Activated protein C resistance: Prevalence and implications in peripheral vascular disease

Purpose: Activated protein C (APC) is a naturally occurring anticoagulant that interacts with factors V and VIII to inhibit the clotting cascade. Resistance to APC (APC-R), hypothesized to occur as a result of an abnormal factor V, has been documented in up to 40% of patients with venous thrombotic events, but its prevalence in patients with arterial disease remains ill defined. Methods: With an assay of APC resistance that expresses the ratio of the activated partial thromboplastin time with and without the addition of exogenous APC, APC resistance ratios were quantitated in 200 individuals comprising 177 patients with vascular disease and 23 control subjects. An abnormal activated partial thromboplastin time was present in four patients who were excluded from analysis. The 173 remaining patients formed the study population and were divided into diagnostic subgroups on the basis of the most symptomatic problem. Results: APC resistance was documented in 20 individuals, representing 11.6% of the study group. The highest prevalence of APC resistance was observed in patients with lower extremity occlusive disease, with the APC-R ratio below 2.0 in 13.7%. Within the subgroup of individuals with lower extremity disease, 76 patients (10 with APC-R, 13.2%) underwent infrainguinal bypass and were monitored a mean of 47 +/- 8 months. Occlusion of the arterial reconstruction occurred in 22 patients (29%). Six (60%) of the patients with APC-R had failed reconstructions, versus 16 (24%) of 66 patients without APC-R (p = 0.02). Conclusions: These findings suggest that APC-R is relatively common in patients with peripheral vascular disease, especially in those with lower extremity occlusive disease. APC-R appears to be a risk factor for failure of infrainguinal bypass. These observations suggest that screening for APC-R may be useful in patients with peripheral vascular disease, providing the opportunity to restore the normal thrombogenic balance with anticoagulant therapy in susceptible individuals.