Screening of Factor V Leiden (FVL) and Risk-Assessment of Venous Thrombosis in Non-FVL-Carriers: Comparison of Different Methods for Activated Protein C Resistance (APCR) Measurement

Abstract number: P1267

Guerrero¹ F, Nguyen¹ F, Inguenaud¹ C, Arnaud² C, Sié¹ P, Boneu¹ B

¹¹Laboratoires d'Hématologie, CHU de Toulouse, France ²²Département d'Epidemiologie CHU de Toulouse, France

Objective:  Activated protein C resistance (APCR) caused by FVL mutation is a risk factor for venous thrombosis (VT), but APCR remains a significant risk factor in non-FVL-carriers. In order to compare the performances of the original aPTT-based and of two modified methods of APCR measurement, we performed a case-control study in 226 patients with a documented history of VT, sampled at least 6 months after the last thrombotic episode without anticoagulant treatment, and 214 age- and sex-matched controls.

Methods:  APCR was measured using a standard aPTT assay (Coatest APCR-IL; test A), a modified aPTT assay using FV deficient plasma (Coatest APCR-V-IL; B) and a venom clotting assay using FV deficient plasma (Staclot APCR-Stago; C). The results were analysed as continuous variables using ROC curve analysis and the area under curves (AUC) were calculated.

Results:  (1) For screening FVL mutation, found in 16% of patients and 1.4% of controls, ROC curve analysis indicated that assays B and C were superior to A. Using the cut-off provided by the manufacturer, the sensitivities for FVL were 89%, 100% and 97% for A, B and C respectively. (2) The best association with the history of thrombosis was found for test A (AUC: 0.76, 0.64 and 0.59 for A, B and C, respectively; P < 0.0001). After exclusion of subjects with FVL and/or oestrogen therapy, the AUC of test A was unchanged (0.74), but those of B and C fell to 0.59 and 0.50 respectively. (3) In non-carrier patients, test A was related to FVIII:C, but not to FV levels or fV A4070G polymorphism. (4) APCR (test A) remained significantly associated to thrombosis in subjects with FVIII:C > 150 U/dL.

Conclusions:  Screening FVL and thrombosis risk-assessment in non-carriers are different objectives, which are not optimally reached by the same APCR assays.