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Semin Thromb Hemost 2021; 47(07): 759-774
DOI: 10.1055/s-0041-1727116
Review Article

Thrombin: A Pivotal Player in Hemostasis and Beyond

Julie Brogaard Larsen
1   Department of Clinical Biochemistry, Thrombosis and Hemostasis Research Unit, Aarhus University Hospital, Aarhus, Denmark
,
Anne-Mette Hvas
1   Department of Clinical Biochemistry, Thrombosis and Hemostasis Research Unit, Aarhus University Hospital, Aarhus, Denmark
2   Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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Abstract

The serine protease thrombin, a naturally derived enzyme, plays a key role in hemostasis by converting fibrinogen to fibrin and activating coagulation factor XIII whereby the fibrin clot is stabilized. Furthermore, thrombin activates platelets through protease-activated receptors on the platelet surface. Conversely, thrombin also exerts anticoagulant effects, enhancing the protein C activity while complexed with thrombomodulin. During recent years, it has become evident that thrombin has significant effects beyond hemostasis, as it contributes also to modulation of the endothelium, promotes inflammation and angiogenesis, and plays a role in tumor progression. Yet, due to the very short half-life and almost immediate inhibition in fluid phase by antithrombin, thrombin itself remains elusive, and only indirect measurement of thrombin generation is possible. This review provides a description of structure and mechanisms of action of thrombin both in physiological and pathological processes. Furthermore, it summarizes laboratory tests that measure in vivo or ex vivo thrombin generation, and presents knowledge on the value of these biomarkers in bleeding disorders, cardiopulmonary bypass surgery, and thromboembolic risk assessment in different patient populations. Finally, this review outlines further perspectives on using thrombin generation biomarkers for research purposes and in clinical practice.

Keywords

thrombin - prothrombin - blood coagulation - thrombosis - thrombin generation - prothrombin fragment 1 + 2 - thrombin–antithrombin complex


Publication History

Article published online:
21 June 2021

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