Antithrombin "Chicago": a functionally abnormal molecule with increased heparin affinity causing familial thrombophilia.
A family with a high incidence of spontaneous thromboembolism over four generations has been investigated. The propositus is a 21-yr-old male with a history of thrombophlebitis. Medical histories of 46 family members were obtained. Twelve of these individuals have experienced deep venous thromboses and/or pulmonary emboli. Seven members of the kindred, with a prior history of thrombotic phenomena, were investigated in detail. These subjects were found to have normal plasma concentrations of immunoreactive antithrombin (mean 96%), decreased plasma levels of progressive antithrombin activity (mean 50%), and greatly reduced amounts of plasma heparin cofactor activity (mean 42%). The abnormal antithrombin ("Chicago") was found to elute from heparin-Sepharose at a higher ionic strength than normal inhibitor. The functionally defective antithrombin molecules exhibit a reduced ability to neutralize thrombin in the presence or absence of heparin (approximately 10%-20% of normal). The molecular defect of this protease inhibitor thus appears to be distinct from those of previously described abnormal antithrombins.
D000328:Adult; D000990:Antithrombin III / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D001780:Blood Coagulation Tests; D002846:Chromatography, Affinity; D005260:Female; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D008297:Male; D010375:Pedigree; D010958:Plasminogen / Q000032:analysis / Q000235:genetics; D013923:Thromboembolism / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D013927:Thrombosis / Q000097:blood / Q000235:genetics
D000990:Antithrombin III; D010958:Plasminogen; D006493:Heparin