131 Burn-Induced Coagulopathy: Burn Patient Plasma Causes Platelet Dysfunction

Abstract Introduction Burn-induced coagulopathy (BIC) greatly increases the risk of thrombosis, leading to organ dysfunction and death. Although BIC is attributed to a multitude of factors including hemodilution, SIRS, and excess coagulation, the exact molecular mechanisms are elusive. Determination of these mechanisms is essential to develop new strategies aimed at reducing the morbidity and mortality of BIC as commonly used anticoagulants are ineffective at preventing the consequences of BIC. Platelet dysfunction, which has been associated with bleeding, thrombosis, poor wound repair, and susceptibility to infection, occurs in BIC, but the etiology of this phenomenon is unknown. Burn injuries provoke a dramatic increase in plasma levels of inflammatory, coagulation, and fibrinolytic factors, potentially altering the physiology of blood cells and platelets. Therefore, we hypothesized that burn patient plasma pathologically alters normal platelet function. Methods In this prospective study, plasma samples were collected from 32 adult patients with burns >10% TBSA at a regional burn center. To assess the effects of burn plasma on platelet function, platelets isolated from healthy individuals were incubated with heparinized plasma from burn patients or control plasmas (N=15) for 2 hours. Following incubation, platelets were stimulated with various agonists, and markers of platelet activation (GPIIb/IIIa activation and P-selectin expression) were measured using flow cytometry. Results Platelets incubated with burn plasmas exhibited a reduction in response to stimulation compared with those incubated with control plasma. Both GPIIb/IIIa activation and P-selectin expression were affected, suggesting a defect in platelet signaling. This dysfunction did not strongly correlate with TBSA affected or modified Baux score but was significant when compared to healthy controls (P< 0.05). However, measurement of markers of inflammation, coagulation, and fibrinolysis in burn plasmas revealed a significant correlation of both plasma D-dimer (P< 0.02) and soluble P-selectin (P< 0.05) with induced platelet dysfunction. This suggests circulating factors indicative of coagulation, fibrinolysis, and endothelial dysfunction may play a role in platelet dysfunction observed in BIC. Conclusions This study demonstrates an in vitro effect of burn patient plasma on platelet function, suggesting a possible benefit for resuscitation with FFP. BIC is a principal source of morbidity and mortality in burn patients, and current thromboprophylaxis for burn patients may not address critical elements of BIC. Future studies are required to optimize resuscitation and minimize the consequences of BIC.