title: Comparison of three activated protein C resistance tests in the risk assessment of venous thrombosis in non-carriers of the factor V Leiden mutation.
abstract: 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.
authors.affiliation: Laboratoire de Recherche sur la Thrombose, EA 2049, Hôpital Rangueil, Toulouse cedex, France.
authors.forename: Felipe
authors.initials: F
authors.lastname: Guerrero
authors.forename: Catherine
authors.initials: C
authors.lastname: Arnaud
authors.forename: Francoise
authors.initials: F
authors.lastname: Nguyen
authors.forename: Bernard
authors.initials: B
authors.lastname: Boneu
authors.forename: Pierre
authors.initials: P
authors.lastname: Sié
mesh_terms: D020016:Activated Protein C Resistance / Q000378:metabolism*; D000328:Adult; D001780:Blood Coagulation Tests / Q000379:methods*; D016022:Case-Control Studies; D005165:Factor V / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012307:Risk Factors; D020246:Venous Thrombosis / Q000235:genetics / Q000473:pathology*
chemical_list: C095381:factor V Leiden; D005165:Factor V