Blood products in trauma & survivor bias

Esky-label.001The observation that patients with haemorrhagic trauma in military and civilian settings do better if they receive coagulation factors and platelets is yet to be replicated in a randomised trial. It has been suggested that the effect may in part be a consequence of survivor bias – ie. that if a patient lives long enough to received some thawed fresh frozen plasma, then they were already more likely to be a survivor and therefore more survivors will be represented in the ‘FFP’ groups vs a ‘no-FFP’ comparison group.
An attempt to eliminate survivor bias was made in the PROMMTT study, which documented the timing of transfusions during active resuscitation and patient outcomes in adult trauma patients who received a transfusion of at least 1 unit of RBCs within 6 hours of admission.
Increased ratios of plasma:RBCs and platelets:RBCs were independently associated with decreased 6-hour mortality, when haemorrhagic 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.
A prospective trial is underway to identify the optimal ratio of blood products, in the PROPPR study, in which 1:1:1 ratio of plasma:platelets:RBC will be compared with 1:1:2.
The Prospective, Observational, Multicenter, Major Trauma Transfusion (PROMMTT) Study
Arch Surg. 2012 Oct 15:1-10
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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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