Coagulopathy Management in Liver Transplantation

Abstract

When end stage liver disease occurs, liver transplantation is the only effective treatment available. In the past, liver transplantation was frequently accompanied by considerable bleeding complications and massive transfusion requirements, while only in recent years advances in operative management and a better understanding of the pathophysiology of coagulation have determined a better outcome for this major surgery. In addition, accumulating evidence shows that the overall haemostatic function in patients with cirrhosis facing liver transplantation may not be shifted towards a bleeding diathesis as traditionally believed, but that both bleeding episodes and thrombotic events may take place as major peri- and post-operative complications in patients undergoing liver surgery. Liver transplantation is frequently complicated by hemostatic defectsassociated with end-stage liver disease, surgical bleeding, and the graftedorgan recovering from ischemia and reperfusion injury. Managementof hemostatic defects in patients undergoing liver transplantation, therefore, requires a thorough understanding of pathophysiology ofcoagulation, clinically relevant assessment of coagulation, and theselection of rational treatment modes.

The liver plays a central role in the clotting process, and acute and chronic liver diseases are invariably associated with coagulation disorders due to multiple causes: decreased synthesis of clotting and inhibitor factors, decreased clearance of activated factors, quantitative and qualitative platelet defects, hyperfibrinolysis, and accelerated intravascular coagulation. The bleeding tendency accounts for increased risk of morbidity and mortality in patients with liver disease undergoing diagnostic or therapeutic invasive procedures. Risk of bleeding and transfusion in liver transplantation is determined by age, severity of liver disease, as well as hemoglobin and plasma fibrinogen values. During the hepatectomy and the anhepatic phase, the coagulopathy is related to a decrease in clotting factors caused by surgical bleeding, facilitated by the increased portal hypertension and esophageal-gastricvenous distension. Corrections of hematologic disturbances by administration of large volumes of crystalloid, colloid, or blood products may worsen the coagulopathy. Also, impaired clearance of fibrinolytic enzymes released from damaged cells can lead to primary fibrinolysis. At time of graft reperfusion further deterioration may occur as characterized by global reduction among all coagulation factors, decreased plasminogen activator inhibitor factors, and simultaneous generation of tissue plasminogen activator. In situations with inherent risk of bleeding, hypofibrinogenemia must be corrected. Concern about unwanted events is a major limitation of preventive therapy. There is some evidence for the efficacy of antifibrinolytic drugs to reduce red blood cell requirements. A guide for antifibrinolytic therapy are clot firmness in trhomboelastometry or alternatively, diffuse bleeding associated to a fibrinogen value less than 1 g/L. Because thrombin generation is limited in severe thrombocytopenia, platelet administration is recommended when active bleeding coexists with a platelet count below 50, 000/mm3. When the administration of hemoderivates and antifibrinolytic drugs does not correct severe bleeding, consumption coagulopathy and secondary fibrinolysis should be suspected. Treatment of affected patients should be based upon correcting the underlying cause, mostly related to tissue hypoxia due to critical hypoperfusion.