Objective
The objective of this systematic review and meta-analysis is to evaluate the efficacy, safety, time to international normalized ratio (INR) reversal, and total volume of four-factor prothrombin complex concentrate (4-PCC) administered using fixed-dose versus weight-based dosing strategies in patients requiring urgent warfarin reversal, with specific focus on clinical outcomes of hemostatic efficacy, thromboembolic events, and mortality rates.
Methods
A comprehensive systematic review was conducted using the PubMed, Embase, and Cochrane databases from inception through October 2023. We searched for randomized clinical trials or observational studies that compared efficacy or safety outcomes of fixed versus variable 4-PCC dose in adult patients.
Results
In the 14 included studies, the overall use of fixed-dose 4-PCC was associated with a lower likelihood of reaching the INR goal (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.80–0.89) compared to the variable-dose group. In addition, a significantly larger proportion of patients (169 of 651, 26%) required an additional dose of 4-PCC. The rates of mortality (RR, 0.85; 95% CI, 0.70–1.03) and thromboembolic events (RR, 1.27; 95% CI, 0.65–2.45) were similar between the two treatment groups.
Conclusion
This systematic review and meta-analysis showed that variable dosing of 4-PCC more successfully achieves the target INR for warfarin reversal compared to fixed dosing. However, the dosing strategies have similar mortality and thromboembolic rates. While fixed dosing offers a simpler approach, it may require additional administration. Future studies should focus on optimizing dosing strategies to balance efficacy, safety, and practicality in various clinical scenarios

Objective
Four-factor prothrombin complex concentrate (4F-PCC) was approved by the US Food and Drug Administration in 2013 for management of severely bleeding patients on warfarin therapy. We describe use of 4F-PCC at a large, suburban academic center.
Methods
We retrospectively reviewed all patients receiving 4F-PCC from its introduction through 2016 at a large level 1 trauma center. Clinical and demographic data were obtained, including indications for anticoagulation and antiplatelet agents, comorbidities, concomitant medications, etiology and site of bleeding, as well as disposition, length of stay, mortality, and thrombotic events.
Results
One hundred eighty-four patients received 4F-PCC. Mean age was 72 years; 40.8% were female. Indications for 4F-PCC administration included: active bleeding (74%), reversal prior to a procedure (14%), and elevated international normalized ratio (12%). Warfarin was the most common concomitant medication (71.1%). Most patients were receiving anticoagulation for atrial fibrillation (63%). Concomitant treatments for bleeding included vitamin K (58.2%), packed red blood cells (50%), fresh frozen plasma (38%), and platelets (26.1%), amongst others. Median length of hospital stay was 8.4 days. Nine patients (4.9%) developed thrombosis within 90 days of 4F-PCC. Mortality was 24.5%, with notably higher rates amongst those who received 4F-PCC for off-label indications (19.1% on-label mortality vs. 37.7% off-label mortality on chi-square analysis, P=0.01).
Conclusion
This study demonstrates that 4F-PCC is being utilized for indications other than the reversal of warfarin-induced coagulopathy. Further investigation is warranted to determine the efficacy and safety of 4F-PCC for these potential indications.