Use of a high platelet-to-RBC ratio of 2:1 is more effective in correcting trauma-induced coagulopathy than a ratio of 1:1 in a rat multiple trauma transfusion model

Abstract

Background 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. Methods Mechanically 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. Results Trauma 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. Conclusions Resuscitation 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.

The use of cryopreserved platelets in a trauma‐induced hemorrhage model

“…Forty syngeneic donor rats were used for the preparation of blood products as described before. 19,20 In short, whole blood was obtained through cardiac puncture and prepared and stored according to national blood bank standards. Whole blood was mixed in a 9-to-1 ratio with citrate-phosphate-dextrose solution, after which blood was immediately centrifuged (10 min, 1892G, 20°C) to separate the blood in three different components.…”

“…This scoring system has been used before. 19,20 The lung, for example, was scored based on lung edema, interstitial inflammatory cell infiltration, endothelialitis, and hemorrhage. The scale of each category consisted of a score of 0 (=absent) to 3 (=severe).…”

“…Based on previous experiments, 19 given a treatment effect of 0.6 mL/kg and a standard deviation of 0.47 mL/kg, 11 rats per group have a power of 80% to detect a statistical significant difference in transfusion volume needed to reach a MAP of 60 mmHg. Because we previously experienced a mortality of 20% in our model, we added two additional rats per group, yielding 13 per experimental group.…”

Bosutinib reduces endothelial permeability and organ failure in a rat polytrauma transfusion model

“…Transfusion products were made from syngeneic donor rats according to national blood bank standards as described. 20 …”

“…Trauma was induced by a fracture of the right femur using a guillotine, a crush injury to the small intestine and left lateral liver lobe as described 20 ( Supplementary Fig. S1 ).…”