Fixed- versus variable-dose prothrombin complex concentrate protocol for vitamin K antagonist reversal

Abstract

Fixed-dose prothrombin complex concentrates (PCCs) for the reversal of vitamin K antagonists may decrease the incidence of thromboembolic events, treatment costs, and treatment delays. However, the ideal fixed dose is unknown, with some studies showing inadequate reversal with suboptimal dosing or in patients with a higher international normalized ratio (INR) or weight. This indicates a need for a modified fixed-dose strategy that considers weight and INR. This study was a retrospective chart review comparing efficacy and safety outcomes of the standard variable-dose protocol versus a fixed-dose protocol. The primary outcome was the proportion of patients who achieved INR reversal. Of the total of 113 patients reviewed, INR reversal to < 1.5 was achieved in 23 patients (46%) in the variable-dose group versus 27 patients (43%) in the fixed-dose group (P = 0.83). Of the 27 patients with ICH, INR reversal to ≤ 1.3 was achieved in five patients (71%) in the variable dose group versus ten patients (50%) in the fixed-dose group (P = 0.41). The rate of INR reversal did not differ significantly between groups, but the fixed-dose group used less PCCs and had lower treatment costs.

Appendices

Appendix A: Data

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Table 1 Baseline characteristics

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Table 2 INR reversal

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Table 3 Characteristics of 4FPCCs

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Table 4 Adverse events

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Table 5 Subgroup analysis based on weight and INR

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Table 6 Subgroup analysis based on other reversal products given

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Table 7 Subgroup analysis based on patients who were dosed appropriately per protocol

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Table 8 Expected versus actual 4FPCC dose given in fixed dose protocol

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Appendix B: Study Protocols

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Table 9 BSLMC urgent or emergent VKA reversal protocol

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Table 10 Package insert dosage recommendations

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