Prothrombin complex concentrate for direct factor Xa inhibitor-associated bleeding or before urgent surgery
Joseph R. Shaw a), Abdulrahman Abdulaziz Almujalli a), Yan Xu a), Jerrold H. Levy b), Sam Schulman c) d), Deborah Siegal a), Dar Dowlatshahi a), Melanie Tokessy e), Hakan Buyukdere e), Marc Carrier a), Lana A. Castellucci a)
a) Department of Medicine, University of Ottawa, Ottawa Hospital Research Institute, Ottawa, ON, Canada
b) Department of Anesthesiology, Critical Care, and Surgery, Duke University School of Medicine, Durham, NC, USA
c) Department of Medicine, McMaster University, Hamilton, ON, Canada
d) Department of Obstetrics and Gynecology and Perinatal Medicine, I.M. Sechenov First Moscow State Medical University, Moscow, Russia
e) Department of Pathology and Laboratory Medicine, Division of Hematology and Transfusion Medicine, The Ottawa Hospital, Ottawa, ON, Canada
Abstract
Introduction
Factor Xa inhibitor (FXaI)-associated bleeding events are common and associated with substantial morbidity. Systematic evaluation of widely available, effective, and affordable FXaI bleed management strategies is needed.
Materials and methods
We conducted a single-center retrospective cohort study of FXaI-treated patients presenting to a tertiary academic medical center from January 2018 to May 2019 who received 25–50 IU/kg 4F-PCC for either FXaI-associated major bleeding or urgent surgery. The primary outcome was hemostatic efficacy, and the safety outcome was the 30-day risk of thromboembolism.
Results
PCC was used to treat FXaI-associated bleeding in 83 cases (79.1 %) and was given before urgent surgery in 22 cases (20.9 %). Sixty-six patients were on apixaban, 38 were on rivaroxaban and one patient was on edoxaban. Intracranial hemorrhage (ICH) and gastrointestinal bleeding accounted for most bleeds (74.7 %). Median interval between last DOAC intake and presentation to triage was 9 h [IQR 5.3–14.8] and median PCC dosing was 40.0 IU/kg [IQR 28.5–46.6]. Forty-two patients (40.0 %) had pre-PCC FXaI levels drawn with median FXaI levels of 114.5 ng/mL [IQR 70.0–175.0]. Effective hemostasis occurred in 66.7 % [95%CI 55.4–76.3] of patients receiving PCC for bleeding and surgical hemostasis was rated as normal in 95.5 % (95%CI 76.5–100.0) for patients having urgent surgery. The 30-day risk of thromboembolism was 7.6 % [95%CI 3.7–14.5] and 22.9 % [95%CI 15.8–31.8] of patients died.
Conclusions
PCC for FXaI-associated bleeding was associated with hemostatic efficacy in two-thirds of patients and thromboembolic events were uncommon. PCC represents a promising treatment strategy for FXaI-associated bleeding.