Novel methodology for assessment of prophylactic platelet transfusion therapy by measuring increased thrombus formation and thrombin generation.

Currently, patients developing severe thrombocytopenia during chemotherapy treatment are prophylactically transfused with platelets. We developed two platelet function tests to report the improved haemostasis in the transfused patients, which were capable of detecting aberrant responsiveness of the platelets after transfusion. First, in a whole-blood flow test, platelet adhesion and thrombus formation were determined under high-shear flow conditions. Second, the procoagulant function of platelets was assayed in platelet-rich plasma by measurement of thrombin generation. Experimental conditions were established, where flow-induced adhesion and thrombin generation test parameters increased semi-linearly with the platelet concentration, and informed on the activation properties of platelets. The transfusion effects were evaluated for 38 thrombocytopenic patients, who were transfused with platelets stored in plasma or in synthetic medium (platelet additive solution II). In most but not all patients, transfusion resulted in increased adhesion and thrombus formation, as well as in improved platelet-dependent coagulation. Taken together, the increase in platelet count after transfusion explained 57% of the overall improvement in platelet function. In acute graft-versus-host disease, thrombus formation was normal, while platelet-dependent coagulation was higher than expected. We conclude that assessment of flow-induced adhesion and thrombin generation in acquired thrombocytopenia adequately determines the improved haemostatic activity by transfused platelets.