title: Heterogeneity of the APC-resistance phenomenon.
abstract: We developed an amidolytic assay for the determination of APC-resistance by inhibition of factor Xa (F Xa) generation, expecting it to be a result of factor VIIIa (F VIIIa) inactivation. Thirty-nine samples were tested with the proposed assay and compared to an APTT-based assay performed using the APC-resistance kit (Chromogenix, Mölndal, Sweden). In both assays APC was added at the last stage of the reaction together with CaCl2. The response to APC was calculated as a ratio of absorbances (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% indicated APC-resistance. The results demonstrated that APC-response was heterogenic and dependent on the assay used for the determination. Only 1/3 of the tested samples were resistant in both APTT-based and in amidolytic 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-based assay, in spite of diminished inactivation of F VIIIa. The obtained data presented the response to APC as a complex process with a chain of reactions. It indicated that poor degradation of coagulation factors may not be sufficient for its development.
authors.affiliation: Department of Laboratory Medicine, Karolinska Institute, Karolinska Hospital, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Bokarewa
authors.forename: M
authors.initials: M
authors.lastname: Blombäck
mesh_terms: D000328:Adult; D000577:Amides / Q000378:metabolism; D004351:Drug Resistance / Q000502:physiology; D005169:Factor VIII / Q000378:metabolism; D015951:Factor Xa / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D011486:Protein C / Q000378:metabolism*
chemical_list: D000577:Amides; D011486:Protein C; D005169:Factor VIII; D015951:Factor Xa