Coagulation and liver transplantation: Current concepts

Abstract

C omplications associated with bleeding and coagulopathy during liver transplantation have become manageable in recent years. Neuhaus pointed out that a new understanding of coagulation disorders has allowed more specific therapy instead of blind substitution and replacement policy. 1 He emphasized the important role of pharmacological therapy against fibrinolysis and the contribution of the prevention of coagulopathy to other postoperative complications. However, refined surgical technique might have played a more significant role in reducing blood loss, and understanding of pathophysiology, monitoring, and management of coagulation is far from its desirable level. Coagulation in Cirrhosis and During Liver TransplantationCirrhosis-induced coagulopathy has been described for the past several decades. Briefly, the vascular phase is impaired as cirrhosis is complicated by peripheral vasodilation, reduced elasticity of vessels, and decreased interaction between the vessel walls and platelets. The platelet phase is severely affected by thrombocytopenia and platelet dysfunction. The coagulation cascade is affected by low levels of procoagulants and inhibitors produced by the liver, including coagulation factors (I, II, V, VII, VIII, IX, X, XI, XII, XIII, Fletcher, Fitzgerald, prekallikrein, plasminogen, and highmolecular-weight kininogen), inhibitors (AT-III and ␣ 1 -antitrypsin), and regulatory proteins (C1 inhibitor and ␣ 2 -macroglobulin). An excessive sialic acid content of fibrinogen results in dysfibrinogenemia, and the level of factor VIII is increased because of increased levels of von Willebrand' s factor (vWF) antigen and its activity. Fibrin polymerization is impaired by the low level of factor XIII and dysfibrinogenemia. 2 As a result, a hypocoagulable state is the common denominator, although the imbalance between coagulation and its inhibition and fibrinolysis and its inhibition result in all forms of coagulopathy.Intraoperative changes in coagulation were studied extensively during early clinical experience, and only limited information has been added in the past two decades. 3 During the preanhepatic and anhepatic stages, the levels of all coagulation factors and platelet count decrease as preexisting coagulopathy is compounded by surgical bleeding. Furthermore, fibrinolysis in patients with severe hepatocellular disease or in those requiring massive transfusion and activation of coagulation reduces procoagulant level even with an infusion of blood products rich in coagulation factors. Hypothermia and ionized hypocalcemia also impair coagulation.A severe coagulopathy, a component of the postreperfusion syndrome, occurs on reperfusion of the grafted liver; more specifically, a decrease in coagulation factor levels, a sudden increase in tPA, thrombocytopenia, fibrinolysis, and a moderate increase in FDP and TAT levels are seen. 4 The cause of the postreperfusion coagulopathy is multifactorial. The release of endogenous heparin from the donor liver results in moderate to severe heparin effect in approxima...

The prevalence of a heparin-like effect shown on the thromboelastograph in patients undergoing liver transplantation

“…The use of protamine in cases in which HLE is present is controversial. Kang,2 Pivalizza et al,18 and Mallett et al6 have all used protamine in vitro to demonstrate the reversal of HLE. One case report describes the use of protamine to neutralize the heparin effect in an attempt to decrease perioperative blood loss15; in vivo, however, there is little evidence that it affects intraoperative blood loss.…”

“…The Thromboelastograph (TEG) was first used during orthotopic liver transplantation by Kang et al1 in the 1980s as a bedside monitor of coagulation, and it is a standard guide to transfusion of various blood components in many transplant centers 2. Typical changes seen in TEG on reperfusion of the graft liver include a lengthening of the reaction time (R time) and coagulation time (K time), a diminished maximum amplitude, and an increase in fibrinolysis 2. This phenomenon is partly explained by the heparin‐like effect (HLE) because even a small amount of heparin in the circulation prolongs R time and, in some cases, K time 3, 4.…”

Coagulation profiles and intraoperative substitution requirements during elective piggyback liver transplantation with prophylactic antifibrinolytic therapy

“…Disseminated intravascular coagulation (DIC) and fibrinolysis have been described during the anhepatic and reperfusion phase in standard OLT [12,19,231. Consumption of extrinsic coagulation factors (11, V, VII, and X) is considered to be responsible for the pathological PT activity present in 90% of patients with DIC [8].…”

“…The hazard of hemostatic imbalances is a well known feature during orthotopic liver transplantation (OLT) in humans, frequently necessitating the intraoperative substitution of rather large quantities of coagulation factors and blood products [3,12,17,19,231. In this context, different factors contribute to the abnormalities of the coagulation system, which may sustain intraoperative bleeding.…”

“…As a result, abnormal preoperative levels of procoagulants and coagulation factors (I, 11, V, VII, IX-XIII) [2,11,14,18,19,221, inhibitors (AT-I11 and alpha-2-antiplasmin) [l, 26, 271 and regulatory proteins (C1 inhibitor and prekallikrein) [7, 271 are frequently observed. In addition, portal hypertension, peripheral vasodilatation, and thrombocytopenia are frequently found in states of liver cirrhosis [12,231. Characteristic features of hemostatic disorders during standard OLT are disseminated intravascular coagulation (DIC) and fibrinolysis as well as abnormal platelet counts and function [l, 10, 12, 18, 19, 231.…”