Efficacy and Safety of Early Administration of 4-Factor Prothrombin Complex Concentrate in Patients With Trauma at Risk of Massive Transfusion
Authors: Bouzat Pierre , Charbit Jonathan , Abback Paer-Selim , Huet-Garrigue Delphine , Delhaye Nathalie , Leone Marc , Marcotte Guillaume , David Jean-Stéphane , Levrat Albrice , Asehnoune Karim , Pottecher Julien , Duranteau Jacques , Courvalin Elie , Adolle Anais , Sourd Dimitri , Bosson Jean-Luc , Riou Bruno , Gauss Tobias , Payen Jean-François ,   PROCOAG Study Group, Greze Jules , Banco Pierluigi , Berger Karine , Druge Stéphanie , Dupuis Martin , Janin Laure , Machuron Caroline , Thomas Marine , Schilte Clotilde , Hamad Emmanuelle , Zieleskiewicz Laurent , Duclos Gary , Arbelot Charlotte , Bezulier Karine , Jeantrelle Caroline , Raux Mathieu , Glasman Pauline , Harrois Anatole , Tarazona Virginie , Lambert Aline , Vassal Olivia , Li Anne , Grillot Nicolas , Henry Loïs , Blonde Elise , Bijok Benjamin , Rohn Aurélien , Bellet Julie , Lallemant Florence , Bruneau Nathalie , Ducam Christine , Dagod Geoffrey , Deras Pauline , Capdevila Xavier , Szczot Magdalena , Meyer Alain , Hecketsweiler Stéphane , Escudier Etienne , Muller Michel , Gray Samuel , Farines Magalie , Lebouc Marie , DEBORD-PEDET Sophie 
Published: March 2023

Importance

Optimal transfusion strategies in traumatic hemorrhage are unknown. Reports suggest a beneficial effect of 4-factor prothrombin complex concentrate (4F-PCC) on blood product consumption.

Objective

To investigate the efficacy and safety of 4F-PCC administration in patients at risk of massive transfusion.

Design, Setting, and Participants

Double-blind, randomized, placebo-controlled superiority trial in 12 French designated level I trauma centers from December 29, 2017, to August 31, 2021, involving consecutive patients with trauma at risk of massive transfusion. Follow-up was completed on August 31, 2021.

Interventions

Intravenous administration of 1 mL/kg of 4F-PCC (25 IU of factor IX/kg) vs 1 mL/kg of saline solution (placebo). Patients, investigators, and data analysts were blinded to treatment assignment. All patients received early ratio-based transfusion (packed red blood cells:fresh frozen plasma ratio of 1:1 to 2:1) and were treated according to European traumatic hemorrhage guidelines.

Main Outcomes and Measures

The primary outcome was 24-hour all blood product consumption (efficacy); arterial or venous thromboembolic events were a secondary outcome (safety).

Results

Of 4313 patients with the highest trauma level activation, 350 were eligible for emergency inclusion, 327 were randomized, and 324 were analyzed (164 in the 4F-PCC group and 160 in the placebo group). The median (IQR) age of participants was 39 (27-56) years, Injury Severity Score was 36 (26-50 [major trauma]), and admission blood lactate level was 4.6 (2.8-7.4) mmol/L; prehospital arterial systolic blood pressure was less than 90 mm Hg in 179 of 324 patients (59%), 233 patients (73%) were men, and 226 (69%) required expedient hemorrhage control. There was no statistically or clinically significant between-group difference in median (IQR) total 24-hour blood product consumption (12 [5-19] U in the 4F-PCC group vs 11 [6-19] U in the placebo group; absolute difference, 0.2 U [95% CI, −2.99 to 3.33]; P = .72). In the 4F-PCC group, 56 patients (35%) presented with at least 1 thromboembolic event vs 37 patients (24%) in the placebo group (absolute difference, 11% [95% CI, 1%-21%]; relative risk, 1.48 [95% CI, 1.04-2.10]; P = .03).

Conclusions and Relevance

Among patients with trauma at risk of massive transfusion, there was no significant reduction of 24-hour blood product consumption after administration of 4F-PCC, but thromboembolic events were more common. These findings do not support systematic use of 4F-PCC in patients at risk of massive transfusion.

Trial Registration

ClinicalTrials.gov Identifier: NCT03218722