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Fixed Versus Variable Dosing of Prothrombin Complex Concentrate in Vitamin K Antagonist-Related Intracranial Hemorrhage: a Retrospective Analysis
Abdoellakhan RA, Miah IP, Khorsand N, et al. Neurocrit Care. 2017;26:64-9.
Study Question: How does fixed dose prothrombin complex concentrate (PCC) compare to variable dosing in reaching target International Normalized Ratio (INR)?
Study Description: In this single-center, retrospective study, the authors compared pre- and post-implementation of a fixed dose PCC protocol for adult patients presenting with vitamin K antagonist (VKA)-related intracranial hemorrhage (ICH). The study was conducted from January 2013 to August 2014. The variable dosing was based on the manufacturer recommendations by weight and INR; the fixed dose was 1000 IU factor IX, with an additional 500 IU administered if target INR was not reached. A single formulation of PCC was used (Cofact®), which is a four-factor PCC without activated factors or heparin. The primary outcome was achievement of the target INR of £1.5.
Results: Fifty-three patients met inclusion criteria and were evaluated (variable dose, n =25; fixed dose, n=28). There were no differences in baseline characteristics between groups. Patients in the variable dose (VD) group received a median dose of 1750 IU (IQR 1000-2500) compared to 1000 IU (IQR 1000-3000) in the fixed dose (FD) group (p=0.005). Patients in the VD group achieved the target INR after the initial dose more frequently (96% vs. 68%; p=0.01) and had less need for an additional dose (8% vs. 32%; p=0.04). The door-to-order and door-to-needle time did not differ between groups (p=0.370 and 0.42, respectively). No patients developed rebleeding, although two patients in the VD group developed thromboembolic events. There was no significant difference in degree of disability at discharge (measured by modified Rankin Scale [mRS]); duration of stay in the emergency department, intensive care unit, or hospital; or in-hospital mortality and mortality at 30 days, between the two groups.
Conclusion(s): Variable dosing of PCC achieved a target INR of ≤1.5 after the initial dose more often than a fixed dose regimen.
Perspective: This study showed that the variable dosing strategy was more likely to achieve target INR after an initial dose, though this did not lead to a difference in clinical outcomes, which is likely limited due to the retrospective design of this study and missing data. The fixed dose regimen also did not lead to a statistical difference in time to administration of PCC, though this may have been due to a small study size. Information regarding other blood products or factors was missing from this study and may affect the primary outcome. Additionally, no information was provided in regards to the time to attainment of the target INR. Future studies exploring fixed dose PCC should focus on determining the optimal fixed dose and the clinical relevance of meeting the target INR following an initial dose.