PB1313 - Factor V as adjunct to fibrinogen and prothrombin complex concentrate in an in vitro model of combined severe trauma-induced coagulopathy and rivaroxaban anticoagulation

Background: Prothrombin complex concentrate (PCC) is used in the off-label management of life-threatening conditions such as dilutional coagulopathy or severe and acute bleeds associated with direct oral anticoagulants. In one of our previous studies, however, PCC proved ineffective in vitro in a model of combined dilutional coagulopathy and rivaroxaban anticoagulation. We have recently reported that factor V concentrate (FVC) in addition to PCC is beneficial in vitro in the reversal of rivaroxaban anticoagulation under non-dilutional conditions.

Aims: To investigate the usefulness of FVC as adjunct to fibrinogen concentrate (FC) and PCC in an in vitro model of combined dilutional coagulopathy and rivaroxaban anticoagulation.

Methods: Severe coagulopathy was mimicked in vitro by diluting rivaroxaban-spiked whole blood with saline, tissue factor and tissue plasminogen activator. Influence of added PCC, FVC and FC as well as tranexamic acid (TXA) on clot formation (reaction time, R), clot strength (maximal amplitude, MA) and clot stability towards fibrinolytic breakdown (clot lysis time, CLT) was evaluated by thromboelastography.

Results: Whole blood dilution with saline induced a profibrinolytic state and further deteriorated the impaired hemostatic potential of rivaroxaban anticoagulated whole blood. Reduced MA was only partially corrected by FC, alone or in combination with PCC, but was almost completely normalized when FVC was also added. Prolonged clotting time did not improve by PCC and FC. The combination of FVC with PCC and FC, however, almost completely normalized R-time. Strongly reduced CLT was only partially improved by the combination of FC, PCC and FVC. TXA was required to fully restore clot stability.

Conclusion(s): FVC as adjunct to FC and PCC may be useful in complex coagulopathic conditions by normalizing clot formation. For prevention of premature clot dissolution, the presence of TXA is also needed.