Role of the blood coagulation cascade in hepatic fibrosis.

Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901227 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1547 (Electronic) Linking ISSN: 01931857 NLM ISO Abbreviation: Am J Physiol Gastrointest Liver Physiol Subsets: MEDLINE

Original Publication: Bethesda, MD : American Physiological Society

Blood Coagulation/*physiology ; Blood Coagulation Factors/*metabolism ; Liver Cirrhosis/*blood; Animals ; Humans

Liver is the primary source of numerous proteins that are critical for normal function of the blood coagulation cascade. Because of this, diseases of the liver, particularly when affiliated with severe complications like cirrhosis, are associated with abnormalities of blood clotting. Although conventional interpretation has inferred cirrhosis as a disorder of uniform bleeding risk, it is now increasingly appreciated as a disease wherein the coagulation cascade is precariously rebalanced. Moreover, prothrombotic risk factors are also associated with a more rapid progression of fibrosis in humans, suggesting that coagulation proteases participate in disease pathogenesis. Indeed, strong evidence drawn from experimental animal studies indicates that components of the coagulation cascade, particularly coagulation factor Xa and thrombin, drive profibrogenic events, leading to hepatic fibrosis. Here, we concisely review the evidence supporting a pathologic role for coagulation in the development of liver fibrosis and the potential mechanisms involved. Further, we highlight how studies in experimental animals may shed light on emerging clinical evidence, suggesting that beneficial effects of anticoagulation could extend beyond preventing thrombotic complications to include reducing pathologies like fibrosis.

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R01 DK105099 United States DK NIDDK NIH HHS; R01 ES017537 United States ES NIEHS NIH HHS

Keywords: anticoagulants; coagulation; fibrosis; liver

0 (Blood Coagulation Factors)

Date Created: 20180504 Date Completed: 20190702 Latest Revision: 20240331

20240331

PMC6139645

10.1152/ajpgi.00402.2017

29723040