Prothrombin complex concentrate for oral factor Xa inhibitor reversal prior to urgent invasive procedures

BACKGROUND: Oral factor Xa (FXa) inhibitors are anticoagulants with no approved reversal agent for use before urgent invasive procedures. Four-factor prothrombin complex concentrate (4F-PCC) is used off-label for this despite limited evidence regarding its effectiveness and safety. AIMS: To determine the efficacy of 4F-PCC prior to urgent invasive procedures in FXa inhibitor-treated patients. Secondary aims were hemoglobin levels and transfusion requirements within 48 h following the procedure, to determine the effect of treatment on anti-FXa levels and to document thromboembolic events and mortality at 30 days. METHODS: We conducted a prospective, single-center observational study of consecutive adults receiving 4F-PCC for reversal of oral FXa inhibitors before urgent invasive procedures with moderate-to-high bleeding risk. RESULTS: Fifty-nine were included in the analysis (median age 78 years). Apixaban was the most frequently used anticoagulant (83.1%). 74.6% underwent urgent surgical procedures and 25.4% underwent other invasive procedures. The median 4F-PCC dose was 2000 units. The primary endpoint of normal or mildly abnormal hemostasis was achieved in 89.8% of patients (84.7% normal, 5.1% mildly abnormal). About 10.2% had moderately abnormal hemostasis; no patients had severe hemostatic failure. Median hemoglobin decline was 1.5 g/dL, with 8.5% of patients requiring red blood cell transfusion. In 17 patients with paired measurements, median decrease in anti-FXa activity was 42%. Thromboembolic events occurred in 5.1%, and 30-day mortality was 10.2%. CONCLUSIONS: Thromboembolic events were infrequent. These data support the use of 4F-PCC for reversal of FXa inhibitors prior to urgent invasive procedures with a moderate or high bleeding risk.