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Adv Clin Chem. 2020;94:31-84. doi: 10.1016/bs.acc.2019.07.008. Epub 2019 Oct 18.

Clotting factors: Clinical biochemistry and their roles as plasma enzymes.

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University of Florida, Department of Pathology, Immunology & Laboratory Medicine, Gainesville, FL, United States.
Laboratory Services, Kaiser Permanente, Renton, WA, United States.
UF Health Shands Hospital, Gainesville, FL, United States.
University of Florida, Department of Pathology, Immunology & Laboratory Medicine, Gainesville, FL, United States. Electronic address:


The purpose of this review is to describe structure and function of the multiple proteins of the coagulation system and their subcomponent domains. Coagulation is the process by which flowing liquid blood plasma is converted to a soft, viscous gel entrapping the cellular components of blood including red cells and platelets and thereby preventing extravasation of blood. This process is triggered by the minimal proteolysis of plasma fibrinogen. This transforms the latter to sticky fibrin monomers which polymerize into a network. The proteolysis of fibrinogen is a function of the trypsin-like enzyme termed thrombin. Thrombin in turn is activated by a cascade of trypsin-like enzymes that we term coagulation factors. In this review we examine the mechanics of the coagulation cascade with a view to the structure-function relationships of the proteins. We also note that two of the factors have no trypsin like protease domain but are essential cofactors or catalysts for the proteases. This review does not discuss the major role of platelets except to highlight their membrane function with respect to the factors. Coagulation testing is a major part of routine diagnostic clinical pathology. Testing is performed on specimens from individuals either with bleeding or with thrombotic disorders and those on anticoagulant medications. We examine the basic in-vitro laboratory coagulation tests and review the literature comparing the in vitro and in vivo processes. In vitro clinical testing typically utilizes plasma specimens and non-physiological or supraphysiological activators. Because the review focuses on coagulation factor structure, a brief overview of the evolutionary origins of the coagulation system is included.


Coagulation factors; Enzyme catalysis; Extrinsic and intrinsic pathway; Fibrinogen; Prothrombin; Serine protease; Tissue factor

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