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Fresh frozen plasma and spray-dried plasma mitigate pulmonary vascular permeability and inflammation in hemorrhagic shock

Potter, Daniel R. PhD; Baimukanova, Gail MD, PhD; Keating, Sheila M. PhD; Deng, Xutao PhD; Chu, Jeffrey A.; Gibb, Stuart L. PhD; Peng, Zhanglong PhD; Muench, Marcus O. PhD; Fomin, Marina E. PhD; Spinella, Philip C. MD; Kozar, Rosemary MD, PhD; Pati, Shibani MD, PhD

Journal of Trauma and Acute Care Surgery: June 2015 - Volume 78 - Issue 6 - p S7–S17
doi: 10.1097/TA.0000000000000630
Original Articles

BACKGROUND In retrospective and prospective observational studies, fresh frozen plasma (FFP) has been associated with a survival benefit in massively transfused trauma patients. A dry plasma product, such as spray-dried plasma (SDP), offers logistical advantages over FFP. Recent studies on FFP have demonstrated that FFP modulates systemic vascular stability and inflammation. The effect of SDP on these measures has not been previously examined. This study compares SDP with FFP using in vitro assays of endothelial function and in vivo assays of lung injury using a mouse model of hemorrhagic shock (HS) and trauma.

METHODS FFP, SDP, and lactated Ringer’s (LR) solution were compared in vitro using assays of endothelial cell (EC) permeability, cytokine production and content, gene expression, as well as tight and adherens junction stability. All resuscitation products were also compared in a murine model of HS. Mean arterial pressures and physiologic measures were assessed. Pulmonary vascular permeability was measured using tagged dextran. Lung tissues were stained for CD68, VE-cadherin, and occludin.

RESULTS Treatment of ECs with FFP and SDP, but not LR, preserved the integrity of EC monolayers in vitro and resulted in similar EC gene expression patterns and cytokine/growth factor production. FFP and SDP also reduced HS-induced pulmonary vascular permeability in vivo to the same extent. In mice with HS, mean arterial pressures and base excess were corrected by both FFP and SDP to levels observed in sham-treated mice. Treatment after HS with FFP and SDP but not LR solution reduce alveolar wall thickening, leukocyte infiltration, and the breakdown of EC junctions, as measured by staining for VE-cadherin, and occludin.

CONCLUSION Both FFP and SDP similarly modulate pulmonary vascular integrity, permeability, and inflammation in vitro and in vivo in a murine model of HS and trauma.

Supplemental digital content is available in the text.

From the Blood Systems Research Institute (D.R.P., G.B., S.M.K., X.D., J.A.C., S.L.G., M.O.M., M.E.F., S.P.); and Department of Laboratory Medicine (M.O.M., S.P.), University of California San Francisco, San Francisco, California; Department of Surgery (Z.P.), University of Texas-Houston Medical School, Houston, Texas; Division of Critical Care Medicine (P.C.S.), Department of Pediatrics, Washington School of Medicine, St. Louis, Missouri; and Shock Trauma Center (R.K.), University of Maryland, Baltimore, Maryland.

Submitted: October 30, 2014, Revised: February 2, 2015, Accepted: February 17, 2015.

Presented at the 4th Annual Remote Damage Control Resuscitation Symposium of the Trauma Hemostasis and Oxygenation Research Network, June 9–11, 2014, in Bergen, Norway.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (

Address for reprints: Shibani Pati, MD, PhD, Blood Systems Research Institute, 270 Masonic Ave, San Francisco, CA 94118; email:

© 2015 Lippincott Williams & Wilkins, Inc.