Activated protein C resistance in patients with peripheral vascular disease

PURPOSE: The frequency of activated protein C (APC) resistance, caused by factor V R506Q gene mutation and abnormal APC ratio, in patients with peripheral vascular diseases was analyzed. METHODS: All patients electively admitted to the vascular ward unit of our tertiary care academic medical center from January 1995 through October 1996 (n = 679) were prospectively analyzed using an APC-resistance screening test to determine the frequency of abnormal APC ratio (< or =2.6). Baseline activated partial thromboplastin time (APTT) and its prolongation after the addition of a standard amount of APC were determined. The factor V R506Q gene mutation (Leiden) was analyzed in patients with an APC ratio less than 3.0. Statistical comparisons were made to an age-matched control population (n = 278). RESULTS: The factor V Leiden gene mutation or abnormal APC ratio was detected in 154 of the patients (22.7%), compared with 34 of 278 the control subjects (12.2%; t = 13.65; P < .001). The factor V Leiden gene mutation was found in 102 patients (15.2%), compared with 29 control subjects (10.4%; t = 4.64; P < .05); an abnormal APC ratio was found in 132 patients (19.8%), compared with 26 (9.8%) of controls (t = 14.56; P < .001). The frequency of the factor V Leiden gene mutation was significantly increased in patients with femoro-popliteal occlusive disease (n = 126), to 21.6% (t = 16.94; P< .001), and venous disease (n = 50), to 36.0% (t = 20.93; P< .001). Overall, 63% of the patients with abnormal APC ratios tested positive for the factor V Leiden gene mutation. A significantly increased frequency of APC resistance was demonstrated in patients undergoing aorto-iliac (n = 37) or femoro-crural graft reconstructions (n = 72); it was found in 41% and 35%, respectively (P < .001). In addition, a significantly increased frequency of APC resistance was found in patients who suffered from occlusion after reconstruction; 13 of 41 (32%) had the factor V Leiden gene mutation (P < .001), and 19 of 39 (49%) had an abnormal APC ratio (P < .001). CONCLUSION: The factor V Leiden gene mutation and abnormal APC ratios are significantly increased in patients with lower extremity peripheral vascular disease and failed reconstructions. An abnormal APC ratio was seen without factor V Leiden gene mutation in 37% of patients with peripheral vascular diseases, suggesting additional causes of an abnormal APC ratio, exclusive of gene mutation