Activated protein C resistance (APCR), measured using the original assay described by Dahlbäck, is a risk factor for
venous thrombosis independent of the
factor V Leiden (FVL) mutation. This assay is based on the activated partial thromboplastin time (APTT) after plasma exposure to activated
protein C (APC). As this assay was sensitive to numerous interferences, new assays have been developed for FVL screening. The objectives of the study were to investigate the association of second generation assays for APCR with
venous thrombosis in FVL non-carriers. One hundred ninety-seven subjects with a history of
venous thrombosis and 211 controls were explored using 3 APCR assays, the original APTT-based assay (test A), an APTT-based assay with
factor V depleted plasma pre-dilution (test B) and a direct
factor X activation-based assay with the same pre-dilution (test C). We found that subjects with results in the lowest quartile of the APTT-based assays are at increased risk, compared to those in the highest quartile (test A Odds Ratio = 6.39; 95% CI 3.23-12.63; test B OR = 2.72; 95% CI 1.50-4.94). There was no significant risk increase associated with test C results. After adjusting for FVIII levels, the
ORs of tests A and B were similar (test A OR = 3.22; 95% CI 1.47-7.08; test B OR = 3.10; 95% CI 1.54-6.21). In conclusion, APTT-based assays, but not direct
factor X activation-based assays, effectively detect the risk for
venous thrombosis independent of FVL. Pre-dilution in
factor V depleted plasma is an effective way to directly assess the risk independent of FVIII levels.