinolytic Agents; Hemorrhage; Hemorrhagic Disorders; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Vitamin K

Topics: Antifibrinolytic Agents; Female; Hemorrhagic Disorders; Hemostatics; Humans; Infant; Infant, Newborn; Naphthoquinones; Pregnancy; Vitamin K

Topics: Antifibrinolytic Agents; Hemorrhagic Disorders; Hemostatics; Humans; Hypoprothrombinemias; Naphthoquinones; Prothrombin; Vitamin K

Topics: Antifibrinolytic Agents; Child; Hemorrhage; Hemorrhagic Disorders; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Microscopic Angioscopy; Vitamin K

Topics: Disease Susceptibility; Hemorrhagic Disorders; Hemostatics; Humans; Vitamin K; Vitamins