RESISTANCE TO ACTIVATED PROTEIN-C IN 9 THROMBOPHILIC FAMILIES - INTERFERENCE IN A PROTEIN-S FUNCTIONAL ASSAY

Nine thrombophilic patients who had had previous diagnoses of function al protein S deficiency were reinvestigated. The functional protein S assays gave dose-response curves that were not parallel to those of th e reference plasma. The same pattern was true for approximately half o f the first-degree relatives of the propositi. When protein S was extr acted from the plasma of the patients by immunoabsorption, it had a no rmal ratio of functional activity to immunologic concentration. Restri ction fragment length polymorphism analysis, informative in one family , showed no linkage between the protein S gene marker and the abnormal behavior of the protein S functional assay. All the propositi and. 23 /36 first-degree relatives were resistant to the prolongation of activ ated partial thromboplastin time induced by activated protein C. Furth ermore, there was striking concordance in all patients and relatives b etween the abnormal pattern of the protein S functional assay and resi stance to activated protein C. We conclude that a plasma-based functio nal protein S assay is sensitive to activated protein C resistance and this may lead to spuriously low results in the assay. In agreement wi th the results of others, this study indicates that resistance to acti vated protein C is a frequent hemostatic defect in selected thrombophi lic populations.