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Shock-induced systemic hyperfibrinolysis is attenuated by plasma-first resuscitation

Moore, Hunter B. MD; Moore, Ernest E. MD; Morton, Alexander P. MD; Gonzalez, Eduardo MD; Fragoso, Miguel DVM; Chapman, Michael P. MD; Dzieciatkowska, Monika PhD; Hansen, Kirk C. PhD; Banerjee, Anirban PhD; Sauaia, Angela MD, PhD; Silliman, Christopher C. MD, PhD

Journal of Trauma and Acute Care Surgery: December 2015 - Volume 79 - Issue 6 - p 897–904
doi: 10.1097/TA.0000000000000792
WTA Plenary Papers
Editor's Choice

BACKGROUND We developed a hemorrhagic shock animal model to replicate an urban prehospital setting where resuscitation fluids are limited to assess the effect of saline versus plasma in coagulopathic patients. An in vitro model of whole blood dilution with saline exacerbated tissue plasminogen activator (tPA)–mediated fibrinolysis, while plasma dilution did not change fibrinolysis. We hypothesize that shock-induced hyperfibrinolysis can be attenuated by resuscitation with plasma while exacerbated by saline.

METHODS Sprague-Dawley rats were hemorrhaged to a mean arterial pressure of 25 mm Hg and maintained in shock for 30 minutes. Animals were resuscitated with either normal saline (NS) or platelet-free plasma (PFP) with a 10% total blood volume bolus, followed by an additional 5 minutes of resuscitation with NS to increase blood pressure to a mean arterial pressure of 30 mm Hg. Animals were observed for 15 minutes for the assessment of hemodynamic response and survival. Blood samples were analyzed with thrombelastography paired with protein analysis.

RESULTS The median percentage of total blood volume shed per group were similar (NS, 52.5% vs. PFP, 55.7; p = 0.065). Survival was 50% in NS compared with 100% in PFP. The change in LY30 and tPA levels from baseline to shock was similar between groups (LY30 PFP, 10; interquartile range [IQR], 4.3–11.2; NS, 4.5; IQR, 4.1–14.2; p = 1.00; tPA PFP, 16.6 ng/mL; IQR, 13.7–27.8; NS, 22.4; IQR, 20.1–25.5; p = 0.240). After resuscitation, the median change in LY30 was greater in the NS group (13.5; IQR, 3.5–19.9) compared with PFP (−4.9%; IQR, −9.22 to 0.25 p = 0.004), but tPA levels did not significantly change (NS, 1.4; IQR, −6.2 to 7.1 vs. PFP, 1.7; IQR, −5.2 to 6.8; p = 0.699).

CONCLUSION Systemic hyperfibrinolysis is driven by hypoperfusion and associated with increased levels of tPA. Plasma is a superior resuscitation fluid to NS in a prehospital model of severe hemorrhagic shock as it attenuates hyperfibrinolysis and improves systemic perfusion.

From the Department of Surgery (H.B.M., E.E.M., A.P.M., E.G., M.F., M.P.C., M.D., K.C.H., A.B., A.S., C.C.S.), University of Colorado Denver, Denver Health Medical Center (H.B.M., E.E.M., A.P.M., E.G., M.F., M.P.C.), and Bonfils Blood Center (C.C.S.), Denver, Colorado.

Submitted: January 13, 2015, Revised: March 23, 2015, Accepted: June 3, 2015, Published online: October 1, 2015.

This study was presented at the 45th annual meeting of the Western Trauma Association, March 1–6, 2015, in Telluride, Colorado. Winner of the Earl G. Young Award.

The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Address for reprints: Ernest E. Moore, MD, 655 Broadway, Ste. 365 Denver, CO 80203; email:

© 2015 Lippincott Williams & Wilkins, Inc.