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

Stephen H. Caldwell, Maureane Hoffman, Ton Lisman, B. Gail Macik, Patrick G. Northup, K. Rajender Reddy, Armando Tripodi, Arun J. Sanyal, Nathan Bass, Andres T. Blei, Michael Fallon, Don Gabriel, Pere Gines, Peter Grant, Kris Kowdley, Samuel Lee, Santiago Munoz, Ian Wanless, Abdullah M. Al-Osaimi, Carl I. BergRasheed Balogun, Thomas Bleck, David L. Bogdonoff, Andrew Martoff, Paul Mintz, Timothy L. Pruett

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1039-1046
Number of pages8
JournalHepatology
Volume44
Issue number4
DOIs
Publication statusPublished - Oct 2006

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ASJC Scopus subject areas

  • Hepatology

Cite this

Caldwell, S. H., Hoffman, M., Lisman, T., Macik, B. G., Northup, P. G., Reddy, K. R., Tripodi, A., Sanyal, A. J., Bass, N., Blei, A. T., Fallon, M., Gabriel, D., Gines, P., Grant, P., Kowdley, K., Lee, S., Munoz, S., Wanless, I., Al-Osaimi, A. M., ... Pruett, T. L. (2006). Coagulation disorders and hemostasis in liver disease: Pathophysiology and critical assessment of current management. Hepatology, 44(4), 1039-1046. https://doi.org/10.1002/hep.21303