Prothrombin complex concentrate for direct factor Xa inhibitor-associated bleeding or before urgent surgery.

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.

Effect of PCC on Thrombin Generation among Patients on Factor Xa Inhibitors with Major Bleeding or Needing Urgent Surgery (GAUGE): Design and Rationale.

Background Direct factor Xa inhibitors (FXaIs) account for most oral anticoagulant use and FXaI-associated bleeding events are common. Clinicians have variable national and regional access to specific FXaI reversal agents such as andexanet alfa. Many centers have adopted the use of prothrombin complex concentrates (PCCs) as hemostatic therapy for FXaI-associated major bleeding events. PCC does not impact circulating FXaI levels and its mechanism of action to achieve hemostasis in FXaI-associated bleeding is uncertain. While PCC increases quantitative thrombin generation assay (TGA) parameters, it does not correct FXaI-altered thrombin generation kinetics, nor does it normalize thrombin generation. Clinical data supporting the use of PCC are based on cohort studies reporting clinical hemostatic efficacy, which is difficult to measure. The benefits of PCC for FXaI-associated bleeding beyond supportive care are uncertain. Objective GAUGE is a prospective observational study designed to measure the effects of four-factor PCC administration (Octaplex) on TGA parameters among patients with FXaI-associated bleeding or needing urgent surgery. Methods Laboratory outcomes will include the mean paired change in TGA parameters from pre- to post-PCC administration and the proportion of participants whose post-PCC TGA values fall within a defined reference range. Clinical outcomes will include hemostatic efficacy, thromboembolic complications, and all-cause death at 30 days post-PCC. Conclusion Development of a viable and universally accessible FXaI bleed management strategy is crucial. GAUGE will provide in vivo data on the effects of PCC among patients with FXaI-associated bleeding.

Activated prothrombin complex concentrates for direct oral anticoagulant-associated bleeding or urgent surgery: Hemostatic and thrombotic outcomes.

INTRODUCTION: Studies evaluating the use of activated prothrombin complex concentrates (aPCCs) for DOAC-associated bleeding are sparse. MATERIALS AND METHODS: We conducted a retrospective study of patients receiving aPCC for DOAC-associated bleeding or for pre-operative optimization of hemostasis prior to urgent surgery. The primary efficacy outcome was hemostatic efficacy, the primary safety outcome was the 30-day thromboembolic complication rate. RESULTS: Eighty-two patients were included in the analysis; 14 patients on dabigatran, 39 patients on rivaroxaban and 29 patients on apixaban. Fifty-four patients received aPCC for major bleeding and 28 patients prior to urgent surgery. Mean aPCC dosing was 2974 IU (SD ± 857 IU). Hemostasis was deemed effective by ISTH criteria in 50% of cases and "Good" or "Moderate" by Sarode criteria in 45.2% and 14.3% of cases, respectively. Surgical hemostasis was rated as "Normal" in 84% of cases pre-operative administration. Median pre-aPCC INR was 1.6 (IQR 0.5) and median post-aPCC INR was 1.2 (IQR 0.2) (p < 0.00001). Median pre-aPCC aPTT was 36 s (IQR 12.8), median post-aPCC aPTT was 29 s (IQR 9.8) (p = 0.0001). The 30-day thromboembolic event rate was 6.1%. CONCLUSION: Further study is needed to characterize the hemostatic effects and thromboembolic risk of aPCC among patients with DOAC-associated bleeding or for attempted normalization of hemostasis prior to urgent surgery.