THE PREVALENCE OF POOR ANTICOAGULANT RESPONSE TO ACTIVATED PROTEIN-C (APC RESISTANCE) AMONG PATIENTS SUFFERING FROM STROKE OR VENOUS THROMBOSIS AND AMONG HEALTHY-SUBJECTS

A poor anticoagulant response to activated protein C (APC) in an activ ated partial thromboplastin time (aPTT? assay (APC resistance) was rec ently reported to be a cause of familial thrombophilia. The response t o APC was measured in 30 patients suffering from juvenile or recurrent stroke, in 40 patients suffering from venous thromboembolism and in 5 0 healthy subjects. The prevalence of APC resistance was found to be s ignificantly higher among patients with stroke (20%, P < 0.003) and ve nous thrombosis (17.5%, P < 0.02) compared with the prevalence of APC resistance among normal controls (2%). In one case of venous thrombosi s, the proposita's family (A) could be investigated and in five out of nine investigated members (56%) a poor or borderline response to APC was detected. The family (B) of another APC-resistant patient revealed six subjects with poor coagulation response to APC out of eight famil y members studied (75%). Measuring protein S activity with an automate d calcium-thromboplastin-based protein S activity assay, a significant correlation (P < 0.0001) between the results of this functional prote in S assay and APC resistance (represented by the ratio (Rs value) of clotting time with and without addition of activated protein C) was ob served. Nine out of 14 patients (64%) with poor APC response showed pr otein S activities below the normal range. Assessment of protein S act ivity with a second protein S clotting assay using factor Va as substr ate confirmed only 47% of the decreased levels of the thromboplastin-b ased protein S clotting assay. It is concluded that unless more data c oncerning the new APC cofactor become available, protein S clotting as says should be considered to be influenced by the new APC-resistance p henomenon and may not therefore be specific for protein S.