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 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A normally functioning hemostasis system is closely related to liver function. The liver parenchymal cells produce most of the factors and inhibitors of the clotting and fibrinolytic systems, and the RES of the liver greatly aids in the clearance of activation products. Hemostasis defects thus depend on the extent of liver damage. A wide spectrum of defects is found in patients with liver cirrhosis. Owing to impaired protein synthesis, most factors and inhibitors of the clotting and the fibrinolytic systems are markedly reduced. Additionally, abnormal vitamin K-dependent factor and fibrinogen molecules have been encountered. Most patients have hyperfibrinolysis that could be DIC in nature. Thrombocytopenia and thrombocytopathy are also found. Acute or chronic hepatocellular disease may display decreased vitamin K-dependent factor levels, especially factor VII and protein C, with other factors still being normal. If patients go into hepatic failure, the abnormalities resemble those found in liver cirrhosis. Vitamin K deficiency is associated with the production of poorly functioning vitamin K-dependent factors. All other hemostasis parameters are normal. Disturbances associated with liver surgeries again depend on the underlying liver problem. Peritoneovenous shunts (LeVeen) may lead to DIC; bleeding from partially resected liver surfaces is usually a mechanical problem. Severe bleeding is encountered with orthotopic liver transplantation. It is greatly influenced by the activation of the fibrinolytic system. This occurs during the anhepatic phase and during the reperfusion phase. The hyperfibrinolysis is mediated by an intense release of t-PA. Antifibrinolytic drugs, if used cautiously, have markedly reduced bleeding and thus reduced need for blood and blood product substitution.
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PMID:Coagulation defects in liver disease. 817 Feb 58

Clinical observations have added to the understanding of basic mechanisms of blood coagulation and its alterations in certain hemorrhagic and thrombotic states. Much clinical evidence exists for concluding that the exposure of blood to tissue factor (thromboplastin) on tissue cells represents the key event initiating fibrin clot formation after tissue injury. This then results in the formation of activated factor VII (VIIa)-tissue factor complexes, which must activate both factor X and factor IX for normal hemostasis. I describe the possible clinical consequences of an aberrant function of the natural anticoagulants regulating blood coagulation--antithrombin, protein C, and tissue factor pathway inhibitor. Understanding the physiologic function of tissue factor pathway inhibitor can illuminate why hemophilic patients bleed, but many other questions remain. I briefly review the four causes for acquired disorders of the blood coagulation reactions--vitamin K deficiency, hepatocellular disease, antibodies to clotting factors, and disseminated intravascular coagulation--but limit my comments to the mechanisms that trigger the formation of antibodies to clotting factors and how these antibodies can deplete the blood of clotting factor activities. Finally, heparin is able to potentiate tissue factor pathway inhibitor function, which is a possible reason why the use of heparin but not warfarin can prevent the numerous thrombotic episodes of the Trousseau's syndrome.
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PMID:Blood coagulation and its alterations in hemorrhagic and thrombotic disorders. 843 80

To determine the relationship between vitamin K dependent coagulation factors and natural anticoagulants, namely protein C and protein S, in various degrees of vitamin K deficiency, plasma values for clotting activity, protein induced by vitamin K absence (PIVKA-II), protein C antigen, gamma-carboxy protein C antigen, and protein S antigen including total and free fractions and activity of protein C were measured in 66 full term and healthy breast fed neonates who did not receive vitamin K supplement at birth. The 66 neonates were divided into a control group (17 cases) and a low group (49 cases) according to their values for clotting activity--that is, > or = 20% or < 20% during the first six days of life--and vitamin K was immediately given when the neonates showed values < 20%. In the low group clotting activity gamma-carboxy protein C, free protein S, and protein C activity was significantly decreased to a minimum on day 2 or 3, and increased in parallel after vitamin K administration. Furthermore, they were positively correlated with one another and inversely cor-correlated with the PIVKA-II concentrations. These findings suggest that simultaneous gamma-carboxylation of coagulation factors and proteins C and S acts to maintain both coagulation and anticoagulation activities in parallel at various concentrations of vitamin K. The breast milk intake in the group with low values of clotting activity was significantly lower than that in the control group during the first three days of life.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship between vitamin K dependent coagulation factors and anticoagulants (protein C and protein S) in neonatal vitamin K deficiency. 846 66

A subclinical vitamin K deficiency was induced in 32 healthy subjects (four groups of eight males and females) aged 20-40 and 60-80 yr residing in the Metabolic Research Unit of the Human Nutrition Research Center on Aging at Tufts University. Volunteers were initially fed (4 d) a baseline-period diet containing the recommended daily allowance for vitamin K which is equivalent to 80 micrograms/d of phylloquinone (vitamin K1). During the baseline period various parameters of vitamin K nutritional status were monitored. The baseline period was followed by a 13-d depletion period during which the subjects were fed a very low vitamin K1 diet (approximately 10 micrograms/d). After depletion, the subjects entered a 16-d repletion period (four stages lasting 4 d each) during which time they were repleted with 5, 15, 25, and 45 micrograms of vitamin K1 per day. Vitamin K1 depletion dramatically and significantly decreased plasma vitamin K1 levels (P < 0.0001) in both elderly and young groups to values 13-18% of day 1 (elderly 0.22 nM, young 0.14 nM). Repleting the subjects with up to 45 micrograms of vitamin K1 per day failed, in the case of the young subjects, to bring plasma vitamin K1 levels back into the normal range. Dietary vitamin K1 restriction induced different responses in the urinary excretion of gamma-carboxyglutamic acid between the young and the elderly subjects with values decreasing significantly (P < 0.03) in the young while remaining unchanged in the elderly. The vitamin K1 depletion period had no significant effect on either prothrombin and activated partial thromboplastin times, or Factor VII and protein C (as determined by antigenic and functional assays). By using a monoclonal antibody, decarboxy prothrombin was found to increase slightly but significantly in both groups (P < 0.05) as a consequence of the low vitamin K1 diet. This study clearly shows that a diet low in vitamin K1 can result in a functional subclinical deficiency of vitamin K (decreased urinary gamma-carboxyglutamic acid excretion) without affecting blood coagulation.
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PMID:Dietary induced subclinical vitamin K deficiency in normal human subjects. 847 81

Vitamin K is a cofactor for the synthesis of blood coagulation Factors II, VII, IX and X, and inhibitors such as Protein C and S and bone matrix protein. Its active form is a coenzyme in the glutamic acid carboxylation. Vitamin K-dependent factors form enzymatic complexes with calcium and membrane phospholipids. The insufficiency of gamma glutamic carboxylation impairs the hemostatic function. Hereditary deficiencies, antibiotics and oral anticoagulants, decrease the capacity of complex formation giving way to hemorrhage or thrombosis, or bone mass disturbances which are easily treated with administration of Vitamin K. The main causes of Vitamin K deficiency are lack of hepatic storage in newborns, liver insufficiency, malabsorption, dietetic deficiency, therapy with the antibiotics and coumarin administration. For the study of Vitamin K there are methods to measure the Vit K dependent proteins and as well methods to measure specifically the quinonas.
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PMID:[Vitamin K: biochemistry, function, and deficiency. Review]. 978 May 55

Calciphylaxis is a rare disorder of small-vessel calcification and cutaneous infarction associated with chronic renal failure. Rare cases of calciphylaxis not associated with chronic renal failure have been reported with breast cancer, hyperparathyroidism, and alcoholic cirrhosis. To our knowledge, we report the first case of calciphylaxis without chronic renal failure associated with cholangiocarcinoma and the first attempt to treat calciphylaxis with vitamin K. A 56-year-old woman presented with necrotic leg ulceration. She was treated initially with low-molecular-weight heparin, with no effect. A coagulation work-up showed vitamin K deficiency. During vitamin K therapy, the patient had fulminant progression of the calciphylaxis. She died, and an autopsy showed metastatic cholangiocarcinoma. Thrombosis and protein C deficiency have been implicated in the pathophysiology of calciphylaxis. Functional protein C deficiency may be one of several factors contributing to the development of calciphylaxis. Vitamin K therapy was ineffective in our patient and may have been detrimental.
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PMID:Calciphylaxis associated with cholangiocarcinoma treated with low-molecular-weight heparin and vitamin K. 1144 9

Acquired factor VII (FVII) deficiency in the absence of vitamin K deficiency, oral anticoagulant therapy, synthetic liver dysfunction, or DIC is rare, with only a handful of cases thus far reported. In the period from 1990 to 1996 we identified eight patients with acquired FVII deficiency, all of whom presented with prolongation of the prothrombin time (PT) in the first 2 weeks following stem cell transplantation (SCT). The mean plasma FVII clotting activity (FVII:c) was 22% (range 8-35%) with an approximately equivalent reduction in FVII antigen (FVII:Ag) level. Mean plasma levels of fibrinogen and factors II, V, IX, and X were normal. Protein C activity was significantly depressed in only one of the three patients in whom it was measured. Several patients experienced bleeding complications, and hemorrhage directly accounted for death in two cases. Veno-occlusive disease of the liver developed in three patients. We conclude that FVII deficiency should be considered in the differential diagnosis of prolonged PT in patients who have recently undergone SCT. The mechanism of this acquired deficiency state remains to be defined.
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PMID:Acquired factor VII deficiency in hematopoietic stem cell transplant recipients. 1191 30

Our objective was to characterize the etiologic factors and outcome for stroke in children. We retrospectively reviewed the charts of patients between the ages of 40 days and 94 months (36.5 +/- 23.7 months) with stroke seen at Istanbul Medical Faculty, Department of Pediatrics between January 1995 and December 2003. We found 79 cases of stroke: 57 ischemic and 22 hemorrhagic strokes. Seventeen children had vitamin K deficiency dependent hemorrhage. In 14 children stroke occurred as a complication of cardiac disease, 7 had moyamoya disease, 3 had protein C deficiency, 2 had thalassemia, 2 had hyperhomocysteinemia (methylene tetrahydrofolate reductase gene mutation), 2 were heterozygote for factor V Leiden, 3 had Down's syndrome, 1 was diagnosed with antiphospholipid syndrome, 1 had glycogen storage disease, and in 28 children no underlying cause could be found. Multiple risk factors were found in 4 children. The outcome in all 79 stroke patients was as follows: asymptomatic 60%; symptomatic epilepsy or persistent neurologic deficit 37%; death 3%; and recurrent stroke 5%. Thus, an underlying cause for stroke was identified in 65% of the children in the study group; 40% of the children either died or suffered motor and/or cognitive sequelae.
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PMID:Stroke in childhood: experience in Istanbul, Turkey. 1663 11

Hematologic disorders are frequently encountered in the intensive care unit. Thrombocytopenia, often defined as a platelet count below 100,000/microL, is common in critically ill patients and may be associated with adverse outcomes. A systematic evaluation of clinical and laboratory findings is necessary to ascertain the cause of the thrombocytopenia and to determine the correct therapy. Recognition of heparin-induced thrombocytopenia (HIT) is particularly important, given the risk of thrombosis associated with this condition. Prompt cessation of all heparin products is required, and anticoagulation with a direct thrombin inhibitor is recommended if HIT is strongly suspected. Coagulopathies are also common in the critically ill, and are often due to vitamin K deficiency or disseminated intravascular coagulation (DIC). A careful history and interpretation of clotting studies are useful in defining the coagulation defect. Advances in understanding the pathogenesis of DIC have generated new treatment approaches, such as the use of recombinant activated protein C. Recombinant factor VIIa (rFVIIa) is a novel drug approved for use in patients with congenital hemophilia and inhibitors. Although its use as a hemostatic agent is currently being evaluated in several off-label scenarios, including trauma, intracerebral hemorrhage, and liver disease, there are limited data to guide therapy in these conditions.
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PMID:Hematologic disorders in critically ill patients. 1679 61

Skin necrosis caused by heparins is a rare complication. We report a case of a 71-yr-old white woman who developed painful diffuse skin lesions, most probably related to enoxaparin treatment. Other causes of skin necrosis, including heparin induced thrombocytopenia, disseminated intravascular coagulation, protein C/protein S deficiencies, anti-phospholipid antibodies, and vitamin K deficiency were less likely in this case. The concomitant combined thrombophilia possibly aggravated the patient's clinical presentation.
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PMID:A fatal case of enoxaparin induced skin necrosis and thrombophilia. 1685 10


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