Background In three families with various forms of venous thrombosis,we observed an apparently inherited poor response to the anticoagulantactivated protein C (APC). The condition was due to a deficiencyin a previously unrecognized anticoagulant factor that functionedas a cofactor to activated protein C.
Methods We conducted the present study to determine the prevalenceof resistance to APC in patients with venous thrombosis. Wecompared 104 consecutive patients with venous thrombosis confirmedby objective tests with 130 controls. In addition, 211 membersof 34 families of persons with resistance to APC were studied.The anticoagulant response to APC was measured with a modifiedversion of the activated partial-thromboplastin time test; theresults were expressed as APC ratios.
Results Forty-five percent of patients had a family historyof thrombosis. A significant (P<0.001) difference in APCratios was observed between the controls and the patients withthrombosis. For 33 percent of patients, the APC ratio was belowthe 5th percentile of the control values, although the resultsof the family studies suggested that the prevalence of APC resistancemay be even higher (approximately 40 percent) in the patientswith thrombosis. The inherited nature of the defect was confirmedin a majority of cases, and the family studies suggested themode of inheritance to be autosomal dominant. The thrombosis-freesurvival of APC-resistant family members was significantly lessthan that of non-APC-resistant family members.
Conclusions There was a high prevalence of APC resistance amongyoung persons with a history of venous thrombosis, and thisresistance appeared to be inherited as an autosomal dominanttrait.
Source Information
From the Department for Coagulation Disorders (P.J.S., B.D.), the Department of Medicine (P.J.S.), and the Department of Clinical Chemistry (B.D.), University of Lund, Malmo General Hospital, Malmo, Sweden. Presented in part at the 14th Congress of the International Society on Thrombosis and Haemostasis, New York, July 4-9, 1993.
Address reprint requests to Professor Dahlback at the Department of Clinical Chemistry, Malmo General Hospital, S-214 01 Malmo, Sweden.
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