EvidenceAlerts

BACKGROUND: Trauma is a leading cause of morbidity and mortality worldwide. Research shows that haemorrhage and trauma-induced coagulopathy are reversible components of traumatic injury, if identified and treated early. Lack of consensus on definitions and transfusion strategies hinders the translation of this evidence into clinical practice.

OBJECTIVES: To assess the beneficial and harmful effects of transfusion strategies started within 24 hours of traumatic injury in adults (aged 16 years and over) with major bleeding.

SEARCH METHODS: CENTRAL, MEDLINE, Embase, five other databases, and three trial registers were searched on 20 November 2023. We also checked reference lists of included studies to identify any additional studies.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) of adults (aged 16 years and over) receiving blood products for the management of bleeding within 24 hours of traumatic injury.

DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology to perform the review and assessed the certainty of the evidence using GRADE.

MAIN RESULTS: We included 18 RCTs with 5041 participants. Comparison 1: Prehospital transfusion strategies Five studies compared use of plasma (fresh frozen plasma (FFP) or lyophilised plasma) versus 'standard of care'. We are uncertain of the effect of plasma on all-cause mortality at 24 hours (risk ratio (RR) 1.05, 95% confidence interval (CI), 0.48 to 2.30; 3 studies, 279 participants; very low certainty evidence). There is probably no difference between plasma and standard of care in all-cause mortality at 30 days (RR 0.95, 95% CI 0.78 to 1.17; 3 studies, 664 participants; moderate-certainty evidence). However, the results of one cluster-RCT that could not be included in our meta-analysis suggested that plasma may be associated with a lower risk of death at 30 days (RR 0.54, 95% CI 0.42 to 0.70; 1 study, 481 participants; low-certainty evidence). There may be no difference between plasma and standard of care in the total number of thromboembolic events in 30 days (RR 1.23, 95% CI 0.67 to.2.27; 4 studies, 586 participants; low-certainty evidence). Comparison 2: In-hospital transfusion strategies Ten studies evaluated this comparison, seven providing usable data. The studies evaluated cryoprecitate (three studies); fixed-ratio blood component transfusion (three studies); fresh frozen plasma (FFP) (one study); lyophilised plasma (one study); leucoreduced red blood cells (one study); and a restrictive transfusion strategy (one study). All-cause mortality at 24 hours For all-cause mortality at 24 hours, there is probably no difference between: • cryoprecipitate plus a major haemorrhage protocol (MHP) versus MHP alone (RR 0.92, 95% CI 0.70 to 1.21; 1 study, 1577 participants; moderate-certainty evidence); and • blood products (plasma:platelets:red blood cells (RBCs)) transfused in 1:1:1 ratio versus 1:1:2 ratio (RR 0.75, 95% CI 0.52 to 1.08; 1 study, 680 participants; moderate-certainty evidence). We are uncertain of the effect on all-cause mortality at 24 hours for: • blood products (RBCs:FFP) transfused in 1:1 ratio versus transfusion according to coagulation and full blood count results (Peto odds ratio (POR) 0.45, 0.17 to 1.22; 1 study, 434 participants; very low certainty evidence); and • lyophilised (FlyP) plasma versus FFP (POR 1.04, 95% CI 0.06 to 17.23; 1 study, 47 participants; very low certainty evidence); All-cause mortality at 30 days For all-cause mortality at 30 days, there is probably no difference between blood products (plasma:platelets:RBCs) transfused in a 1:1:1 ratio versus a 1:1:2 ratio (RR 0.85, 95% CI 0.65 to 1.11; 1 study, 680 participants; moderate-certainty evidence). There may be little to no difference between the following interventions in all-cause mortality at 30 days: • cryoprecipitate plus MHP versus MHP alone (RR 0.77, 95% CI 0.33 to 1.78; 2 studies, 1572 participants; low-certainty evidence); and •leucoreduced RBCs versus standard RBCs (RR 1.20, 95% CI 0.74 to 1.95; 1 study,55 participants; low certainty evidence). We are uncertain of the effect on all-cause mortality at 30 days for: •lyophilised plasma versus FFP (RR 0.75, 95% CI 0.28 to 2.02; 1 study, 47 participants; very low certainty evidence); and • blood products (plasma:platelets:RBCs) transfused in 1:1:1 ratio versus standard MHP (RR 2.25, 95% CI 0.90 to 5.62; 1 study, 69 participants; very low certainty evidence). Total number of thromboembolic events at 30 days There may be little to no difference between the following interventions for total thromboembolic events at 30 days: • cryoprecipitate plus MHP versus MHP alone (RR 0.55, 95% CI 0.08 to 3.72; 2 studies, 1645 participants; low-certainty evidence); and • blood products (plasma:platelets:RBCs) transfused in 1:1:1 ratio versus 1:1:2 ratio (RR 1.03, 95% CI 0.75 to 1.42; 1 study, 680 participants; low-certainty evidence). We are uncertain of the effect on the total number of thromboembolic events at 30 days for: •blood products (plasma:platelets:RBCs) transfused in 1:1:1 ratio versus standard MHP (POR 6.83, 95% CI 0.68 to 68.35; 1 study, 69 participants; very low certainty evidence). Comparison 3: Whole blood versus individual blood products We are uncertain of the effect of modified (leucoreduced) whole blood versus blood products (RBCs:plasma) transfused in a 1:1 ratio on all-cause mortality at 24 hours (RR 1.13, 95% CI 0.37 to 3.49) or 30 days (RR 1.62, 95% CI 0.69 to 3.80) (1 study, 107 participants; very low certainty evidence). Comparison 4: Goal-directed blood transfusion strategy of viscoelastic haemostatic assay (VHA) versus conventional laboratory coagulation tests (CCT) to guide haemostatic therapy There may be little or no difference in all-cause mortality at 24 hours between VHA and CCT (RR 0.85, 95% CI 0.54 to 1.35; 1 study, 396 participants; low-certainty evidence). We are uncertain of the effects on all-cause mortality at 30 days (RR 0.75, 95% CI 0.48 to 1.17; 2 studies, 506 participants; very low certainty evidence). There is probably no difference between VHA and CCT in total thromboembolic events at 30 days (RR 0.65, 95% CI 0.35 to 1.18; 1 study 396 participants; moderate-certainty evidence).

AUTHORS' CONCLUSIONS: Overall, there was little to no evidence of a difference between blood transfusion strategies for mortality or thromboembolic events. The studies covered a wide range of interventions, and the comparators and standard of care practice varied between trials, thereby limiting the pooling of data. Further research is needed.

Anesthesiology rater

This Cochrane Review of literature relevant to transfusion strategy for trauma patients dispassionately summarizes the high variability and limited results of trauma trials. I believe the lede is buried by the data. In the background of all of these protocols have been unmeasured (and maybe unstudy-able) changes in practice: widespread adoption of MTPs to get blood to the OR quickly; ready availability of whole blood and plasma at the point of care; increased emphasis on early identification and mitigation of coagulopathy. This has led to huge improvements in outcome for trauma patients as a whole, but not attributable to any discrete factor. Elevation of the pragmatic standard of care (e.g., by MTPs) also makes it progressively more difficult to study new interventions: PROPPR would have shown a huge difference if 1:1:1 was compared with the very late plasma and platelet transfusion of the earlier era, rather than 1:1:2 that was already a substantial advance.

Emergency Medicine rater

A recurring issue across the various outcomes is the significant imprecision of the findings. The optimal size of the information (OSI) is clearly well below what is needed to support more informed decision-making in this context. In several scenarios, the problem is likely more a lack of robust evidence than a true absence of effect.

Pediatric Emergency Medicine rater

Although this study touches minimally on the paediatric age group, it still adds value because many teenagers suffer extensive trauma at sporting events and require blood transfusions. This study lays the foundation for a research question to address paediatric trauma outcomes after extensive hemorrhage and blood transfusion.

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