Cardiovascular Medicine

pp 2423-2438

Hypercoagulable State

  • Andrew I. SchaferAffiliated withDepartment of Medicine, University of Pennsylvania

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  • The term hypercoagulable states is used interchangeably with thrombophilia or prethrombotic state to refer to hereditary or acquired conditions that predispose individuals to thrombosis.

  • The coagulation system, also known as the coagulation cascade, is a highly coordinated and tightly linked series of enzymatic reactions, involving the sequential conversion of plasma clotting factors that circulate in their inactive zymogen forms to enzymatically active serine proteases, culminating in the formation of fibrin.

  • The coagulation system is normally kept in check by several physiological anticoagulant (antithrombotic) mechanisms. These include antithrombin III, the protein C/protein S/thrombomodulin system, tissue factor pathway inhibitor, the protein Z/protein Z-dependent protease inhibitor system, and the fibrinolytic system.

  • Primary hypercoagulable states are mostly inherited thrombophilias caused by (1) quantitative deficiencies or qualitative defects of the physiologic anticoagulants, or (2) increased levels or function of the coagulation factors.

  • Secondary hypercoagulable states encompass a variety of diseases and conditions, most of which are acquired, which predispose individuals to thrombosis by complex and multifactorial mechanisms.

  • In gene-gene interactions, the inheritance of more than one thrombophilic defect leads to an increased lifelong risk of thrombosis.

  • In gene-environment interactions, many thrombotic complications in individuals with inherited (primary) hypercoagulable states are precipitated by acquired, acute thrombogenic insults, pointing to complex interactions between genetic and environmental factors in the pathogenesis of clinical thrombotic events.

  • The hypercoagulable workup is a laboratory evaluation of individuals with suspected hypercoagulable states. It is guided by the history, physical examination, and implications for management decisions.