In this episode, I’ll discuss a recent retrospective review that has implications for fixed dose 4FPCC.
Fixed dosing of 4-factor prothrombin complex concentrate has several potential advantages, including faster availability of the product, the potential elimination of the need to wait for a pretreatment INR result, and reduced cost. Typical exclusions to fixed dosing protocols are patients at extremes of body weight.
A recent retrospective analysis on the impact of timing and dosing of four-factor prothrombin complex concentrate administration on outcomes in warfarin-associated intracranial hemorrhage raises potential concerns on fixed dosing of 4FPCC for this indication.
The study was performed with the goal of identifying an ideal timeframe for the administration of 4FPCC that resulted in the best reduction of hematoma expansion or death due to neurologic injury. No such timeframe was identified when patients were analyzed and compared by their initial Glasgow Coma Scale (GCS) score.
However, the study did note that if failure was defined as the initial 4FPCC dose not achieving a post-treatment INR of 1.3 or less, fixed dosing had a statistically significant higher failure rate of 65% compared with just 24.2% failure with weight-based dosing. Despite this, the authors state they did not observe any difference in primary outcome between weight-based or fixed-dose 4F-PCC. There were only 94 patients in the study however, so a type II error cannot be excluded. The results could also be explained by the amount of time that elapsed until the 2nd INR was drawn. The mean time to 2nd INR draw was just under 4 hours and the standard deviation was just over 4 hours, resulting in 95% of the repeat INRs being drawn within 13.4 hours.
The authors acknowledge these limitations and stop short of recommending against the use of fixed dosing of 4FPCC for warfarin related ICH, however they do suggest that further research be done to identify the ideal timing and dosing strategy for this indication.
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