Whole blood mitigates the acute coagulopathy of trauma and avoids the coagulopathy of crystalloid resuscitation.

INTRODUCTION: The contributions of type and timing of fluid resuscitation to coagulopathy in trauma remain controversial. As part of a multifunctional resuscitation fluid research effort, we sought to further characterize the coagulation responses to resuscitation, specifically as compared to whole blood. We hypothesized that early whole blood administration mitigates the acute coagulopathy of trauma by avoiding the coagulopathy of CR resuscitation. METHODS: Anesthetized rhesus macaques underwent polytraumatic, hemorrhagic shock, then a crossover study design resuscitation (n = 6 each) with either whole blood first (WB-1st) followed by crystalloid (CR); or CR-1st followed by WB. Resuscitation strategies were the following: WB-1st received 50% shed blood in 30minutes, followed by twice the shed blood volume (SBV) of CR over 30minutes and one times the SBV CR over 60minutes, where CR-1st received twice the SBV of CR over 30minutes, followed by 50% of shed blood in 30minutes, and one times the SBV CR over 60minutes. Blood samples were collected at baseline, end-of-shock, end-of-first and end-of-second resuscitation stages, and end-of-resuscitation for assessment (thromboelastometry, platelet aggregation, and plasmatic coagulation factors). Statistical analyses were conducted using two-way analysis of variance ANOVA with Bonferroni correction and t-tests; significance was at p < 0.05. RESULTS: Survival, blood loss, hemodynamics, and shock duration were equivalent between the groups. Compared to baseline, parameters measured at first and second resuscitation stage time points directly following CR infusion revealed abnormalities in thromboelastometry (clot formation time, α angle, and maximum clot firmness), platelet aggregation response (to collagen, arachidonic acid, and adenosine diphosphate), and plasmatic coagulation (prothrombin time, anti-thrombin 3, and fibrinogen), while whole blood infusion resulted in stabilization or correction of these parameters following its administration. CONCLUSIONS: These data suggest that in the setting of trauma and hemorrhagic shock, the coagulation alterations begin before intervention/resuscitation; however, these are significantly aggravated by CR resuscitation and could perhaps be best termed acute coagulopathy of resuscitation. STUDY TYPE: Translational animal model.

Application of phage display for the development of a novel inhibitor of PLA2 activity in Western cottonmouth venom.

Snakebite envenomation is an important global health concern. The current standard treatment approach for snakebite envenomation relies on antibody-based antisera, which are expensive, not universally available, and can lead to adverse physiological effects. Phage display techniques offer a powerful tool for the selection of phage-expressed peptides, which can bind with high specificity and affinity towards venom components. In this research, the amino acid sequences of Phospholipase A2 (PLA2) from multiple cottonmouth species were analyzed, and a consensus peptide synthesized. Three phage display libraries were panned against this consensus peptide, crosslinked to capillary tubes, followed by a modified surface panning procedure. This high throughput selection method identified four phage clones with anti-PLA2 activity against Western cottonmouth venom, and the amino acid sequences of the displayed peptides were identified. This is the first report identifying short peptide sequences capable of inhibiting PLA2 activity of Western cottonmouth venom in vitro, using a phage display technique. Additionally, this report utilizes synthetic panning targets, designed using venom proteomic data, to mimic epitope regions. M13 phages displaying circular 7-mer or linear 12-mer peptides with antivenom activity may offer a novel alternative to traditional antibody-based therapy.