Coagulation disorders and hemostasis in liver disease: Pathophysiology and critical assessment of current management

Authors


  • Potential conflict of interest: Dr. Caldwell advises, is on the Speakers' Bureau for, and received grants from Novo Nordisk. Dr. Hoffman is a consultant and is on the Speakers' Bureau for Novo Nordisk. Dr. Lisman received grants from Novo Nordisk.

  • Members of Coagulation in Liver Disease Group: Nathan Bass, M.D., of the University of California San Francisco; Andres T. Blei, M.D., of Northwestern University; Michael Fallon, M.D., of the University of Alabama; Don Gabriel of the University of North Carolina Chapel Hill; Pere Gines, M.D., of the University of Barcelona, Spain; Peter Grant, M.D., of the University of Leeds, UK; Kris Kowdley, M.D., of the University of Washington; Samuel Lee, M.D., of the University of Calgary, Canada; Santiago Munoz, M.D., of Albert Einstein Medical Center, Ian Wanless, M.D., of the University of Toronto, Canada; and Abdullah M. Al-Osaimi M.D., Carl L Berg, M.D., Rasheed Balogun, M.D., Thomas Bleck, M.D., David L. Bogdonoff, M.D., Andrew Martoff, D.D.S., Paul Mintz, M.D., Timothy L. Pruett, M.D., of the University of Virginia.

Abstract

Normal coagulation has classically been conceptualized as a Y-shaped pathway, with distinct “intrinsic” and “extrinsic” components initiated by factor XII or factor VIIa/tissue factor, respectively, and converging in a “common” pathway at the level of the FXa/FVa (prothrombinase) complex. Until recently, the lack of an established alternative concept of hemostasis has meant that most physicians view the “cascade” as a model of physiology. This view has been reinforced by the fact that screening coagulation tests (APTT, prothrombin time – INR) are often used as though they are generally predictive of clinical bleeding. The shortcomings of this older model of normal coagulation are nowhere more apparent than in its clinical application to the complex coagulation disorders of acute and chronic liver disease. In this condition, the clotting cascade is heavily influenced by numerous currents and counter-currents resulting in a mixture of pro- and anticoagulant forces that are themselves further subject to change with altered physiological stress such as super-imposed infection or renal failure. This report represents a summary of a recent multidisciplinary symposium held in Charlottesville, VA. We present an overview of the coagulation system in liver disease with emphasis on the limitations of the current clinical paradigm and the need for a critical re-evaluation of the current tenets governing clinical practice. With the realization that there is often limited or conflicting data, we have attempted to represent diverse opinion and experience from the perspectives of both hepatology and hematology beginning with a brief update on the physiology of normal coagulation. (HEPATOLOGY 2006;44:1039–1046.)

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