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Original Article | ONLINE FIRST

The Prospective, Observational, Multicenter, Major Trauma Transfusion (PROMMTT) Study:  Comparative Effectiveness of a Time-Varying Treatment With Competing Risks

John B. Holcomb, MD; Deborah J. del Junco, PhD; Erin E. Fox, PhD; Charles E. Wade, PhD; Mitchell J. Cohen, MD; Martin A. Schreiber, MD; Louis H. Alarcon, MD; Yu Bai, MD, PhD; Karen J. Brasel, MD, MPH; Eileen M. Bulger, MD; Bryan A. Cotton, MD, MPH; Nena Matijevic, PhD; Peter Muskat, MD; John G. Myers, MD; Herb A. Phelan, MD, MSCS; Christopher E. White, MD; Jiajie Zhang, PhD; Mohammad H. Rahbar, PhD; for the PROMMTT Study Group
JAMA Surg. 2013;148(2):127-136. doi:10.1001/2013.jamasurg.387.
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Objective  To relate in-hospital mortality to early transfusion of plasma and/or platelets and to time-varying plasma:red blood cell (RBC) and platelet:RBC ratios.

Design  Prospective cohort study documenting the timing of transfusions during active resuscitation and patient outcomes. Data were analyzed using time-dependent proportional hazards models.

Setting  Ten US level I trauma centers.

Patients  Adult trauma patients surviving for 30 minutes after admission who received a transfusion of at least 1 unit of RBCs within 6 hours of admission (n = 1245, the original study group) and at least 3 total units (of RBCs, plasma, or platelets) within 24 hours (n = 905, the analysis group).

Main Outcome Measure  In-hospital mortality.

Results  Plasma:RBC and platelet:RBC ratios were not constant during the first 24 hours (P < .001 for both). In a multivariable time-dependent Cox model, increased ratios of plasma:RBCs (adjusted hazard ratio = 0.31; 95% CI, 0.16-0.58) and platelets:RBCs (adjusted hazard ratio = 0.55; 95% CI, 0.31-0.98) were independently associated with decreased 6-hour mortality, when hemorrhagic death predominated. In the first 6 hours, patients with ratios less than 1:2 were 3 to 4 times more likely to die than patients with ratios of 1:1 or higher. After 24 hours, plasma and platelet ratios were unassociated with mortality, when competing risks from nonhemorrhagic causes prevailed.

Conclusions  Higher plasma and platelet ratios early in resuscitation were associated with decreased mortality in patients who received transfusions of at least 3 units of blood products during the first 24 hours after admission. Among survivors at 24 hours, the subsequent risk of death by day 30 was not associated with plasma or platelet ratios.

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Figures

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Grahic Jump Location

Figure 1. Blood product use in the first 6 hours in 2 Prospective, Observational, Multicenter, Major Trauma Transfusion Study patients. Patient 1 (A) had an Injury Severity Score of 48 and died of hemorrhage at 1 hour 7 minutes after emergency department admission. Patient 2 (B) had an Injury Severity Score of 57 and was discharged to another acute care hospital at 27 days. Note the constantly changing ratios over time. For example, patient 1 received cumulative plasma:platelet:red blood cell (RBC) ratios of 0:0:1, 0:0:3, 0:0:6, 4:6:6, and 5:6:6 at 15, 30, 45, 60, and 75 minutes, respectively, while patient 2 received cumulative plasma:platelet:RBC ratios of 0:0:1, 0:0:4, 0:0:4, 2:0:6, and 2:0:10 at those same times.

Place holder to copy figure label and caption
Grahic Jump Location

Figure 2. The bars represent cumulative ratios at the start of each time interval. Most patients received a plasma:red blood cell (RBC) ratio of 1:2 or higher by 3 hours (A) and a platelet:RBC ratio of 1:2 or higher by 6 hours (B). In the last time interval (24 hours), the percentage of patients receiving 0 units of platelets or plasma increases, reflecting the dynamic cohort with newly eligible patients entering and others exiting owing to death in the previous interval.

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