Summary
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 factorV depleted
plasma pre-dilution (test B) and a direct factorX 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.
Keywords
Venous thrombosis - activated protein C resistance - factor V Leiden - factor VIII