Hypercoagulable states. Ann Intern Med 1993 Oct 15;119(8):819-27
Date
10/15/1993Pubmed ID
8379603DOI
10.7326/0003-4819-119-8-199310150-00008Scopus ID
2-s2.0-0027729107 (requires institutional sign-in at Scopus site) 197 CitationsAbstract
PURPOSE: To describe the major pathophysiologic mechanisms underlying inherited and secondary hypercoagulable states and to evaluate the frequency, natural history, diagnosis, and management of the various clinical disorders.
DATA SOURCES AND STUDY SELECTION: Relevant clinical literature obtained from bibliographies in hematology textbooks and from computerized indexes was reviewed. A hypothesis was formed based on this literature review and on recent developments from a number of experimental studies.
DATA SYNTHESIS: Hypercoagulable states include various inherited as well as acquired clinical disorders characterized by an increased risk for thromboembolism. Primary hypercoagulable states include relatively rare inherited conditions that lead to disordered endothelial cell thromboregulation. These conditions include decreased thrombomodulin-dependent activation of activated protein C, impaired heparin binding of antithrombin III, or down-regulation of membrane-associated plasmin generation. The major, inherited, inhibitor disease states include antithrombin III deficiency, protein C deficiency, and protein S deficiency and should be considered in patients who have recurrent, familial, or juvenile deep-vein thrombosis or occlusion in an unusual location such as a mesenteric, brachial, or cerebral vessel. Secondary hypercoagulable states may be seen in many heterogeneous disorders. In many of these conditions, endothelial activation by cytokines leads to loss of normal vessel-wall anticoagulant surface functions with conversion to a proinflammatory thrombogenic phenotype. Important clinical syndromes associated with substantial thromboembolic events include the antiphospholipid syndrome, heparin-induced thrombopathy, the myeloproliferative syndromes, and cancer.
CONCLUSIONS: Physiologic thromboregulation occurs at the vessel-wall surface. Quantitative and qualitative deficiencies of normal, steady-state endothelial anticoagulant activities are associated with primary hypercoagulable states. Activated endothelial cell surfaces express a thrombogenic phenotype and contribute to secondary or acquired hypercoagulability.
Author List
Nachman RL, Silverstein RAuthor
Roy L. Silverstein MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Blood Coagulation DisordersHumans
