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Activated Prothrombin Complex Concentrate Versus 4-Factor Prothrombin Complex Concentrate for Vitamin K-Antagonist Reversal
Rowe AS, Dietrich SK, Phillips JW, Foster KE, Canter JR. Crit Care Med. 2018; 46: 943-948.
Study Question: How does low, fixed-dose activated prothrombin complex concentrate (aPCC) compare to standard-dose four factor prothrombin complex concentrate (4PCC) for international normalized ratio (INR) normalization and thrombotic complications?
Study Description: This retrospective, multicenter cohort study identified adult patients that received either aPCC or 4PCC for the treatment of warfarin-associated hemorrhage. Pregnant patients, those with a baseline INR ˂ 2, and those requiring massive transfusion protocols or plasma infusions were excluded. The primary endpoint was achievement of post-treatment INR ˂ 1.4 within 24 hours. Secondary endpoints included achievement of post-treatment INR ˂ 1.2, thromboembolic complications and cost. Patients that received aPCC (FEIBA) were dosed using a fixed-dose protocol: 500 units for an INR ˂ 5 and 1000 units for an INR ≥ 5. Those receiving 4PCC (Kcentra) were dosed according to package insert weight-based dosing.
Results: A total of 158 patients were included; 118 received aPCC and 40 received 4PCC. Patients in the aPCC group had a lower pre-treatment INR (2.7 vs. 3.5; p = 0.0164) and presented more often with intracranial hemorrhage (78.8% vs. 45% of patients; p < 0.0001). There was no significant difference in INR normalization to less than 1.4 within 24 hours between the groups (aPCC 77.1% vs. 4PCC 62.5%; p = 0.075). A logistic regression was performed to control for pre-treatment INR and receipt of the correct PCC dose. After adjusting, patients who received aPCC were 3.23 times more likely to achieve post-treatment INRs ˂ 1.2 compared to 4PCC (95% CI 1.344-7.813; p = 0.0009). No significant difference in thrombotic complications were noted. The median cost of aPCC treatment was $825, and 4PCC was $5,735.80.
Conclusion(s): Low, fixed-dose aPCC was found to be as effective as standard-dose 4PCC for normalization of INR in patients with warfarin-associated hemorrhage.
Perspective: With a primary endpoint of 24-hour INR normalization, it may be difficult to apply these results in clinical practice. In acute, life-threatening bleeding episodes, reversal would need to occur within minutes. Further, a large proportion of patients in both groups received vitamin K, which would also be expected to contribute to INR normalization within the 24-hour study timeframe.