Coagulation abnormalities in liver disease.

Abstract

Hemostasis is intimately related to liver function, because most coagulation factors are synthesized by liver parenchymal cells and the liver's reticuloendothelial system serves an important role in the clearance of activation products. The extent of coagulation abnormalities depends upon the degree of disturbed liver function. Acute or chronic hepatocellular diseases may display decreases in the vitamin K-dependent factors (prothrombin; factors VII, IX, and X; proteins C and S), whereas other parameters remain normal. Patients with hepatic failure may present with the entire spectrum of factor deficiencies and may even develop disseminated intravascular coagulation (DIC). Patients with liver cirrhosis have a wide spectrum of abnormalities. Except for factor VIII:C and von Willebrand factor, all procoagulant and inhibitory factors are decreased, which is a reflection of impaired protein synthesis. Abnormal fibrinogen and prothrombin molecules can be identified. Platelets are quantitatively and qualitatively altered, and most patients develop DIC. Vitamin K deficiency leads to the production of abnormal vitamin K-dependent factors. The factors lack gamma-carboxy glutamic acid residues in the NH2-terminal part of their molecules. Surgery associated with the liver leads to major hemostasis alterations. The LeVeen shunt is invariably related to DIC. Bleeding with partial liver resection is mostly mechanically induced, but chronic DIC may be present. Orthotoptic liver transplantation is associated with severe hemorrhages. These are partly due to the pre-existing hemostasis defects and partly due to DIC with a marked fibrinolytic response. This is especially noted during the anhepatic phase and when the donor liver is perfused by the recipient's blood. Postoperative recovery is quick, provided the graft is not rejected. Postoperatively, there may be an initial hypercoagulable state, which could be related to the thrombosis occasionally encountered.