A MODIFICATION OF THE APC RESISTANCE TEST AND ITS APPLICATION TO THE STUDY OF PATIENTS ON COUMARIN THERAPY

APC resistance appears to be caused, predominantly, by a mutation in c oagulation factor V (nucleotide 1691: G to A). This phenomenon is usua lly studied by performing APTTs in the absence and presence of added A PC. We studied a modification of the assay involving dilution of the t est plasma in factor V deficient plasma, to render the assay more fact or V specific. This modification was applied to 76 patients with venou s thrombosis on coumarin treatment and to 45 controls. Two out of 45 c ontrols (4.4%) showed abnormal results with the modified test. They al so showed loss of factor V exon 10 Mnl I restriction site, associated to APC resistance. All remaining controls, with normal functional resu lts by the modified assay, showed normal restriction profile. We detec ted 9 affected patients (11.8%), one of them homozygous or double hete rozygous. In conclusion, the modified assay is very sensitive for fact or V dependent APC resistance, and can successfully be applied to pati ents on coumarin therapy.