Tranexamic acid administration in the field does not affect admission thromboelastography after traumatic brain injury

Journal of Trauma and Acute Care Surgery - Tập 89 Số 5 - Trang 900-907 - 2020
Alexandra Dixon1, Belinda H. McCully, Elizabeth A. Rick, Elizabeth N. Dewey, David H. Farrell, Laurie J. Morrison, Jason T. McMullan, Bryce R. H. Robinson, Jeannie Callum, Brian Tibbs, David J. Dries, Jonathan Jui, Rajesh R. Gandhi, John S. Garrett, Myron L. Weisfeldt, Charles E. Wade, Tom P. Aufderheide, Nicolas Segal, John M. Tallon, Delores Kannas, Clifton W. Callaway, Susan Rowell, Martin A. Schreiber
1From the Departments of Surgery (A.L.D., B.H.M., E.A.R., E.D., D.H.F., S.E.R., M.A.S., M.F.) and Emergency Medicine (J. Jui), Oregon Health and Science University, Portland, Oregon; Departments of Emergency Medicine (J.M.) and Surgery (J. Johannigman), University of Cincinnati, Cincinnati, Ohio; Departments of Surgery (B.R.H.R., E.M.B., P.K.) and Biostatistics (D.K., B.M., E.N.M., S.M., K.S., J.H.), University of Washington, Seattle, Washington; Trauma Surgery (B.T.), Texas Health Presbyterian Hospital; Department of Emergency Medicine (J.S.G.), Baylor University Medical Center, Dallas, Texas; Johns Hopkins School of Medicine (M.L.W.), Baltimore, Maryland; Department of Emergency Medicine (T.P.A., M.R.C.), Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Emergency Medicine (J.M.T., J.C.), University of British Columbia, Vancouver, British Columbia, Canada; Department of Surgery (S.E.R.), Scripps Memorial Hospital La Jolla, La Jolla, California; Departments of Emergency Medicine (A.H.I.) and Internal Medicine (A.H.I.), University of Texas Southwestern Medical Center, Dallas, Texas; Providence Health Care Research Institute (J.C.), Vancouver, British Columbia, Canada; Rescu, Li Ka Shing Knowledge Institute (L.J.M.), and Department of Surgery (S.R.), St. Michael's Hospital; Division of Emergency Medicine, Department of Medicine Faculty of Medicine (L.J.M.), and Department of Laboratory Medicine and Pathobiology (J.C.), University of Toronto, Toronto, Ontario, Canada; Departments of Emergency Medicine (R.J.F.) and Surgery (D.J.D.), Regions Hospital, St. Paul, Minnesota; Department of Surgery (C.W., P.L.B.), University of Alabama, Birmingham, Alabama; Department of Surgery (C.E.W., B.A.C., L.E.V.), McGovern Medical School, University of Texas Health Science Center, Houston, Texas; Department of Laboratory Medicine and Molecular Diagnostics (J.C.), Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Departments of Emergency Medicine (N.J.R.) and Surgery (R.R.G.), John Peter Smith Health Network, Fort Worth, Texas; Department of Surgery (M.D.Z., M.F.), Mayo Clinic, Rochester, Minnesota; British Columbia Emergency Health Services (J.M.T., R.S.), Vancouver, British Columbia, Canada; Department of Emergency Medicine (L.K., A.H.), Hennepin County Medical Center, Minneapolis, Minnesota; Department of Surgery (S.R.), St. Michael's Hospital, Toronto, Ontario, Canada; Department of Emergency Medicine (M.G.), Medical City Plano, Plano; Emergency

Tóm tắt

BACKGROUND No Food and Drug Administration–approved medication improves outcomes following traumatic brain injury (TBI). A forthcoming clinical trial that evaluated the effects of two prehospital tranexamic acid (TXA) dosing strategies compared with placebo demonstrated no differences in thromboelastography (TEG) values. We proposed to explore the impact of TXA on markers of coagulation and fibrinolysis in patients with moderate to severe TBI. METHODS Data were extracted from a placebo-controlled clinical trial in which patients 15 years or older with TBI (Glasgow Coma Scale, 3–12) and systolic blood pressure of ≥90 mm Hg were randomized prehospital to receive placebo bolus/placebo infusion (placebo), 1 g of TXA bolus/1 g of TXA infusion (bolus maintenance), or 2 g of TXA bolus/placebo infusion (bolus only). Thromboelastography was performed, and coagulation measures including prothrombin time, activated partial thromboplastin time, international ratio, fibrinogen, D-dimer, plasmin-antiplasmin (PAP), thrombin antithrombin, tissue plasminogen activator, and plasminogen activator inhibitor 1 were quantified at admission and 6 hours later. RESULTS Of 966 patients receiving study drug, 700 had laboratory tests drawn at admission and 6 hours later. There were no statistically significant differences in TEG values, including LY30, between groups (p > 0.05). No differences between prothrombin time, activated partial thromboplastin time, international ratio, fibrinogen, thrombin antithrombin, tissue plasminogen activator, and plasminogen activator inhibitor 1 were demonstrated across treatment groups. Concentrations of D-dimer in TXA treatment groups were less than placebo at 6 hours (p < 0.001). Concentrations of PAP in TXA treatment groups were less than placebo on admission (p < 0.001) and 6 hours (p = 0.02). No differences in D-dimer and PAP were observed between bolus maintenance and bolus only. CONCLUSION While D-dimer and PAP levels reflect a lower degree of fibrinolysis following prehospital administration of TXA when compared with placebo in a large prehospital trial of patients with TBI, TEG obtained on admission and 6 hours later did not demonstrate any differences in fibrinolysis between the two TXA dosing regimens and placebo. LEVEL OF EVIDENCE Diagnostic test, level III.

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2013, Traumatic brain injury and its effect on coagulopathy, Semin Thromb Hemost, 39, 896, 10.1055/s-0033-1357484

2010, Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial, Lancet, 376, 23, 10.1016/S0140-6736(10)60835-5

2012, Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) study, Arch Surg, 147, 113, 10.1001/archsurg.2011.287

2012, CRASH-2 (Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage) intracranial bleeding study: the effect of tranexamic acid in traumatic brain injury—a nested randomised, placebo-controlled trial, Health Technol Assess, 16, iii

2019, Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial, Lancet, 394, 1713, 10.1016/S0140-6736(19)32233-0

2013, Fibrinolysis greater than 3% is the critical value for initiation of antifibrinolytic therapy, J Trauma Acute Care Surg, 75, 961, 10.1097/TA.0b013e3182aa9c9f

2018, Fibrinolysis in trauma: a review, Eur J Trauma Emerg Surg, 44, 35, 10.1007/s00068-017-0833-3

2014, Hyperfibrinolysis, physiologic fibrinolysis, and fibrinolysis shutdown: the spectrum of postinjury fibrinolysis and relevance to antifibrinolytic therapy, J Trauma Acute Care Surg, 77, 811, 10.1097/TA.0000000000000341

2015, Basic mechanisms and regulation of fibrinolysis, J Thromb Haemost, 13, S98

2015, Endogenous plasminogen activators mediate progressive intracerebral hemorrhage after traumatic brain injury in mice, Blood, 125, 2558, 10.1182/blood-2014-08-588442

2015, Postinjury fibrinolysis shutdown: rationale for selective tranexamic acid, J Trauma Acute Care Surg, 78, S65

2013, The incidence and magnitude of fibrinolytic activation in trauma patients, J Thromb Haemost, 11, 307, 10.1111/jth.12078

2015, Label-free kinetic studies of hemostasis-related biomarkers including D-dimer using autologous serum transfusion, PLoS One, 10, e0145012, 10.1371/journal.pone.0145012

2017, Plasmin(ogen) at the nexus of fibrinolysis, inflammation, and complement, Semin Thromb Hemost, 43, 135, 10.1055/s-0036-1592302

2013, Tranexamic acid and trauma: current status and knowledge gaps with recommended research priorities, Shock, 39, 121, 10.1097/SHK.0b013e318280409a

2017, Early tranexamic acid administration ameliorates the endotheliopathy of trauma and shock in an in vitro model, J Trauma Acute Care Surg, 82, 1080, 10.1097/TA.0000000000001445

2007, The endothelial glycocalyx: composition, functions, and visualization, Pflugers Arch, 454, 345, 10.1007/s00424-007-0212-8

2012, Endothelial glycocalyx degradation induces endogenous heparinization in patients with severe injury and early traumatic coagulopathy, J Trauma Acute Care Surg, 73, 60, 10.1097/TA.0b013e31825b5c10

2017, Sympathoadrenal activation and endotheliopathy are drivers of hypocoagulability and hyperfibrinolysis in trauma: a prospective observational study of 404 severely injured patients, J Trauma Acute Care Surg, 82, 293, 10.1097/TA.0000000000001304

2018, The temporal response and mechanism of action of tranexamic acid in endothelial glycocalyx degradation, J Trauma Acute Care Surg, 84, 75, 10.1097/TA.0000000000001726

2019, Tranexamic acid suppresses the release of mitochondrial DNA, protects the endothelial monolayer and enhances oxidative phosphorylation, J Cell Physiol, 234, 19121, 10.1002/jcp.28603

2016, Acute fibrinolysis shutdown after injury occurs frequently and increases mortality: a multicenter evaluation of 2,540 severely injured patients, J Am Coll Surg, 222, 347, 10.1016/j.jamcollsurg.2016.01.006