Increased incidence of venous thrombosis in patients with shortened activated partial thromboplastin times and low ratios for activated protein C resistance

A cohort of 69 hospital patients with shortened activated partial thromboplastin time (APTT) were prospectively identified and were further investigated for resistance to activated protein C (APC). This was quantified by APTT-based and Russel viper venom time (RVVT)-based methods. The prevalence of objectively confirmed venous thromboembolism (VTE) in this cohort was 19% (13/69). Of these 69 patients, 28 also had low APC resistance ratios and the incidence of VTE among these patients (group 1) was 36% (10/28). This was significantly higher (P=0.003) than that in the remaining 41 patients (group 2) with shortened APTT and normal APC resistance (7%, 3/41). DNA analysis confirmed 13 of the group 1 patients were FV Leiden positive. The incidence of VTE in the FV Leiden group (group 1a, n=13) was 38% (5/13) and in the group whose abnormal resistance to APC was independent of FV Leiden (group 1b, n=15) was 33% (5/15). These results suggest that a shortened APTT, coexisting with a low APC resistance ratio, regardless of FV Leiden carriership status, is a marker for VTE. Increased resistance to the anticoagulant activity of APC is multifactorial as reflected by evidence of abnormal resistance differing in the two assays.