Management of Coagulopathy in Cirrhotic Patients Undergoing Invasive Procedures: a Prospective Trial Comparing Standard Management to Thromboelastography Protocol Based Management

Background

Recently there has been a change of concept regarding the hemostatic profile of patients with liver disease from "auto-anti-coagulation" to "rebalanced hemostasis". The liver synthesizes most of the factors and inhibitors of the coagulation system as well as thrombopoietin. Thus, liver disease influences the hemostatic profile both through an effect on factor/inhibitor levels and through an effect on platelet number and function. The "rebalanced hemostasis" of liver disease results from decreased levels of most proteins involved in coagulation; promotors and inhibitors. Two proteins which are elevated in this state are factor VIII and von Willebrand factor. Elevated levels of the latter compensate to some extent for the thrombocytopenia and platelet function defects. This "rebalanced" state is not well reflected by conventional coagulation tests (CCT), which are insensitive to the anticoagulant component of hemostasis. In fact, it has been shown that thrombin generation in cirrhotic patients is normal. Considering this conceptual change together with the well-known adverse effects of blood product administration the investigators seek to re-evaluate the clinical management of cirrhotic patients undergoing invasive procedures.

Thromboelastography (TEG) provides a graphic representation of clot formation and lysis. Compared with CCTs, TEG better reflects the interaction of plasma, blood cells and PLTs and better resembles the in-vivo state. Viscoelastic tests have been used for many years for coagulation monitoring and hemostatic therapy guidance during liver transplantation. Their use in hospitalized patients with liver disease has been much more limited.

Different guidelines address the issue of coagulation test abnormalities in cirrhotic patients prior to various specific invasive procedures. According to the European Association for the Study of the Liver clinical practice guidelines, in cirrhosis, hemorrhagic complications after large volume paracentesis (LVP) are infrequent and there is no data to support pre-procedural use of fresh frozen plasma (FFP) or PLTs. The authors do note that often these products are given in case of severe coagulopathy and/or thrombocytopenia, and that caution should still be exercised in patients with severe coagulopathy, and LVP avoided in the presence of disseminated intravascular coagulation. The American Association for the Study of Liver Diseases practice guidelines state that because bleeding is uncommon, routine administration of FFP or PLTs prior to paracentesis is not recommended.

Very few randomized, double-blind controlled clinical trials regarding the management of coagulation issues in patients with liver disease exist. Some guidelines note that INR should not be used alone to assess bleeding risk, that a PLT count greater than 50-60x10^9/L should be achieved prior to high-risk procedures, and that TEG may be helpful in targeting transfusion practice. Pertaining to esophageal varices, few data support the notion that coagulopathy is directly related to bleeding risk, and despite the existence of various specific guidelines on management of esophageal varices, specific recommendations on coagulation parameters for prophylactic esophageal variceal band ligation (EVBL) are missing. When prophylactic EVBL is deemed unsafe due to a coagulation disorder, they recommend avoiding it. Although it is uncertain what the optimal platelet counts should be in this situation, they recommend levels exceeding 56x10^9/L and possibly a fibrinogen level above 100-150 mg/dL. They note that FFP transfusion is problematic because of the large volume needed to "correct" the INR.