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Multiple Levels of Degradation Diminish Hemostatic Potential of Thawed Plasma

Matijevic, Nena PharmD, PhD; Kostousov, Vadim MD; Wang, Yao-Wei W. MD; Wade, Charles E. PhD; Wang, Weiwei PhD; Letourneau, Phillip MD; Hartwell, Elizabeth MD; Kozar, Rosemary MD, PhD; Ko, Tien MD; Holcomb, John B. MD

The Journal of Trauma: Injury, Infection, and Critical Care: January 2011 - Volume 70 - Issue 1 - p 71-80
doi: 10.1097/TA.0b013e318207abec
Original Article
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Background: Severe bleeding after injury requires transfusion of blood products, including fresh frozen plasma (FFP). Many centers are keeping thawed plasma (TP) ready for massively transfused patients. According to the American Association of Blood Banks Standards, TP is approved for transfusion up to 5 days after thawing, when stored at 1°C to 6°C. However, there are no clinical data analyzing the effects of the approved 5-day storage on plasma. We hypothesize that the hemostatic potential (HP) of freshly thawed (FFP-0) was superior to plasma stored for 5 days (FFP-5).

Methods: FFP from 30 single donors were thawed at 37°C and kept at 1°C to 6°C for 5 days. HP was evaluated at day 0 and 5 by measuring kinetics of thrombin generation (TG), kinetics of clot formation by thromboelastography, clotting factors and inhibitors, and cell-derived microparticles (MPs) by flow cytometry.

Results: When comparing FFP-5 to FFP-0, FFP-5 exhibited only 40% of the potential of FFP-0 for TG (6.2 nM/min vs. 14.3 nM/min, p < 0.0001), a slower clotting response via thromboelastography (reaction time: 4.3 minutes vs. 3.2 minutes, p < 0.0001) and a longer delay in reaching maximum thrombus generation (5.7 minutes vs. 4.6 minutes, p < 0.01). Diminished HP was accompanied by a significant decline in multiple coagulation proteins, including FV, VII, VIII, von Willebrand factor, and free Protein S, by up to 30%, and a decrease of 50% in MP counts.

Conclusion: The HP and clot forming ability of TP significantly declined with storage. Hence, freshly TP may have a greater ability to restore hemostasis and correct coagulopathy compared with FFP-5. The clinical consequences for transfused patients deserve further exploration.

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

Submitted for publication September 26, 2010.

Accepted for publication November 19, 2010.

Supported by the US Department of Defense via a grant W81XWH-08-C-0712, titled PROMMTT (Prospective, Observational, Multi-center Massive Transfusion sTudy), and by the P50 GM38529 grant to Department of Surgery at the University of Texas Health Science Center-Houston from the National Institutes of Health.

Presented in parts as posters at the Shock Society meetings in San Antonio, TX, June 6–9, 2009, and Portland, OR, June 12–15, 2010.

Presented at the 69th Annual Meeting of the American Association for the Surgery of Trauma, September 22–25, 2010, Boston, Massachusetts.

Address for reprints: Nena Matijevic, PharmD, PhD, University of Texas Health Science Center-Houston, 6431 Fannin, MSB 5.240, Houston, TX 77030; email: nevenka.matijevic-aleksic@uth.tmc.edu.

© 2011 Lippincott Williams & Wilkins, Inc.