L. J. Schaub1, R. M. Paredes1, A. R. Macko1, J. J. Glaser1, H. B. Moore2,3, E. E. Moore2,3, F. R. Sheppard1 1Naval Medical Research Unit-San Antonio,Expeditionary And Trauma Medicine,Ft. Sam Houston, TX, USA 2Denver Health Medical Center,Surgery,Aurora, CO, USA 3University Of Colorado Denver,Surgery,Aurora, CO, USA
Introduction: Platelet dysfunction (PD) is a significant component of trauma induced coagulopathy (TIC). The conditions under which PD occurs and the role of platelet transfusion remain to be elucidated. We hypothesized that correction of PD may be determined by the metabolic state during resuscitation.
Methods: NHPs (n=8) underwent poly-traumatic (soft tissue injury and femur fracture) severe hemorrhagic shock (MAP=20mmHg). Resuscitation was accomplished via a combination of fresh whole blood (WB) and normal saline (NS), with resuscitation volume determined by shed blood volume (SBV). Arterial blood gas, complete blood count (CBC), lactate and Multiplate® platelet aggregation analyses were performed at baseline (BSLN), end of shock (EOS), end of resuscitation (EOR) and T=360min after initiation of shock. Multiplate platelet aggregation was determined by area under the aggregation curve in units (U) over a 6min measurement period and normalized to actual platelet count. Results reported as mean±SEM. Statistical analysis was performed by Spearmen correlation and one-way ANOVA with p<0.05 considered significant.
Results: Lactate and base deficit (BD) levels increased at EOS compared to BSLN. Lactate levels returned to BSLN levels by EOR. BD improved from a nadir at EOS but did not return to BSLN levels by T=360min. (Fig 1). Platelet aggregation decreased in response to adenosine diphosphate (ADP), collagen (COL), and arachidonic acid (AA), most notably following the initiation of resuscitation (Fig 1). Significant correlations were observed between platelet aggregation and BD: ADP (r=0.7070, p<0.0001), COL (r=0.6194, p=0.0002), and AA (r=0.4831, p=0.0051). In contrast, no significant correlations were observed between platelet aggregation and lactate: ADP (r=-0.2298, p=0.2058), COL (r=-0.3111, p=0.0830), and AA (r=-.0923, p=0.6156).
Conclusion: In this study, PD was observed at EOS with significant PD in response to all platelet agonists identified at EOR. Based on correction of lactate, by EOR aerobic metabolism was restored rapidly by resuscitation; however BD buffering was delayed. Platelet function correlated strongly with BD but not lactate, and the administration of platelets in WB did not correct PD. These data indicate that administration of platelets prior to correction of BD may be ineffective. This may be related to a residual byproduct of the shock state; e.g. metabolites from anaerobic metabolism, suggesting that the timing of platelet therapy may be important for optimal effectiveness.
