RESISTANCE TO ACTIVATED PROTEIN-C - A COMMON INHERITED CAUSE OF VENOUS THROMBOSIS

Resistance to activated protein C (RAPC) is a newly recognized hyperco agulable state that was first described in 1993. It has become apparen t that RAPC is even more common than deficiencies in protein C, protei n S, or antithrombin III (AT-III) and affects an estimated 5% of the g eneral population. The majority of patients with RAPC have an abnormal ity in factor V (Arg506Gln), which renders factor Va resistant to degr adation by activated protein C. Studies in 75 patients referred to the Hematology Laboratory at Waiter Reed Army Institute of Research (WRAI R) over a 14-month period for evaluation of venous thromboembolism wer e reviewed to determine the percentage of those with RAPC, Of the 75 p atients in the study, one was deficient in protein S, one was deficien t in protein C, and none was deficient in AT-III. in contrast, 27 (36% ) patients tested positive for RAPC. Blood was available for DNA analy sis in 15 patients with RAPC. Of these 15 patients, nine (60%) tested positive for the Arg506Gln mutation in factor V. Six other patients wi th RAPC did not have the factor V mutation. Additional risk factors fo r thrombosis were immobility, obesity, use of oral contraceptives, and pregnancy. The majority of patients had deep venous thrombosis of the lower extremities; 71% had a recurrence if not placed on chronic anti coagulation therapy, Thus RAPC is a significant risk factor for venous thrombosis. Evaluation for inherited hypercoagulable states should in clude testing for this newly described condition.