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.