Early Inflammatory Activation of Platelets and Neutrophils by Volume Resuscitation in a Human Whole Blood Model Mimicking a Severe Trauma-related Micromilieu

Trauma-induced coagulopathy represents a serious complication of hemorrhagic shock, associated with increased mortality within the first six hours post injury. Evidence of coagulopathy is often observable at the scene or upon hospital admission, emphasizing a critical role of pre-hospital care. Since studies on the use of various blood products in pre-hospital care have shown contradictory results, we aimed to investigate the effects of different volume substitutes on the initial immune response within the intravascular immune system. In an ex vivo model of polytrauma, blood from healthy volunteers was subjected to a trauma-characteristic shock scenario including the addition of danger-associated molecular patterns, blood acidification, and volume resuscitation. Resuscitation strategies involved either sodium chloride, component therapy (a combination of fresh frozen plasma and red blood cells), or leukocyte-reduced fresh whole blood. Samples were analyzed following 60 min of incubation at 37 °C to determine clinically relevant blood parameters and the activation status of both cellular innate leukocyte and humoral cascade responses. The use of blood products demonstrated superiority over NaCl, resulting in less disruption of the hemostatic system, as evidenced by reduced platelet activation. In parallel, neutrophil granulocytes were less affected, showing decreased surface activation marker expression and lower levels of soluble activation markers. Furthermore, activation of the complement system was reduced when the volume was resuscitated with blood products. Taken together, these data indicate that the choice of volume substitution greatly impacts the stability of the intravascular innate immune system, highlighting the potential benefit of leukocyte-reduced whole blood resuscitation.