HETEROGENEITY OF THE APC-RESISTANCE PHENOMENON

We developed an amidolytic assay for the determination of APC-resistan ce by inhibition of factor Xa (F Xa) generation, expecting it to be a result of factor VIIIa (F VIIIa) inactivation. Thirty-nine samples wer e tested with the proposed assay and compared to an APTT-based assay p erformed using the APC-resistance kit (Chromogenix, Molndal, Sweden). In both assays APC was added at the last stage of the reaction togethe r with CaCl2. The response to APC was calculated as a ratio of absorba nces (or of clotting times) of a sample tested with or without APC and as the amount of F VIII activity generated in the presence of APC. An APC-ratio less than 2.0 and residual F VIII activity over 55% indicat ed APC-resistance. The results demonstrated that APC-response was hete rogenic and dependent on the assay used for the determination. Only 1/ 3 of the tested samples were resistant in both APTT-based and in amido lytic assays. A number of samples developed an adequate decrease in F VIII activity, but the APC-resistance was still registered by the APTT -based assay. Other samples had a sufficient APC-response in APTT-base d assay, in spite of diminished inactivation of F VIIIa. The obtained data presented the response to APC as a complex process with a chain o f reactions. It indicated that poor degradation of coagulation factors may not be sufficient for its development.