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Activated Prothrombin Complex Concentrate versus Plasma for Reversal of Warfarin-Associated Hemorrhage
Rowe AS, Mahbubani PS, Bucklin MH, et al. Pharmacotherapy. 2016; 36: 1132-1137.
Study Question: Is the use of activated four-factor aPCC safer and more effective than plasma for the reversal of warfarin-associated hemorrhage?
Study Description: This was a single-center, retrospective cohort of patients treated with either aPCC or plasma for warfarin-related hemorrhage. Data was collected between January 1, 2011 and July 1, 2013. Exclusion criteria were patients who received either aPCC or plasma for a different indication, or patients who had missing data points. There was no minimum pretreatment INR cutoff. The primary endpoint was the comparison of the posttreatment INR values between both groups. Secondary endpoints included INR reduction to <1.4, <1.2, thromboembolic events, transfusion/infusion reactions, and mortality. Per hospital guidelines, aPCC dosing was 500 units if the initial INR was <5 and 1000 units if the initial INR was ³5. The recommended dose of plasma was 5-20 mL/kg. In addition, all patients should have received Vitamin K 10 mg IV.
Results: Of the 538 patients evaluated, 128 received aPCC, and 148 received plasma. Patients in the aPCC group were more likely to receive vitamin K (70.9% vs. 50.7%, p = 0.001) and had a higher pretreatment INR (2.7 vs 2.3, p = 0.025). Patients in the aPCC group achieved a lower posttreatment INR (1.1 vs 1.6, p < 0.05) and were more likely to achieve an INR < 1.4 (75.8% vs. 43.9%, p <0.05; OR 4.3, 95% CI 2.6-7.3). There was no difference in transfusion/infusion reactions or mortality between groups.
Conclusion(s): Patients treated with aPCC compared to plasma achieved lower posttreatment INR values, greater INR change, and a greater likelihood of obtaining an INR <1.4 and <1.2 without an increased risk of thromboembolic events.
Perspective: PCCs have been shown in previous studies to provide a more rapid decrease in INR compared to plasma. This study demonstrated a greater INR reduction in the aPCC group compared to plasma with no difference in adverse events or mortality. The wide range in plasma dosage may confound the impact of this treatment along with the relatively low vitamin K administration rate. In critically ill patients with a warfarin-associated major bleed needing urgent INR reversal, PCCs, including aPCC are rapidly becoming the preferred therapy over plasma.