Among patients with trauma at risk of massive transfusion, early administration of 4-factor prothrombin complex concentrate (4F-PCC) did not lead to a significant reduction of 24-hour blood product consumption but was associated with a higher frequency of thromboembolic events, according to research published in JAMA.

Researchers conducted a double-blind, randomized, placebo-controlled superiority trial to investigate the efficacy and safety of 4F-PCC administration in consecutive patients with trauma at risk of massive transfusion ( Identifier: NCT03218722). The study took place at 12 French designated level I trauma centers between December 29, 2017, and August 31, 2021.

A total of 324 adult patients (median age, 39 years; interquartile range [IQR], 27-56; 73% men and 27% women) were included in the final analysis, where 164 received intravenous administration of 1 mL/kg of 4F-PCC (25 IU of factor IX/kg) and 160 received placebo, 1 mL/kg of saline solution. All patients were treated according to European traumatic hemorrhage guidelines and received early ratio-based transfusion.

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The primary outcome was 24-hour all blood product consumption and key secondary outcomes included arterial or venous thromboembolic events.

The study found no statistically or clinically significant difference in median total 24-hour blood product consumption between the 4F-PCC and placebo groups (12 [IQR, 5-19] U vs 11 [IQR, 6-19] U, respectively; absolute difference, 0.2 U; 95% CI, -2.99 to 3.33; P =.72).

The researchers found that more patients in the 4F-PCC group than in the placebo group presented with at least 1 thromboembolic event through day 28 (35% vs 24%, respectively; absolute difference, 11%; 95% CI, 1-21; relative risk, 1.48; 95% CI, 1.04-2.10; P =.03).

“The findings do not support systematic 4F-PCC use in patients with trauma at risk of massive transfusion,” the researchers concluded in their report.

Limitations of the study included administration of 4F-PCC in combination with fresh frozen plasma (FFP) without prior viscoelastic testing, use of 24-hour blood product use as a surrogate for a patient-centered outcome. There was also a longer delay to FFP administration in the placebo group despite randomization as well as potential influence of the intervention on the definition of the “massive transfusion” subgroup, including potential differences in the composition of commercially available 4F-PCC and the one used in the study.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. 


Bouzat P, Charbit J, Abback PS, et al. Efficacy and safety of early administration of 4-factor prothrombin complex concentrate in patients with trauma at risk of massive transfusion: The PROCOAG randomized clinical trial. JAMA. Published online March 21, 2023. doi:10.1001/jama.2023.4080