Assessment of the Clinical Benefit of Prophylactic Platelet Transfusion in Thrombocytopenia Using Novel Methodology To Measure Thrombus Formation and Thrombin Generation

Patients developing severe thrombocytopenia during chemotherapy treatment are prophylactically transfused with platelets. Two novel methods were developed for measuring improved hemostasis in thrombocytopenic patients and to identify patients with aberrant responsiveness. In whole blood, platelet adhesion and thrombus formation on collagen was measured under flow. In platelet-rich plasma, platelet-dependent coagulation was assayed by automated measurement of thrombin generation. Thirty-eight thrombocytopenic patients were transfused with platelets stored in plasma or synthetic medium (PASII), and the transfusion effect on hemostatic activity was evaluated. Experimental conditions were established, where the outcome of flow and thrombin generation tests linearly increased with the platelet concentration (R2=0.98, p=0.001 and R2=0.98, p=0.008 respectively), and informed on the activation properties of platelets. In 35 out of 38 patients, transfusion with platelets in plasma or synthetic medium resulted in increased adhesion and thrombus formation under flow, and in increased platelet-dependent coagulation. The increase in platelet count after transfusion predicted 57% (P=0.001) of the improvement in function. Transfusion with platelets in plasma or synthetic medium increased the hemostatic activity with 0.63±0.30% and 0.68±0.48%, as determined with either platelet function test, with subtle differences between the two storage media. In acute graft-versus-host-disease, platelet-dependent coagulation was higher than in other patients, while thrombus formation was normal. In conclusion, altered thrombus formation and/or aberrant coagulation at low platelet counts can be detected with these novel developed and validated techniques.