Syndromes of thrombosis and hypercoagulability: Congenital and acquired thrombophilias

This article stresses the common hereditary and acquired blood protein defects associated with thrombosis. The most common of the hereditary defects apear to be APC-R, SPS, antithrombin, protein C, and protein S deficiency, and the most common acquired defects are anticardiolipin antibodies and the lupus anticoagulant (antiphospholipid antibodies). Therefore, these are the defects that should first be looked for in an individual with unexplained thrombosis. If these more common defects are not found, then the rarer defects including HC II, plasminogen or TPA deficiency, dysfibrinogenemia, elevated PAI-1 and hyperhomocysteinemia should be sought. The importance of finding these defects has significant implications for therapy of the individual patient and for institutions of family studies to identify, inform, and possibly treat others at risk. It is expected that as knowledge of hemostasis expands, more hereditary and acquired defects, such as elevated lipoprotein (a) or defects of extrinsic (tissue factor) pathway inhibitor (EPI, TFPI), may be associated with enhanced risks of thrombosis. Finally, it must be recalled that a diagnosis of thrombosis, like that of anemia, is only a generic and partial diagnosis; just as in the anemic patient, the etiology must be clearly defined. Only in this manner can cost-effective and appropriate therapy for both primary treatment and secondary prevention be designed. In addition, the demonstration of a hereditary defect will allow primary prevention in afflicted family members by allowing the choice of appropriate therapy.