Alexandra L Dixon1, Belinda H McCully, Elizabeth A Rick, Elizabeth Dewey, David H Farrell, Laurie J Morrison, Jason 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, Ralph J Frascone, John M Tallon, Delores Kannas, Carolyn Williams, Susan E Rowell, Martin A Schreiber. 1. From 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 Medicine (R.S.), Methodist Dallas Medical Center, Dallas, Texas; National Heart, Lung, and Blood Institute, National Institutes of Health (G.S.), Bethesda, Maryland; and Department of Trauma Surgery (W.W.), Texas Health Harris Methodist Hospital, Fort Worth, Texas.
Abstract
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.
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.
Authors: Ernest E Moore; Hunter B Moore; Eduardo Gonzalez; Michael P Chapman; Kirk C Hansen; Angela Sauaia; Christopher C Silliman; Anirban Banerjee Journal: J Trauma Acute Care Surg Date: 2015-06 Impact factor: 3.313
Authors: Hunter B Moore; Ernest E Moore; Eduardo Gonzalez; Michael P Chapman; Theresa L Chin; Christopher C Silliman; Anirban Banerjee; Angela Sauaia Journal: J Trauma Acute Care Surg Date: 2014-12 Impact factor: 3.313
Authors: I Raza; R Davenport; C Rourke; S Platton; J Manson; C Spoors; S Khan; H D De'Ath; S Allard; D P Hart; K J Pasi; B J Hunt; S Stanworth; P K MacCallum; K Brohi Journal: J Thromb Haemost Date: 2013-02 Impact factor: 5.824