A comparison between two activated protein C resistance methods as routine diagnostic tests for factor V Leiden mutation.
The most common commercially available test measuring activated protein C (APC) resistance relies on the the anticoagulant response to added APC in an activated partial thromboplastin time (APTT) based method. Another method is a Russell Viper venom time (RVVT) based system. To improve the specificity for factor V Leiden of the APTT based method, pre-dilution of test plasma in FV-deficient plasma has recently been recommended. In this study we tested the relative suitabilities of the APTT-based system, the RVVT-based system and their corresponding assays modified by pre-dilution in FV-deficient plasma, for screening asymptomatic subjects, a group of thrombophilic patients (in particular those with low APC ratios), patients on oral anticoagulants, and patients with lupus anticoagulant (LAC). We found the RVVT-based assay to be superior to the APTT-based method in the separation of normals from those with FV Leiden mutation both in asymptomatic subjects and in the thrombophilic patient group. Both modified assays demonstrated a sensitivity and specificity of 100% for FV Leiden, as verified by genotyping in asymptomatic subjects, thrombophilic patients and patients on oral anticoagulants, with the modified RVVT-based assay giving better separation between normals and FV Leiden. Inhibition of phospholipid-dependent coagulation by LAC antibodies rendered the APTT-based system less suitable than the phospholipid-rich RVVT-based one, and as nine of the 20 LAC-positive patients were on warfarin, we showed only the modified RVVT assay to be a reliable predictor of factor V Leiden in this patient group.
Aboud
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MR
Department of Haematology, Royal North Shore Hospital, Sydney, N.S.W., Australia.
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D000328:Adult; D005165:Factor V / Q000235:genetics*; D005260:Female; D006801:Humans; D016682:Lupus Coagulation Inhibitor / Q000097:blood; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010314:Partial Thromboplastin Time; D011486:Protein C / Q000032:analysis*; D011517:Prothrombin Time; D012680:Sensitivity and Specificity; D013927:Thrombosis / Q000097:blood / Q000175:diagnosis*; D014859:Warfarin / Q000627:therapeutic use
D016682:Lupus Coagulation Inhibitor; D011486:Protein C; C095381:factor V Leiden; D014859:Warfarin; D005165:Factor V