In the area of clinical coagulation research, much attention is focused on the molecular events which occur before, during, and after anticoagulant and antithrombotic therapies. For purposes of monitoring the safety, efficacy and long-term effects of such therapies, there exist a number of commercially available assays to assess the progression of the procoagulant and fibrinolytic responses. For example, to monitor the procoagulant response, there exists: a) an assay for fragment 1-2 of prothrombin to monitor prothrombinase activity; and b) an assay for fibrinopeptide-A to monitor thrombin activity. The same holds true for the fibrinolytic response where assays for D-Dimer and FDP fragments of fibrin and fibrinogen respectively may be used to monitor the activity of plasmin. Unfortunately, an analogous assay to measure the progression of the anti-anticoagulant response does not exist. We believe that an assay to measure the in vivo activity of APC, by measuring the APC catalyzed inactivation of factor Va will provide a direct measure of the anticoagulant response. In this proposal we plan to develop an ELISA assay which may be used to quantitatively measure the APC catalyzed conversion of factor Va to factor Vai (inactivated factor Va).Awardee's statement of the potential commercial applications of the research:There exists a number of commercially available assays for monitoring the in vivo progression of the procoagulant and fibrinolytic responses. Currently there is no analogous assay available for monitoring progression of the anticoagulant response. Such an assay would have broad research and clinical application for monitoring the safety and efficacy of anticoagulant and antithrombotic therapy.National Heart, Lung, and Blood Institute (NHLBI)
