Improving clot formation with a combination of fibrinogen concentrate and activated prothrombin complex concentrate in a model of severe thrombocytopenia

Abstract

Severe thrombocytopenia is associated with increased risk of bleeding. The bleeding symptoms vary from single petechiae to life-threatening hemorrhage. Methods for rapid restoration of hemostatic potential in severe thrombocytopenia are still limited. Aim. To investigate effects of fibrinogen concentrate and activated prothrombin complex concentrate (APCC) on clot formation in an in vitro model of severe thrombocytopenia. Methods. Citrated whole blood from adult healthy volunteers was centrifuged to obtain platelet-rich plasma, platelet-free plasma, and packed cells. To create the model of severe thrombocytopenia, the blood components were mixed at a predefined ratio. Mean platelet count in the reconstituted blood was 16 x 10⁹ L^-1. In a separate series of experiments, thrombocytopenic blood was diluted with Tris-buffered saline and treated with tissue plasminogen activator to induce hyperfibrinolysis. To correct coagulopathy, blood was spiked with fibrinogen concentrate and/or APCC. Clotting was induced by recalcification and addition of tissue factor. Clot formation and lysis were monitored using rotation thromboelastometry. Results. Spiking of thrombocytopenia blood with APCC shortened the clotting time while spiking with fibrinogen increased the rate of clot formation and maximal clot firmness; no additive or synergistic effect was observed when both agents were used together. In the model of severe thrombocytopenia complicated with hemodilution and hyperfibrinolysis, both fibrinogen and APCC reduced
the clotting time, increased the rate of clot formation and maximal clot firmness, and delayed the onset of clot lysis; when used together, the agents produced an additive effect further improving clot formation and fibrinolytic resistance of the clot. Conclusion. The use of fibrinogen concentrate and APCC may potentially serve as an alterna tive to platelet transfusion and be beneficial for the treatment of patients with severe thrombocytopenia complicated or not with hyperfibrinolysis and hemodilution.