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The Biologic Impact of Hereditary Defects that Cause Thrombosis

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Recombinant Technology in Hemostasis and Thrombosis

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Abstract

Considerable effort has been devoted to investigating the natural anticoagulant mechanisms that regulate the hemostatic mechanism. Two of these are the heparan sulfate-antithrombin III and protein C-thrombomodulin-protein S mechanisms that inactivate the serine proteases and activated cofactors of the coagulation cascade, respectively.1, 2 Antithrombin III neutralizes the activity of thrombin as well as factors Xa, IXa, XIa, and XIIa. Heparan sulfate associated with endothelial cells of the vessel wall accelerates the inactivation of these enzymes. To perform its anticoagulant function, protein C, a vitamin-K dependent glycoprotein, is converted to activated protein C when thrombin binds to thrombomodulin on vascular endothelial cell membranes. Activated protein C inhibits the platelet-dependent conversion of prothrombin to thrombin via factor Xa by destroying factor Villa and platelet-bound factor Va. Protein S enhances the binding of activated protein C to phospholipid-containing membranes and accelerates the proteolytic inactivation of factor Villa and factor Va. The association of severe thrombotic disease in persons with hereditary deficiencies of antithrombin III, protein C, or protein S demonstrates the physiologic importance of these natural anticoagulants in vivo. This chapter describes the clinical features, laboratory evaluation, and management of patients with these familial disorders.

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Authors and Affiliations

  1. Brockton-West Roxbury Veterans Administration Medical Center, Harvard Medical School, 1400 VFW Parkway, West Roxbury, MA, 02132, USA

    Kenneth A. Bauer

  2. Beth Israel Hospital, 330 Brookline Avenue, Boston, MA, 02215, USA

    Kenneth A. Bauer

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  1. Kenneth A. Bauer
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  1. Jerome H. Holland Laboratory, American Red Cross Blood Services, Rockville, Maryland, USA

    Leon W. Hoyer  & William N. Drohan  & 

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Bauer, K.A. (1991). The Biologic Impact of Hereditary Defects that Cause Thrombosis. In: Hoyer, L.W., Drohan, W.N. (eds) Recombinant Technology in Hemostasis and Thrombosis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3698-7_10

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  • DOI: https://doi.org/10.1007/978-1-4615-3698-7_10

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