A MODIFIED FUNCTIONAL GLOBAL TEST TO MEASURE PROTEIN-C, PROTEIN-S ACTIVITIES AND THE ACTIVATED PROTEIN C-RESISTANCE PHENOTYPE

Identifying a defect affecting the protein C/protein S (PC/PS) anticoa gulant system, using a single global test, has recently become possibl e thanks to a new methodological approach based on the activation of e ndogenous plasma PC by Protac(R), derived from Agkistrodon Contortix s nake venom (ACV). The introduction of a commercial test (ProC(R)Global ), ACV-based, provides a useful tool for the screening of thrombotic p atients since the most frequent: causes of inherited thrombophilia are found in the PC/PS system. The test provides information only on the global activity of the anticoagulant pathway but not on PC and PS acti vity or on the factor V related conditions (e.g., FV Leiden). The pres ent study shows that by carrying out the test alternating the presence of PC-, PS-, or FV-deficient plasma and using appropriate amounts of ACV, it is possible to increase the specificity of the test to correct ly evaluate respectively the PC or PS activities or the activated prot ein C resistance condition (APC-R). These simple modifications applied to the original commercial test allow to detect exactly, using a sing le, basic methodology, the principal defects affecting the PC/PS antic oagulant pathway. Furthermore, carrying out the tests on an automated coagulometer, in combination or not with the classic ProC(R)Global ass ay, it is possible to use a unique reagent profile to simultaneously i nvestigate in the same or different samples, the PC, PS, and APC-R def ect. (C) 1998 Elsevier Science Ltd.