Propensity Score Adjusted Comparison of Prothrombin Complex Concentrates (PCC) for Warfarin Reversal

Introduction/Hypothesis: Three factor PCC (PCC3) and four factor PCC (PCC4) are prescribed for emergent warfarin reversal (EWR). While current guidelines recommend PCC4, few direct comparisons with PCC3 exist. This study describes and characterizes the differences between PCC4 and PCC3 in patients who required EWR. Methods: Patients who received PCC3 or PCC4 for EWR were retrospectively identified and data (patient characteristics, PCC dose and time of dose, pre and post INR and time of measurement, FFP and vitamin K doses, and patient outcomes) were collected. Patients whose pre-PCC INR was > 6 hours before PCC dose or the pre-post PCC INR was >12 hours were excluded. The primary outcome was achieving an INR ≤ 1.5 post PCC. Secondary outcomes were the change in INR over time, post INR, thromboembolic events (TE), and survival between the PCC3 and PCC4 groups. The primary outcome was modeled using logistic regression with and without a propensity score adjustment accounting for actual body weight, PCC dose, initial INR value, and time from the first and second INR measurement. Data are reported as median (IQR) or n (%) with p<0.05 considered significant. Results: Eighty patients were included (PCC3 = 57, PCC4 = 23). Baseline INR was similar (p=0.10). Dose (U/kg) was greater for PCC4 patients (29.3 (25.9-37.3) vs. 21.5 (20.4-25.9), p<0.001). However, the U/kg:INR ratio was not different ( PCC4: 8.2 (7.0-10.2) vs PCC3: 7.9 (5.6-10.5), p=0.3). The crude pre-post INR change was greater for PCC4 (2.3 (1.3-3.3) vs. 1.1 (0.6-2.0), p = 0.003)). More PCC4 patients achieved goal INR (87.0% vs. 31.6%, odds ratio (OR) =14.4, 95% CI: 3.80-54.93, p<0.001). This held after adjustment (Adjusted OR = 12.7, 95% CI: 2.57-62.42, p<0.001). The post-INR was lower in the PCC4 group (1.3 (1.3-1.5) vs. 1.7 (1.5-2.0), p < 0.001). Minutes from PCC dose to post-PCC INR differed (PCC3: 93 (46.0-228.0) vs. PCC4: 226 (156.5-368.5), p<0.001), but when stratified by time from PCC dose to post-INR, this didn't influence the goal INR achievement results favoring PCC4. Survival (p=0.52) and TE (p=1.00) were similar. Conclusions: PCC4 was associated with a higher achievement of goal INR than PCC3. This relationship was observed in the unadjusted, propensity score adjusted, and time stratified results.