Indirect antiplatelet effects of rivaroxaban in a patient with intracranial hemorrhage: An underappreciated coagulopathy of factor Xa inhibitors?

Rivaroxaban is a direct oral anticoagulant (DOAC) used for prophylaxis and treatment of many prothrombotic states. The anticoagulation effects of rivaroxaban are produced by selectively binding and inhibiting factor Xa, causing delayed thrombin generation. Additionally, the delay in thrombin generation produces an indirect, dose dependent antiplatelet effect via reduction in tissue factor platelet aggregation. As with any anticoagulant, rivaroxaban use increases a patient's risk for major and minor hemorrhagic events. With mortality rates reported as high as 25% for those who experience an intracranial hemorrhage (ICH), immediate mitigation of hematoma and hemorrhage volume expansion is imperative. Management strategies include utilizing prothrombin complex concentrates (PCC) and factor Xa inhibitor specific antidotes, such as coagulation factor Xa recombinant, inactivated-zhzo. Routine monitoring or management of DOAC induced antiplatelet effects is ill-defined and not a part of routine standard of care. We report the first case, to our knowledge, of rivaroxaban's indirect antiplatelet effects identified by platelet function assays and managed with four-factor PCC and desmopressin in a patient experiencing an ICH. Further exploration is needed to determine the true clinical impact attributed to rivaroxaban's antiplatelet effects.