The liver is the major site of synthesis of almost all coagulation factors, except for Factor VIII and vWF. Liver failure is associated with decreased coagulation factors, decreased or dysfunctional platelets, dysfibrinogenemia and fibrinolysis. Patients with severe liver disease have lower levels of those coagulation factors synthesized by the liver. Inadequate vitamin K absorption may occur as a result of decreased bile acid secretion into the intestine, leading to a reduction in coagulation factors II, VII, IX and X. Abnormal forms of fibrinogen may be produced causing dysfibrinogenemia. Inhibitors of fibrinolysis, such as alpha-2 antiplasmin, are also decreased. Tissue plasminogen activator (TPA), which is produced by the endothelium and metabolized by the healthy liver, is elevated. Decreased alpha-2 antiplasmin and increased TPA cause fibrinolysis and hypofibrinogenemia. Platelet count may be decreased due to inadequate marrow production, sequestration associated with hypersplenism or consumption by low grade disseminated intravascular coagulation (DIC).Some patients may undergo liver transplantation. During reperfusion of the grafted liver, there is a further deterioration in coagulation due to endothelial cell injury in the donor organ, leading to further release of plasminogen activators. Additionally, heparin-like activity can be detected in the blood of many patients in the post-reperfusion phase of liver transplantation, even when there is no known source of exogenous heparin. Reperfusion coagulopathy resolves as graft function improves.Post liver transplantation, the imbalance shifts towards hypercoagulability, especially in children, due to exposure of tissue factor (TF) resulting from traumatic injury to a large capillary bed, venous stasis during clamping of the portal vein and inferior vena cava, ischemic insult to the intestines, activator release from the grafted liver, and blood transfusion.All of these coagulation factor abnormalities can be monitored in a clinical laboratory with a thromboelastograph (TEG).


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