A hepatologist's perspective on the management of coagulation disorders before liver transplantation.

Abstract

I ntact liver function is essential to maintain normal hemostatic mechanisms. Many of the proteins required for proper coagulation are synthesized by hepatocytes, including prothrombin (II); fibrinogen (I); factors V, VII, VIII, IX, X, XI, XII, and XIII; antithrombin III; plasminogen; a2 antiplasmin; protein C; and protein S.1-5 Traditionally, liver-derived coagulation factors have been divided into those whose final function is either dependent or independent of vitamin K. The vitamin K– dependent factors are II, VII, IX, X, protein C, and protein S (Table 1). Thus the liver is responsible for production of both procoagulant and anticoagulant proteins integral to normal hemostasis. The effect of liver disease on coagulation is complex; not only is production of coagulation factors diminished, but portal hypertension and hypersplenism cause entrapment of platelets in the spleen and thrombocytopenia. Because liver disease alters all pathways in the body’s protective coagulation and anticoagulation cascades, patients with advanced disease can experience severe bleeding or even thrombotic complications. Death from liver disease commonly results from severe gastrointestinal bleeding or bleeding into vital organs or structures. Management of coagulopathy is complicated by other features of chronic liver disease, particularly portal hypertension and malnutrition.5 Although correction of coagulopathy with fresh-frozen plasma and vitamin K is central to treatment of cirrhotic patients with variceal bleeding, it is essential also to treat the underlying portal hypertension. The latter may be effectively controlled by pharmacotherapy, decompressive portal-systemic shunt surgery, or transjugular intrahepatic portosystemic shunting (TIPS). Although it is often ignored, provision of appropriate nutritional support (enteral feedings or total parenteral nutrition [TPN]) may also improve the general clinical state of the patient and aid in management of bleeding risk. Liver transplantation cures the coagulopathy of liver disease and is the final therapeutic maneuver for eligible patients. The goal of this article is to briefly introduce the reader to the various concepts noted above. I highlight the most common coagulation abnormalities encountered in the treatment of patients with end-stage disease and provide treatment guidelines. Rarer coagulation problems are described to familiarize the reader with the general and specific abnormalities that may be encountered.