Systemic Hyperfibrinolysis after Trauma: A Pilot study of Targeted Proteomic Analysis of Superposed Mechanisms in Patient Plasma

Background Viscoelastic measurements of hemostasis indicate that 20% of seriously injured patients exhibit systemic hyperfibrinolysis, with increased early mortality. These patients have normal clot formation with rapid clot lysis. Targeted proteomics was applied to quantify plasma proteins from hyperfibrinolytic (HF) patients to elucidate potential pathophysiology. Methods Blood samples were collected in the field or at Emergency Department arrival and thrombelastography (TEG) was used to characterize in vitro clot formation under native and tissue plasminogen activator (tPA)-stimulated conditions. Ten samples were taken from injured patients exhibiting normal lysis time at 30 min (Ly30), “eufibrinolytic” (EF), 10 from HF patients, defined as tPA-stimulated TEG Ly30 >50%, and 10 from healthy controls. Trauma patient samples were analyzed by targeted proteomics and ELISA assays for specific coagulation proteins. Results HF patients exhibited increased plasminogen activation. Thirty-three proteins from the HF patients were significantly decreased compared to healthy controls and EF patients; 17 were coagulation proteins with anti-protease consumption (p0.1 and fold change of concentrations of 0.75-1.3). Conclusion HF patients had significant decreases in specific proteins and support mechanisms known in trauma-induced hyperfibrinolysis and also unexpected decreases in coagulation factors, factors II, X, and XIII, without changes in clot formation (SP, R times or angle). Decreased clot stability in HF patients was corroborated with tPA-stimulated TEGs. Level of Evidence III prognostic. Correspondence: Anirban Banerjee, PhD, Department of Surgery, School of Medicine, UCD, 12700 E 19th Ave. Mail Stop C320, Aurora, CO 80045, E-mail anirban.banerjee@ucdenver.edu The authors have no conflict of interest with the submitted work. This work was supported by grants P50 GM049222, NIGMS, NIH, T32 GM008315, NIGMS, NIH, and UM1-HL120877, NHLBI, NIH and the Department of Surgery and the Colorado Clinical and Translational Sciences Institute, School of Medicine, University of Colorado Denver, and Bonfils Blood Center. Both AB and CCS wrote the manuscript and contributed equally so that they should be co-first authors, Anirban Banerjee PhD; Christopher C Silliman MD, PhD. © 2018 Lippincott Williams & Wilkins, Inc.

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