In this episode, I’ll discuss uisng fixed-dose PCC for warfarin reversal.
A recent systematic review and meta-analysis published in Critical Care Medicine has attempted to synthesize the data available on fixed vs variable dosing of 4-factor prothrombin complex concentrate for warfarin reversal in hopes to clarify the optimal dosing strategy for this indication.
The analysis included 3 randomized trials and 16 cohort studies. Just over 300 patients were represented in the randomized trials and just over 1900 patients were represented in the cohort studies. Bleeding from extracranial sites was the reason for reversal in a majority of patients in the combined study population.
The authors found a fixed-dose strategy likely results in increased clinical hemostasis compared with a variable-dose regimen with an odds ratio of 1.7 and a confidence interval that indicates moderate certainty. This data was drawn only from the cohort studies as it was not measured in the randomized trials.
For the goal of achieving an INR below 1.5, fixed dosing underperformed variable dosing with an odds ratio of 0.6 from the cohort studies and 0.3 from the randomized trials with moderate and high certainty, respectively.
When looking at mortality, fixed dosing was associated with lower mortality with an odds ratio of 0.8 from the cohort studies and 0.6 from the randomized trials both with a high degree of certainty.
Likewise when looking at thromboembolic events fixed dosing was associated with lower risk with an odds ratio of 0.5 from the cohort studies and 0.7 from the randomized trials with high and moderate certainty, respectively.
The authors also performed extensive pre-planned subgroup analyses, which they have detailed in tables 6 through 10 of their supplemental material.
Notable subgroup findings include:
– A progressive increase in efficacy when the fixed dose given was increased
– Intracranial hemorrhage had high mortality and there were few significant differences between strategies in this group
– When exact doses were analyzed, the 2000 unit fixed dose group performed best.
The authors concluded:
The findings of this meta-analysis indicate that a fixed-dose regimen of 4-PCC may offer advantages in terms of cost-effectiveness, administration time, efficacy, and safety.
The authors make a suggestion that if the fixed dose of 2000 units is chosen for an institutional policy, that subgroup data could be used to justify an additional supplemental dose for patients weighing at least 80 kg, presenting with ICH, or an INR greater than 4. In this scenario, the additional dose would be enough to catch the patient up to the usual variable dose recommendation, but the patient would still gain the benefits of receiving the first 2000 units without delay.
To access my free download area with 20 different resources to help you in your practice, go to pharmacyjoe.com/free.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.
Leave a Reply