Background: While anticoagulants are the core treatment plan for preventing strokes in patients with atrial fibrillation and managing patients with thromboembolic disease, there is a dichotomy of efficacy and harm with their use. Rapid inpatient reversal protocols are important for patient safety. Four factor prothrombin complex concentrate (4FPCC) is approved for reversal of warfarin-induced coagulopathy. Recommended dosing is dependent on pre-treatment INR and weight, information that is not readily available in emergency situations. This study aimed to determine the efficacy of two different protocolized non-weight based doses of 4FPCC.
Methods: We analyzed a retrospective cohort of patients taking warfarin who received 4FPCC for life-threatening bleeding or reversal for urgent procedure. Patients treated between August 2014 and July 2015 at a Level 1 Trauma Center and a Tertiary Care Center were identified using blood bank records. In our institutional protocol, patients received an initial dose of 1500+/-200 IU 4FPCC (1500PCC group) for intracranial bleeding and 1000+/-200 IU 4FPCC (1000PCC group) for extracranial bleeding. Statistical analysis was performed using R (R Foundation for Statistical Computing, Vienna, Austria) after the completion of data collection. Categorical variables were compared using the x^2 test and continuous variables were compared using Mann-Whitney U test for univariate analysis. Multivariate analysis was performed using multiple linear regression.
Results: 219 patients met our inclusion criteria. In the 1500PCC group (n=75) compared to the 1000PCC group (n=144), both the baseline mean [±SD] INR (3.3 [±2.1] vs. 5.0 [±3.8], p<0.001) and the post-treatment INR (1.4 [±0.2] vs. 1.8 [±0.5] p<0.001) were significantly lower. More patients achieved an INR < 2.0 in the 1500PCC than the 1000PCC group (95% vs 74%, p<0.001). Similarly, more patients achieved an INR < 1.5 in the 1500PCC than the 1000PCC group (76% vs. 28.5%, p<0.0001). After adjusting for the baseline INR, there is a 0.27 IU average decrease in post 4FPCC INR going from the low to the high dose group. The fixed 1500IU dose in the 1500PCC group was significantly lower than the dose recommended by the FDA (1628 ± 37 vs 2390 ± 1082, p < 0.0001), resulting in a mean cost savings of $1075 ± 1521 per patient. There was no significant difference between the groups in 7 day post treatment thrombotic events or all-cause mortality.
Conclusions: Using a protocol prescribing two fixed doses of 4FPCC, a 1500IU dose was more effective than a 1000IU dose in achieving a post-treatment INR less than 2 and 1.5. The effectiveness of a fixed 1500IU dose can potentially allow for rapid one-time PCC dosing in most patients requiring warfarin reversal that avoids delays in acquiring pretreatment INR and weight and results in significant cost savings.