A modification of the APC resistance test and its application to the study of patients on coumarin therapy

Abstract APC resistance appears to be caused, predominantly, by a mutation in coagulation factor V (nucleotide 1691: G to A). This phenomenon is usually studied by performing APTTs in the absence and presence of added APC. We studied a modification of the assay involving dilution of the test plasma in factor V deficient plasma, to render the assay more factor V specific. This modification was applied to 76 patients with venous thrombosis on coumarin treatment and to 45 controls. Two out of 45 controls (4.4%) showed abnormal results with the modified test. They also showed loss of factor V exon 10 Mnl I restriction site, associated to APC resistance. All remaining controls, with normal functional results by the modified assay, showed normal restriction profile. We detected 9 affected patients (11.8%), one of them homozygous or double heterozygous. In conclusion, the modified assay is very sensitive for factor V dependent APC resistance, and can successfully be applied to patients on coumarin therapy.