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Protective Effects of Fresh Frozen Plasma on Vascular Endothelial Permeability, Coagulation, and Resuscitation After Hemorrhagic Shock Are Time Dependent and Diminish Between Days 0 and 5 After Thaw

Pati, Shibani MD, PhD; Matijevic, Nena PhD; Doursout, Marie-Françoise PhD; Ko, Tien MD; Cao, Yanna MD; Deng, Xiyun PhD; Kozar, Rosemary A. MD, PhD; Hartwell, Elizabeth MD; Conyers, Jodie PhD; Holcomb, John B. MD

The Journal of Trauma: Injury, Infection, and Critical Care: July 2010 - Volume 69 - Issue 1 - p S55-S63
doi: 10.1097/TA.0b013e3181e453d4
Original Article

Background: Clinical studies have shown that resuscitation with fresh frozen plasma (FFP) is associated with improved outcome after severe hemorrhagic shock (HS). We hypothesized that in addition to its effects on hemostasis, FFP has protective and stabilizing effects on the endothelium that translate into diminished endothelial cell (EC) permeability and improved resuscitation in vivo after HS. We further hypothesized that the beneficial effects of FFP would diminish over 5 days of routine storage at 4°C.

Methods: EC permeability was induced by hypoxia and assessed by the passage of 70-kDa Dextran between monolayers. Thrombin generation time and coagulation factor levels or activity were assessed in FFP. An in vivo rat model of HS and resuscitation was used to determine the effects of FFP on hemodynamic stability.

Results: Thawed FFP inhibits EC permeability in vitro by 10.2-fold. Protective effects diminish (to 2.5-fold) by day 5. Thrombin generation time is increased in plasma that has been stored between days 0 and 5. In vivo data show that day 0 FFP is superior to day 5 FFP in maintaining mean arterial pressure in rats undergoing HS with resuscitation.

Conclusion: Both in vitro and in vivo studies show that FFP has beneficial effects on endothelial permeability, vascular stability, and resuscitation in rats after HS. The benefits are independent of hemostasis and diminish between days 0 and 5 of storage.

From the Department of Surgery and Center for Translational Injury Research (S.P., N.M., M.-F.D., T.K., Y.C., X.D., R.A.K., J.C., J.B.C.), University of Texas Health Science Center; and Gulf Coast Regional Blood Center (E.H.), Houston, Texas.

Submitted for publication March 18, 2010.

Accepted for publication April 22, 2010.

Supported by an NIH grant (NIGMS 5 P50 GM038529).

The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the US Department of the Air Force, Army, Navy, Defense, or the Government. This work was prepared as part of their official duties; and, as such, there is no copyright to be transferred.

Presented at the Conference on Shock, San Antonio, TX, June 2009.

Address for reprints: Shibani Pati, MD, PhD, University of Texas Health Science Center, 6410 Fannin, Suite 1100, Houston, TX 77030; email:

© 2010 Lippincott Williams & Wilkins, Inc.