Is all plasma created equal? A pilot study of the effect of interdonor variability.

Abstract

Clinical benefits of plasma as an adjunct for treatment of hemorrhagic shock (HS) have been well established. However, its use is not without risk. Little is understood regarding the clinical implications of plasma variability. We hypothesized there to be interdonor variability in plasma that would impact endothelial and organ function postinjury. Pulmonary endothelial cells (ECs) were incubated with plasma from 24 random donors, and transendothelial electrical resistance was measured. Plasma units with a more or less protective effect on reducing EC permeability were selected for testing in vivo. Syndecan-1 and cytokines were measured. Mice underwent laparotomy and then HS followed by resuscitation with the selected plasma units and were compared with mice receiving no resuscitation and shams. Lung tissue was sectioned and stained for myeloperoxidase and pulmonary syndecan-1 and scored for lung histopathologic injury. Plasma from 24 donors revealed variability in the reversal of EC monolayer hyperpermeability; transendothelial electrical resistance for the more protective plasma was significantly higher than that for the less protective plasma (0.801 ± 0.022 vs. 0.744 ± 0.035; p = 0.002). Syndecan-1 was also markedly increased in the less protective compared with the more protective plasma (38427 ± 1257 vs. 231 ± 172 pg/mL, p < 0.001), while cytokines varied. In vivo, the more protective plasma mitigated lung histopathologic injury compared with the less protective plasma (1.56 ± 0.27 vs. 2.33 ± 0.47, respectively; p = 0.005). Similarly, myeloperoxidase was significantly reduced in the more protective compared with the less protective plasma group (2.590 ± 0.559 vs. 6.045 ± 1.885; p = 0.02). Lastly, pulmonary syndecan-1 immunostaining was significantly increased in the more protective compared with the less protective plasma group (20.909 ± 8.202 vs. 9.325 ± 3.412; p = 0.018). These data demonstrate significant interdonor variability in plasma that can adversely influence the protective effects of plasma-based resuscitation on HS-induced lung injury. This may have important implications for patient safety and clinical outcomes.