PROPPR

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Holcomb JB, et al. "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". JAMA. 2015. 313(5):471-482.
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Clinical Question

In trauma patients receiving massive transfusion support for hemorrhagic shock, is a 1:1:1 ratio of plasma, platelets, and red blood cells noninferior to a 1:1:2 ratio?

Bottom Line

Among patients with trauma suffering hemorrhagic shock, there was no difference in mortality at 24 hours or 30 days between a 1:1:1 and 1:1:2 administration of plasma, platelets, and red blood cells.

Major Points

Optimal blood product transfusion ratios in trauma patients with major bleeding are not known. Historically, relatively high ratios of RBCs to plasma had been used, placing a high value on volume resuscitation and restoration of oxygen carrying capacity of the blood. Data from military studies suggested that a more balanced ratio approaching that of whole blood was superior to historic ratios, chiefly through immediate correction of trauma-associated coagulopathy and prevention of dilutional coagulopathy. Whether other ratios may be superior to this approach had not been subjected to randomized study.

Published in 2015, the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial screened over 11,000 patients with major trauma-related bleeding seen in North America centers, and 680 patients met the study's eligibility criteria. Patients were randomly assigned either to a 1:1:1 or a 1:1:2 ratio of plasma, platelets, and RBCs. There were no significant differences in the study's primary outcomes of death at 24 hours (12.7% vs. 17.0%) or death at 30 days (22.4% vs. 26.1%). However, fewer deaths due to exsanguination were seen in the 1:1:1 group (9.2% vs. 14.6%; P=0.03). Receipt of RBCs was similar between groups, although the 1:1:1 group received more plasma and platelets within the first 24 hours. The study was well designed, and benefited from its large size, blinded treatment, and an informed consent exception which allowed for rapid participant enrollment.

Guidelines

As of September 2023, no guidelines have been published that reflect the results of this trial.

Design

  • Pragmatic, phase 3, multisite, randomized clinical trial
  • 680 patients (11,185 screened)
    • 1:1:1 arm (n=338)
    • 1:1:2 arm (n=342)
  • 12 level I trauma centers in North America
  • Enrollment: 2012-2013
  • Primary outcome: Death at 24 hours and 30 days

Population

Inclusion Criteria

  • Highest level trauma activation available at the facility
  • Estimated age ≥15 years or (if age unknown) weight ≥50 kg
  • Received at trauma center directly from scene of injury
  • At least 1 unit of any blood component transfused prior to hospital arrival or within 1 hour of admission
  • Assessment of Blood Consumption score of ≥20 or clinician judgment that there is a need for massive transfusion (≥10 units RBCs within 24 hours)

Exclusion Criteria

  • Received a lifesaving intervention from an outside hospital or health care facility
  • Had devastating injuries and expected to die within 1 hour of admission (eg, lethal traumatic brain injury)
  • Directly admitted from a correctional facility
  • Required a thoracotomy prior to receiving randomized blood products in the emergency department
  • <15 years or (if age unknown) weight <50 kg
  • Known pregnancy in the emergency department
  • Had burns covering >20% total body surface area
  • Suspected inhalation injury
  • Received >5 consecutive minutes of cardiopulmonary resuscitation (with chest compressions) prior to hospital arrival or within the emergency department
  • Known do-not-resuscitate order prior to randomization
  • Enrolled in a concurrent, ongoing, interventional, randomized clinical trial
  • Activated the opt-out process for the PROPPR trial (usually by wearing a bracelet given out at a community consent presentation)
  • >3 units of red blood cells given before randomization

Baseline Characteristics

Comparisons are 1:1:1 vs. 1:1:2 groups.

  • Both groups were predominantly male (77.8% and 82.7% respectively) and young (median age 34.5 and 34 respectively)
  • Median HR 115 and 113 respectively, median SBP 102 and 102 respectively, median DBP 70 and 68 respectively
  • Similar division of blunt (54.7% vs. 50.6%) vs. penetrating (46.4% vs. 50.6%) injury
  • Initial hemoglobins were similar (median 11.7 g/dL vs. 11.9 g/dL)
  • Injury Severity Scores were similar (median 26.5 vs. 26)

Interventions

  • Randomized patients to transfusion of blood products using 1:1:1 (plasma, platelets, red blood cells) vs. 1:1:2 ratio
  • For both groups transfusion was terminated at the discretion of the treating clinician when clinically indicated irrespective of ratio or partial blood container use.

Outcomes

Primary Outcome

Comparisons are 1:1:1 v. 1:1:2 groups.

Death at 24 hours
12.7% vs. 17.0% (-4.2% absolute difference, 95% CI 9.6% to 1.1%; P=NS)
Death at 30 days
22.4% vs. 26.1% (-3.7% absolute difference, 95% CI -10.2% to 2.7%; P=NS)

Secondary Outcomes

Comparisons are 1:1:1 v. 1:1:2 groups.

Achievement of hemostasis at 24 hours
86.1% vs. 78.1% (P=0.06)
Median time to hemostasis
105 vs. 100 minutes (P=0.44)
Median ventilator free days
8 vs. 7 days (P=0.14)
Median ICU-free days
5 vs. 4 days (P=0.10)
Disposition at 30 days
No significant differences
Median Glasgow Outcome Scale-Extended Score
4 vs. 4.5 (P=0.11)
23 pre-specified complications
No difference
Rate of death due to exsanguination at 24 hours
9.2% vs. 14.6% (P=0.03)

Subgroup Analysis

No subgroup analyses were reported.

Adverse Events

Comparisons are 1:1:1 v. 1:1:2 groups.

  • Transfusion-related metabolic complication (hypocalcemia or hyperkalemia): 15.7% vs. 17.3% (-7.2 to 4.1)
  • Acute lung injury: 13.9% vs. 16.7% (-8.3 to 2.7)
  • Acute respiratory distress syndrome: 13.6% vs. 14.0% (-5.7 to 4.9)
  • Transfusion-associated circulatory overload: 0.3% vs. 0% (-0.8 to 1.7)
  • Any complication: 87.9% vs. 90.6% (-7.6 to 1.9)

Criticisms

  • Powered to detect a 10% difference between groups, but smaller benefits could not be detected.
  • Not powered to be a safety study (ie, differences in rare complications would likely be undetected).
  • Clinicians were unblinded after randomization by delivery of blood products from blood bank.
  • Timing of blood product administration was affected by the study protocol, with the 1:1:1 group likely receiving platelets earlier and the 1:1:2 group receiving plasma earlier.

Funding

"PROPPR is a Resuscitation Outcomes Consortium (ROC) Protocol. ROC is funded by the National Heart, Lung, and Blood Institute (NHLBI), the United States' Department of Defense (DoD) and the Defence Research and Development Canada" per ClinicalTrials.gov

Further Reading