Category: Professional Posters
Purpose: The use of direct oral anticoagulants (DOACs) has increased due to guideline recommendations and expanded indications. Bleeding related to DOAC use is a serious adverse effect. Despite approval of coagulation factor Xa (recombinant), inactivated-zhzo, a specific reversal agent for apixaban and rivaroxaban, the debate regarding the optimal treatment strategy for bleeding associated with factor Xa inhibitors is unsettled. Four-factor prothrombin complex concentrate (4F-PCC) is commonly used off-label for treatment of serious bleeding in patients receiving DOACs. The purpose of this medication use evaluation is to evaluate the efficacy and safety of using 4F-PCC in the management factor Xa inhibitor-associated bleeding.
Methods: A retrospective chart review was completed using the hospital’s electronic medical record. All patients who received 4F-PCC to manage apixaban or rivaroxaban-associated bleeding from June 2018 to April 2019 were included. Data collected included patient demographics, pre-admission DOAC, concomitant medications, source of bleeding, 4F-PCC dose, and adjunctive hemostatic therapy (e.g., desmopressin, tranexamic acid, blood products). The primary efficacy outcome was achievement of adequate hemostasis following 4F-PCC administration. Effective hemostasis was defined as not requiring any additional hemostatic agents, coagulation factors, or blood products more than 48 hours after receiving 4F-PCC for any type of bleeding. In addition, bleeding-site specific requirements for effective hemostasis as defined by the International Society on Thrombosis and Hemostasis were incorporated into the assessment. Non-visible bleeding (e.g., gastrointestinal) was considered to have effective hemostasis if the patient’s hemoglobin was stable (no more than 10% reduction) at 48 hours and visible bleeding required cessation within four hours. Musculoskeletal bleeding required improvements in pain and swelling at 24 hours. Effective hemostasis of intracranial hemorrhage was evaluated using physician documentation based on computed tomography. Length of stay, as well as rates of thrombosis and mortality were also evaluated. Descriptive statistics were used to analyze the data.
Results: Seventeen patients received 4F-PCC for apixaban (n=16) or rivaroxaban (n=1) associated bleeding. The cohort was 66% male with an average age of 77 years. Atrial fibrillation was the anticoagulation indication for 87% of patients. Concurrent home antiplatelet therapy included aspirin (n=7) and dual therapy with aspirin and ticagrelor (n=1). Patients received either 50 units/kg (87%) or 25 units/kg (13%) of 4F-PCC. Hemostatic efficacy was unable to be evaluated in two patients as they were transferred to a tertiary hospital soon after admission. Of the fifteen patients evaluable for hemostatic efficacy, the site of the bleed was intracranial (n=7), gastrointestinal (n=6), paravertebral (n=1), and pericardial (n=1). Hemostatic efficacy was achieved in 14/15 (93%) patients. The single patient with inadequate hemostasis had a gastrointestinal bleed complicated by disseminated intravascular coagulopathy requiring additional hemostatic interventions. Two patients (13%) died and no patient experienced a thrombotic event during hospital admission.
Conclusion: In this retrospective study, 4F-PCC appears to provide adequate hemostasis for apixaban-associated bleeding without increasing the risk for thrombosis. No conclusions can be drawn regarding rivaroxaban-associated bleeding since just one patient receiving rivaroxaban was evaluated. This study is limited by the small sample size and reliance on adequate medical record documentation of hemostasis.