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Plasma Co-Administration Improves Resuscitation with Tranexamic Acid or Prothrombin Complex in a Porcine Hemorrhagic Shock Model

John P Kuckelman, Morgan Barron, MD, Donald Moe, Michael Lallemand, John McClellan, Shannon Marko, Matthew Eckert, Matthew Martin. Madigan Army Medical Center

OBJECTIVE: Traumatic coagulopathy has now been well characterized, but still carries high rates of mortality due to bleeding. A "factor-based" resuscitation strategy using pro-coagulant drugs and factor concentrates in lieu of plasma is being used by some, but with little evidentiary support. We sought to evaluate and compare resuscitation strategies using combinations of tranexamic acid (TXA), prothrombin complex concentrate (PCC), and fresh frozen plasma (FFP).

METHODS: A 35% blood volume hemorrhage combined with a truncal ischemia-reperfusion injury was utilized in 60 adult swine to produce uniform shock and coagulopathy. Animals were randomized to control (N=12), a single agent group (TXA, N=10, PCC, N=8, or FFP, N=6) or combination groups (TXA-FFP, N=10, PCC-FFP, N=8, TXA-PCC, N=6).  Resuscitation was continued to 6 hours. Key outcomes included hemodynamics, lab values, and thromboelastometry (ROTEM). Results were compared between all groups, with additional comparisons between FFP and non-FFP groups.

RESULTS: All 60 animals survived to 6 hours. Shock was seen in all animals, with hypotension (MAP 44mmHg), tachycardia (HR 145), acidosis (pH 7.18, lactate 11), anemia (HCT 17), and coagulopathy (Fibrinogen 107). There were clear differences between groups for mean pH (p=0.02), INR (p<0.01), clotting time (CT, p<0.01), lactate (p=0.01), creatinine (p<0.01), and fibrinogen (p=0.02). FFP groups had significantly improved resuscitation and clotting parameters with lower lactate 6.5 vs 8.4 (p=0.04), and increased fibrinogen at 126 vs 95 (p<0.01). ROTEM also demonstrated shortened CT at 60s in the FFP group vs 65s in the non-FFP group (p=0.04).

CONCLUSION: When used to correct traumatic coagulopathy, combinations of FFP with TXA or PCC were superior in improving acidosis, coagulopathy, and clotting time than when these agents are given alone or in combo without plasma. Further validation of pure "factor-based" strategies is needed.


Presented at the SAGES 2017 Annual Meeting in Houston, TX.

Abstract ID: 87120

Program Number: MSS07

Presentation Session: Full-Day Military Surgical Symposium – Basic Science Presentations

Presentation Type: MSSPodium

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