Journal
JOURNAL OF TRAUMA AND ACUTE CARE SURGERY
Volume 84, Issue 6, Pages 929-938Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/TA.0000000000001878
Keywords
Coagulation; targeted proteomics; fibrinolysis; traumatic injury
Categories
Funding
- NIGMS, NIH [P50 GM049222, T32 GM008315]
- NHLBI, NIH [UM1-HL120877]
- Department of Surgery
- Colorado Clinical and Translational Sciences Institute, School of Medicine, University of Colorado Denver
- Bonfils Blood Center
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [UM1HL120877] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM008315, P50GM049222] Funding Source: NIH RePORTER
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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 with healthy controls and EF patients; 17 were coagulation proteins with anti-protease consumption (p < 0.005). The other 16 decreased proteins indicate activation of the alternate complement pathway, depletion of carrier proteins, and four glycoproteins. CXC7 was elevated in all injured patients versus healthy controls (p < 0.005), and 35 proteins were unchanged across all groups (p > 0.1 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 Prognostic, level III.
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