Abstract

BackgroundPlatelet dysfunction importantly contributes to trauma-induced coagulopathy (TIC). Our aim was to examine the impact of transfusing platelets (PLTs) in a 2:1 PLT-to-red blood cell (RBC) ratio versus the standard 1:1 ratio on transfusion requirements, correction of TIC, and organ damage in a rat multiple trauma transfusion model.MethodsMechanically ventilated male Sprague Dawley rats were traumatized by crush injury to the small intestine and liver and a fracture of the femur, followed by exsanguination until a mean arterial pressure (MAP) of 40 mmHg. Animals were randomly assigned to receive resuscitation in a high PLT dose (PLT to plasma to RBC in a ratio of 2:1:1) or a standard PLT dose (ratio of 1:1:1) until a MAP of 60 mmHg was reached (n = 8 per group). Blood samples were taken for biochemical and thromboelastometry (ROTEM) assessment. Organs were harvested for histopathology.Outcome measures were transfusion requirements needed to reach a pretargeted MAP, as well as ROTEM correction and organ failure.ResultsTrauma resulted in coagulopathy as assessed by deranged ROTEM results. Mortality rate was 19%, with all deaths occurring in the standard dose group. The severity of hypovolemic shock as assessed by lactate and base excess was not different in both groups. The volume of transfusion needed to reach the MAP target was lower in the high PLT dose group compared to the standard dose, albeit not statistically significant (p = 0.054). Transfusion with a high PLT dose resulted in significant stronger clot firmness compared to the standard dose at all time points following trauma, while platelet counts were similar. Organ failure as assessed by biochemical analysis and histopathology was not different between groups, nor were there any thromboembolic events recorded.ConclusionsResuscitation with a high (2:1) PLT-to-RBC ratio was more effective compared to standard (1:1) PLT-to-RBC ratio in treating TIC, with a trend towards reduced transfusion volumes. Also, high PLT dose did not aggravate organ damage. Transfusion strategies using higher PLT dose regiments might be a feasible treatment option in hemorrhaging trauma patients for the correction of TIC.

Highlights

  • Platelet dysfunction importantly contributes to trauma-induced coagulopathy (TIC)

  • The PROPPR trial showed that a balanced resuscitation approach using platelets (PLT), plasma, and red blood cell (RBC) in a 1:1:1 ratio was more effective in achieving hemostasis than a lower 1:1:2 ratio [11]

  • These findings indicate that an impaired platelet function may be one of the key elements driving TIC and subsequent adverse outcomes

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Summary

Introduction

Platelet dysfunction importantly contributes to trauma-induced coagulopathy (TIC). Our aim was to examine the impact of transfusing platelets (PLTs) in a 2:1 PLT-to-red blood cell (RBC) ratio versus the standard 1:1 ratio on transfusion requirements, correction of TIC, and organ damage in a rat multiple trauma transfusion model. The PROPPR trial showed that a balanced resuscitation approach using platelets (PLT), plasma, and RBC in a 1:1:1 ratio was more effective in achieving hemostasis than a lower 1:1:2 ratio [11]. These findings were confirmed in observational studies in both military and civilian trauma cohorts, suggesting an improved survival when higher PLT-to-RBC ratios (1:1) were used [12, 13]. Dysfunctional platelets are independently associated with mortality in trauma patients [15] These findings indicate that an impaired platelet function may be one of the key elements driving TIC and subsequent adverse outcomes. HMGB-1 is increased and was found to be a key player in thrombus formation in mice [17]

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