Characteristics, management, and outcomes of patients who received off-label activated prothrombin complex concentrate (aPCC) for reversal of an apixaban or rivaroxaban acute bleeding event were evaluated in a single-center study. The results were presented by John Koerber, PharmD, of Beaumont Health in Royal Oak and Wayne State University in Detroit, Michigan, and colleagues at the Thrombosis & Hemostasis Summit of North America (THSNA) 2020 Virtual Conference.

“Although an FDA-approved reversal agent is available for apixaban and rivaroxaban bleeding, the anticoagulation reversal protocol at our institution recommends activated prothrombin complex concentrate,” wrote the authors.

The single-center, retrospective cohort study evaluated patients who received aPCC for acute apixaban or rivaroxaban bleeding at Beaumont Hospital between August 2016 and July 2019. The investigators obtained a variety of patient and clinical information and outcomes, including in-hospital thrombotic event rate, mortality, and anticoagulation resumption. Post hospital discharge 30-day thrombosis and mortality were also assessed. 

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Overall, the 77 patients who were taking a direct Xa inhibitor anticoagulant (58.4% apixaban, 41.6% rivaroxaban) and received aPCC for reversal due to an acute bleeding event were identified. The patients had a mean age of 75.7±11.5 years and mean total body weight of 79.9±17.2 kg. In terms of comorbid conditions, 32.5% had chronic kidney disease, 27.3% had a current episode of acute kidney injury, 2.6% had hepatic dysfunction, and 23.4% had thrombocytopenia. The patients were administered a median aPCC dose of 32.6 units/kg.

The investigators found that 15.6% of patients had been prescribed an inappropriate anticoagulant dose, and in half of those patients (6 patients), the dose was considered to be too high (7.8%). Additionally, 54.5% of patients were receiving concurrent antiplatelet therapy.

Major bleeding occurred in 94.8% of patients (73/77), and clinically relevant nonmajor bleeding occurred in 4 patients. Patients had bleeding in the following locations: 44.2% intracranial, 22.1% gastrointestinal, and 33.7% other.

Within the cohort, 90.9% of patients had diagnostic testing, and 28.5% of patients underwent bleed management procedures, including surgery (8 patients, 10.4%). Packed red blood cells were used in 45.5% of patients; however, 100% of patients with gastrointestinal bleeding received them. Fresh frozen plasma was administered to 19.5% of patients.

During the hospital stay, 9.1% of patients experienced thrombotic events, and within 30 days of discharge, 2 patients had thrombotic events (total 9 patients, 11.7%). At discharge, 19.5% of patients (15 patients) had died and 30 days after discharge, 21 patients died (27.3%; all-cause mortality data was unavailable for 8 patients). At discharge, 28.6% of patients resumed therapeutic anticoagulation.

“This study provided a real-world picture of patients receiving aPCC for the reversal of apixaban or rivaroxaban-associated acute bleeding event,” wrote the authors. “The use of fresh frozen plasma in nearly 20% of patients suggest clinician education regarding appropriate bleed management strategies in those with direct Xa inhibitor bleeding is needed.”


Koerber JM, Fritsch K, Hoffman JL, et al. Characteristics, management, and outcomes of patients receiving activated prothrombin complex concentrate for apixaban and rivaroxaban associated major bleeding. Abstract presented at: THSNA 2020 Thrombosis & Hemostasis Summit of North America; October 27-30, 2020. Abstract 103.