Prehospital Lyophilized Plasma Transfusion for Trauma-Induced Coagulopathy in Patients at Risk for Hemorrhagic Shock: A Randomized Clinical Trial

Abstract

Importance: Blood transfusion is a mainstay of therapy for trauma-induced coagulopathy, but the optimal modalities for plasma transfusion in the prehospital setting remain to be defined.

Objective: To determine whether lyophilized plasma transfusion can reduce the incidence of trauma-induced coagulopathy compared with standard care consisting of normal saline infusion.

Design, setting, and participants: This randomized clinical trial was performed at multiple centers in France involving prehospital medical teams. Participants included 150 adults with trauma who were at risk for hemorrhagic shock and associated coagulopathy between April 1, 2016, and September 30, 2019, with a 28-day follow-up. Data were analyzed from November 1, 2019, to July 1, 2020.

Intervention: Patients were randomized in a 1:1 ratio to receive either plasma or standard care with normal saline infusion (control).

Main outcomes and measures: The primary outcome was the international normalized ratio (INR) on arrival at the hospital. Secondary outcomes included the need for massive transfusion and 30-day survival. As a safety outcome, prespecified adverse events included thrombosis, transfusion-related acute lung injury, and transfusion-associated circulatory overload.

Results: Among 150 randomized patients, 134 were included in the analysis (median age, 34 [IQR, 26-49] years; 110 men [82.1%]), with 68 in the plasma group and 66 in the control group. Median INR values were 1.21 (IQR, 1.12-1.49) in the plasma group and 1.20 (IQR, 1.10-1.39) in the control group (median difference, -0.01 [IQR, -0.09 to 0.08]; P = .88). The groups did not differ significantly in the need for massive transfusion (7 [10.3%] vs 4 [6.1%]; relative risk, 1.78 [95% CI, 0.42-8.68]; P = .37) or 30-day survival (hazard ratio for death, 1.07 [95% CI, 0.44-2.61]; P = .89). In the full intention-to-treat population (n = 150), the groups did not differ in the rates of any of the prespecified adverse events.

Conclusions and relevance: In this randomized clinical trial including severely injured patients at risk for hemorrhagic shock and associated coagulopathy, prehospital transfusion of lyophilized plasma was not associated with significant differences in INR values vs standard care with normal saline infusion. Nevertheless, these findings show that lyophilized plasma transfusion is a feasible and safe procedure for this patient population.

Trial registration: ClinicalTrials.gov Identifier: NCT02736812.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Jost reported receiving grants from the French Defence Central Health Service during the conduct of the study. Dr Arock reported receiving personal fees from Blueprint Medicines Corporation outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Flowchart of Trial Inclusion

The modified intention-to-treat population included all randomized patients, excluding those who were deemed ineligible after randomization. Patients who withdrew consent were not included in the analysis.

Figure 2.. Kaplan-Meier Estimates of Survival at 30 Days

A Cox proportional hazards regression model showed no difference in risk of death within 30 days after inclusion between the plasma and control groups (hazard ratio, 1.12 [95% CI, 0.48-2.64]; P = .79) or after adjusting for age and Injury Severity Score (hazard ratio, 1.07 [95% CI, 0.44-2.61]; P = .89). Tick marks indicate censored data. The time axis is represented on a logarithmic scale.