Propensity score adjusted comparison of three-factor versus four-factor prothrombin complex concentrate for emergent warfarin reversal: a retrospective cohort study

Abstract

Background Prothrombin Complex Concentrates (PCC) are prescribed for emergent warfarin reversal (EWR). The comparative effectiveness and safety among PCC products are not fully understood. Methods Patients in an academic level one trauma center who received PCC3 or PCC4 for EWR were identified. Patient characteristics, PCC dose and time of dose, pre- and post-INR and time of measurement, fresh frozen plasma and vitamin K doses, and patient outcomes were collected. Patients whose pre-PCC International Normalized Ratio (INR) was > 6 h before PCC dose or the pre-post PCC INR was > 12 h were excluded. The primary outcome was achieving an INR ≤ 1.5 post PCC. Secondary outcomes were the change in INR over time, post PCC INR, thromboembolic events (TE), and death during hospital stay. Logistic regression modelled the primary outcome with and without a propensity score adjustment accounting for age, sex, actual body weight, dose, initial INR value, and time between INR measurements. Data are reported as median (IQR) or n (%) with p < 0.05 considered significant. Results Eighty patients were included (PCC3 = 57, PCC4 = 23). 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 result remained true after adjusting for possible confounders (AOR = 10.7, 95% CI: 2.17–51.24, p < 0.001). The post-PCC INR was lower in the PCC4 group (1.3 (1.3–1.5) vs. 1.7 (1.5–2.0)). The INR change was greater for PCC4 (2.3 (1.3–3.3) vs. 1.1 (0.6–2.0), p = 0.003). Death during hospital stay (p = 0.52) and TE (p = 1.00) were not significantly different. Conclusions PCC4 was associated with a higher achievement of goal INR than PCC3. This relationship was observed in the unadjusted and propensity score adjusted results.

Comparison of 3-Factor Versus 4-Factor Prothrombin Complex Concentrate for Emergent Warfarin Reversal: A Systematic Review and Meta-Analysis

“…Of the remainder, 15 were selected based on inclusion and exclusion criteria for the qualitative synthesis (systematic review). Three of these 15 were excluded [21,29,34], leaving 12 included [20,[22][23][24][25][26][27][28][30][31][32][33] for the quantitative synthesis (meta-analysis). A PRISMA ow diagram of study inclusion is shown in Fig.…”

“…Reversal to INR goal was limited to the warfarin group in this study. Another study was primarily concerned with non-warfarin-related coagulopathy; however, the results from patients on warfarin reversed with PCCs were still extracted [32].…”

“…Nine journal articles reported TE outcomes included in the meta-analysis [20,22,24,25,27,28,[31][32][33]. There were 27 of 478 patients who had TE in the PCC4 group compared to 20 of 559 patients in the PCC3 group.…”

“…The rank correlation and regression test did not indicate funnel plot asymmetry (p = 0.76 and p = 0.59, respectively). Two studies reported no events in either treatment group [22,32]. Removing them from the analysis had no major impact on the interpretation of the results (OR = 1.61, 95% CI: 0.85-3.08, p = 0.15).…”

“…One systematic review without meta-analysis compared studies investigating PCC3 or PCC4 from various institutions [19]. Since its publication, several direct comparisons have been published as retrospective and observational studies [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34].This systematic review and meta-analysis of studies directly compares PCC3 to PCC4 in adult patients needing warfarin reversal for bleeding, surgical intervention, or trauma in patients taking warfarin before their hospital admission.…”