Injury is the leading cause of death in the United States in the 1 to 44 year old age group and the 3rd leading cause of death overall. In patients reaching the hospital with trauma, massive hemorrhage is a major cause of mortality. Damage control resuscitation (DCR) is a concept first put forward by the US Department of Defense in 2004 but has been widely adopted for civilian trauma as well. One of the critical components of DCR is resuscitation with blood products. While it makes sense to replace whole blood loss in trauma with the components constituting whole blood (plasma, platelets and PRBCs), there are no large randomized controlled trials looking at mortality as the primary outcome. The PROPPR study sought to fill this void.
What is the optimal ratio for blood product transfusion in patients with major bleeding after severe trauma; 1:1:1 or 1:1:2 (plasma:platelets:PRBCs)?
All persons > 15 years old with an injury severe enough to lead to the highest local trauma activation at 12 level 1 trauma centers in North America.
Blood product transfusion ratio of 1:1:1
Blood product transfusion ratio of 1:1:2
Primary: 24-hour and 30-day all-cause mortality
Secondary: Death from exsanguination at 24-hours
Multicenter, randomized clinical trial.
Expected death within 1 hour of admission, 3 units of PRBC transfusion prior to randomization, age < 15 or < 50 kg (see box 1 of study for all exclusion criteria).
680 patients over 16 months from 12 different centers.
24-hour Mortality: 12.7% (1:1:1 group) vs. 17% (1:1:2 group)
30-day Mortality 22.4% (1:1:1 group) vs. 26.1% (1:1:2 group)
Neither primary outcome was found to be statistically significantly different.
24-hour Death by Exsanguination: 9.2% (1:1:1 group) vs. 14.6% (1:1:2 group)
This secondary outcome was found to be statistically significantly different.
Safety Issues: No difference in the rates of bad outcomes secondary to transfusion (ARDS, thromboembolic events etc.)
- Large, multicenter trial
- Study asked a clear clinical question that was patient centered
- Reasonable exclusions increasing applicability
- Outcome measures were objective reducing bias
- Follow up was complete
- Underpowered to find small, but clinically significant, differences between the treatment arms
Sample Size + Power
- 95% power to detect a 10% difference in mortality at 24 hours
- 92% power to detect a 12% difference in mortality at 30 days
“Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ration 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 at 24 hours.”
This is the best study to date investigating the optimal transfusion of blood products in patients with severe traumatic injuries. Despite not finding a difference in their primary outcomes, the authors should be commended for their efforts. The study was powered to find a 10% difference in mortality at 24 hours and 12% mortality at 30 days. These differences are large and perhaps asking too much from a single intervention. The authors would have had to enroll about 3000 patients to power the study to find the 4% difference seen here. Although it was a secondary outcome, death from exsanguination appears to be decreased with the 1:1:1 transfusion approach.
Potential Impact To Current Practice
Although the study did not find a statistically significant difference between the two approaches, the small difference in death along with the absence of increased adverse events will likely drive many trauma centers to embrace the 1:1:1 transfusion strategy.
Based on the available evidence it is reasonable to adopt a 1:1:1 plasma:platelet:PRBC transfusion strategy. A larger RCT powered to detect smaller, but still clinically significant differences is needed.