FEIBA™ for Reversal of Direct Oral Anticoagulant Associated Major Bleeding

Abstract Introduction: Direct oral anticoagulants (DOACs) are indicated for the prevention of systemic embolism in patients with atrial fibrillation and for the prevention and treatment of venous thrombosis. Although DOACs offer advantages over the vitamin K antagonists, some hesitancy remains over their use given the lack of specific antidotes for management of life threatening bleeding events. In vivo studies, case reports and case series have shown that prothrombin complex concentrate (PCC) and activated PCC might potentially be used to control life threatening bleeding in patients with DOAC-associated bleeding episodes. Herein we describe management and outcomes of DOAC-associated life threatening bleeding events using an activated PCC (FEIBA™). Methods: A retrospective review of patients presenting with DOAC-associated (dabigatran, rivaroxaban or apixaban) life threatening bleeding to The Ottawa Hospital between January 2013 and June 2014 are included. Patients received 25 – 50 units/kg of FEIBA™. The primary outcome was adverse thrombotic and embolic events during follow-up. Secondary outcome was symptomatic control of bleeding. Results: Nine patients presented to hospital with life threatening bleeding episodes (post trauma: n=3; spontaneous bleeding: n=6). Spontaneous episodes included epistaxis or gastro-intestinal bleeding. Baseline characteristics are depicted in Table 1. A majority of patients had atrial fibrillation (n=8) and received rivaroxaban (n=5). The last dose of DOAC was taken within 24 hours of bleeding events for all patients. All patients received supportive management, interventions/procedures aimed at attaining source control of bleeding when possible, and transfusion of FEIBA™ for reversal of anticoagulant effect. Adverse events after receiving FEIBA™ were uncommon with one patient experiencing a TIA with expressive aphasia and visual field deficit on the evening of FEIBA™ transfusion; deficits resolved by the time of hospital discharge. Two patients with GI bleeding continued to have ongoing bleeding despite FEIBA™ administration and two patients died as a result of major bleeding. Conclusions: In this cohort of patients with major bleeding associated with DOACs, FEIBA™ administration, in addition to supportive care, was helpful in minimizing further complications of most bleeding events and associated with a low rate of adverse events. Prospective studies are needed to evaluate benefits and harms of FEIBA™ for management of DOAC associated major bleeding. Abstract 1540. Table 1: Patients with Life-threatening Bleeding Patient (Age and Gender) Indication for DOAC [AF(CHADS2); VTE] DOAC and Dosage Site of Bleeding Intervention/ Procedure Units of PRBCs Transfused Additional Treatment FEIBA™ Dose (IU)(1st/2nd) Adverse Events post-FEIBA™ Administration Survived Hospitalization 85 Male AF (2) Rivaroxaban 20 mg daily Epistaxis Nasal Packing 0 -- 3275 -- Yes 86 Male AF (2) Rivaroxaban 20 mg daily LGIB Angiogram, no embolization performed 10 Vitamin K 3159/ 2952 -- Yes 84 Male AF (2) Dabigatran 110 mg BID Orbital vitreous hemorrhage Surgical repair of ruptured globe 0 -- 1812 -- Yes 92 Male AF (6) Apixaban 5 mg BID Left hand Conservative management 1 Tranexamic acid 2718 TIA Yes 85 Male VTE Rivaroxaban 20 mg daily LGIB Conservative management 2 Vitamin K 1740 -- Yes 90 Female AF (5) Rivaroxaban 20 mg daily SDH Conservative management 0 -- 3275 -- No; died of major bleed 93 Female AF (6) Apixaban 2.5 mg BID LGIB Conservative management 4 -- 2241 -- No 93 Male AF (3) Rivaroxaban 15 mg daily UGIB Upper endoscopy, no intervention 4 Vitamin K 3000 -- No; died of major bleed and septic shock 81 Male AF (4) Dabigatran 110 mg BID LGIB Upper endoscopy and colonoscopy, no interventions 4 -- 3362 -- No AF = atrial fibrillation; BID = twice daily; CHADS = congestive heart failure, hypertension, age, diabetes, stroke; DOAC = direct oral anticoagulant; IU = international units; LGIB = lower gastrointestinal bleeding; PRBC = packed red blood cells; SDH = subdural hematoma; TIA = transient ischemic attack; UGIB = upper gastrointestinal bleeding; VTE = venous thromboembolism Disclosures Off Label Use: FEIBA is an activated prothrombin complex concentrate that was used during management of life threatening bleeding in patients with direct oral anticoagulant-associated bleeding episodes..