Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial

Abstract

Importance: Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials.

Objective: To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio.

Design, setting, and participants: Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013.

Interventions: Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled).

Main outcomes and measures: Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status.

Results: No significant differences were detected in mortality at 24 hours (12.7% in 1:1:1 group vs 17.0% in 1:1:2 group; difference, -4.2% [95% CI, -9.6% to 1.1%]; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, -3.7% [95% CI, -10.2% to 2.7%]; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6% in 1:1:2 group; difference, -5.4% [95% CI, -10.4% to -0.5%]; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P < .001) and platelets (12 U vs 6 U, P < .001) and similar amounts of red blood cells (9 U) over the first 24 hours, no differences between the 2 groups were found for the 23 prespecified complications, including acute respiratory distress syndrome, multiple organ failure, venous thromboembolism, sepsis, and transfusion-related complications.

Conclusions and relevance: Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups.

Trial registration: clinicaltrials.gov Identifier: NCT01545232.

Conflict of interest statement

Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Rizoli reported receiving grant funding from TEM International and CSL Behring. Dr Stein reported serving as an advisor for Decisio Health for which she receives travel reimbursement. No other disclosures were reported.

Figures

Figure 1. Flow of Patients in the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) Trial

CPR indicates cardiopulmonary resuscitation; ED, emergency department; RBC, red blood cell. aIncluded patients with the following: 6 known pregnancies, 5 with physicians who refused to randomize, 4 with known do-not-resuscitate order prior to randomization, 3 with burns covering more than 20% of total body surface area, 1 with a documented inhalation injury, 1 who opted out upon arrival to the ED, 1 unknown reason. bThe vital statistic data were obtained for patients who withdrew consent when available. Patients who withdrew consent at 24 hours are included in the count of those who withdrew at 30 days.

Figure 2. Kaplan-Meier Failure Curves for Mortality at 24 Hours and 30 Days

The colored areas indicate 95% confidence bands, which were calculated using the Hall-Wellner method. The Hall-Wellner bands extend to the last event (death) in each group. For 24-hour mortality, the Cox proportional hazards regression model, adjusted for site as a random effect, produced a hazard ratio (HR) of 0.72 (95% CI, 0.49–1.07). There were no patients lost to follow-up during the first 24 hours from randomization. For 30-day mortality, the Cox proportional hazards regression model, adjusted for site as a random effect, produced an HR of 0.83 (95% CI, 0.61–1.12). Between 24 hours and 30 days, 4 patients were lost to follow-up and were censored when they withdrew consent or were last known to be alive (3 in the 1:1:1 group and 1 in the 1:1:2 group).

Figure 3. Distribution of Cumulative Blood Product Ratios Within Period up to 24 Hours After Admission

Prerandomization blood products include those given prior to hospital arrival. Patients who received no red blood cells (RBCs) within an interval were excluded because RBCs are in the ratio denominator. The lower and upper edges of the boxes are the 25th and 75th percentiles, the whiskers extend to ±1.5 × the interquartile range, and the points outside are the outliers. The thick line inside the box represents the median and the circle is the mean.

Figure 4. Distribution of Blood Product Amounts Within Period up to 24 Hours After Admission

Prerandomization blood products include those given prior to hospital arrival. The lower and upper edges of the boxes are the 25th and 75th percentiles, the whiskers extend to ±1.5 × the interquartile range, and the points outside are the outliers. The thick line inside the box represents the median and the circle is the mean. Five or 6 U pools of whole blood–derived platelets were considered equivalent to 1 U of apheresis platelets (eg, an adult dose of platelets).