Hunter B Moore1, Ernest E Moore2, Michael P Chapman3, Kirk C Hansen4, Mitchell J Cohen5, Frederic M Pieracci5, James Chandler5, Angela Sauaia6. 1. Department of Surgery, School of Medicine, University of Colorado, Denver, CO. Electronic address: hunter.moore@ucdenver.edu. 2. Department of Surgery, School of Medicine, University of Colorado, Denver, CO; Department of Surgery, Ernest E Moore Shock and Trauma Center at Denver Health, Denver, CO. 3. Department of Surgery, School of Medicine, University of Colorado, Denver, CO. 4. Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado, Denver, CO. 5. Department of Surgery, Ernest E Moore Shock and Trauma Center at Denver Health, Denver, CO. 6. School of Public Health, University of Colorado, Denver, CO; Department of Surgery, Ernest E Moore Shock and Trauma Center at Denver Health, Denver, CO.
Abstract
BACKGROUND: Elevated d-dimers in injured patients with paradoxically low fibrinolysis activity measured by viscoelastic assays have been speculated to be "occult" fibrinolysis. However, an alternative explanation is that these patients have previously activated their fibrinolytic system and have shut it down by the time of blood draw, and would gain no benefit in clot strength with tranexamic acid (TXA). We hypothesize that TXA will not increase clot strength in injured patients with low fibrinolytic activity measured by thrombelastography (TEG), despite biomarkers of fibrinolysis activation. STUDY DESIGN: Three TEG assays (rapid, tissue plasminogen activator, and functional fibrinogen) were run on trauma patients. The tissue plasminogen activator TEG served as a functional assay to quantify depletion of fibrinolysis inhibitors (DFI). Patients were stratified by DFI vs non-DFI and then by rapid TEG lysis at 30 minutes phenotype cutoffs. Response to TXA was evaluated with functional fibrinogen TEG by calculating percent change in clot strength with the addition of exogenous TXA in the TEG cup. RESULTS: Six hundred and thirty patients with a median new injury severity score of 20 were analyzed. Depletion of fibrinolysis inhibitors was present in 116 (18%). The DFI patients had significantly increased d-dimer (p < 0.001) and lower fibrinogen (p < 0.001). The DFI patients had increased rates of massive transfusion (33% vs 3.3%; p < 0.001) and mortality (40% vs 6.2%; p < 0.001). Among DFI patients, TXA significantly improved fibrin clot strength with hyperfibrinolysis (+19% clot strength; p < 0.001) but not with shutdown (+1.2%) or physiologic (-2.5%). CONCLUSIONS: Patients with DFI have multiple abnormalities of their coagulation system, but only DFI patients with hyperfibrinolysis have improved fibrin clot strength with TXA.
BACKGROUND: Elevated d-dimers in injured patients with paradoxically low fibrinolysis activity measured by viscoelastic assays have been speculated to be "occult" fibrinolysis. However, an alternative explanation is that these patients have previously activated their fibrinolytic system and have shut it down by the time of blood draw, and would gain no benefit in clot strength with tranexamic acid (TXA). We hypothesize that TXA will not increase clot strength in injured patients with low fibrinolytic activity measured by thrombelastography (TEG), despite biomarkers of fibrinolysis activation. STUDY DESIGN: Three TEG assays (rapid, tissue plasminogen activator, and functional fibrinogen) were run on traumapatients. The tissue plasminogen activator TEG served as a functional assay to quantify depletion of fibrinolysis inhibitors (DFI). Patients were stratified by DFI vs non-DFI and then by rapid TEG lysis at 30 minutes phenotype cutoffs. Response to TXA was evaluated with functional fibrinogen TEG by calculating percent change in clot strength with the addition of exogenous TXA in the TEG cup. RESULTS: Six hundred and thirty patients with a median new injury severity score of 20 were analyzed. Depletion of fibrinolysis inhibitors was present in 116 (18%). The DFI patients had significantly increased d-dimer (p < 0.001) and lower fibrinogen (p < 0.001). The DFI patients had increased rates of massive transfusion (33% vs 3.3%; p < 0.001) and mortality (40% vs 6.2%; p < 0.001). Among DFI patients, TXA significantly improved fibrin clot strength with hyperfibrinolysis (+19% clot strength; p < 0.001) but not with shutdown (+1.2%) or physiologic (-2.5%). CONCLUSIONS:Patients with DFI have multiple abnormalities of their coagulation system, but only DFI patients with hyperfibrinolysis have improved fibrin clot strength with TXA.
Authors: Christopher D Barrett; Hunter B Moore; Yi-Wen Kong; Michael P Chapman; Ganapathy Sriram; Dan Lim; Ernest E Moore; Michael B Yaffe Journal: J Trauma Acute Care Surg Date: 2019-01 Impact factor: 3.313
Authors: Ernest E Moore; Hunter B Moore; Eduardo Gonzalez; Angela Sauaia; Anirban Banerjee; Christopher C Silliman Journal: Transfusion Date: 2016-04 Impact factor: 3.157
Authors: Jonathan P Meizoso; Charles A Karcutskie; Juliet J Ray; Nicholas Namias; Carl I Schulman; Kenneth G Proctor Journal: J Am Coll Surg Date: 2016-12-23 Impact factor: 6.113
Authors: Jessica C Cardenas; Charles E Wade; Bryan A Cotton; Mitchell J George; John B Holcomb; Martin A Schreiber; Nathan J White Journal: Shock Date: 2019-03 Impact factor: 3.454
Authors: Hunter B Moore; Ernest E Moore; Michael P Chapman; Kevin McVaney; Gary Bryskiewicz; Robert Blechar; Theresa Chin; Clay Cothren Burlew; Fredric Pieracci; F Bernadette West; Courtney D Fleming; Arsen Ghasabyan; James Chandler; Christopher C Silliman; Anirban Banerjee; Angela Sauaia Journal: Lancet Date: 2018-07-20 Impact factor: 79.321
Authors: Hunter B Moore; Hillary Yaffe; James J Pomposelli; Michael Wachs; Thomas Bak; Peter Kennealey; Kendra Conzen; Megan Adams; Thomas Pshak; Rashikh Choudhury; Carson Walker; Alexander Schulick; Tanner Ferrell; Michael P Chapman; Elizabeth A Pomfret; Trevor L Nydam Journal: Am J Surg Date: 2020-08-27 Impact factor: 2.565
Authors: Alexander C Schulick; Hunter B Moore; Carson B Walker; Hillary Yaffe; James J Pomposelli; Fareed Azam; Michael Wachs; Thomas Bak; Peter Kennealey; Kendra Conzen; Megan Adams; Thomas Pshak; Rashikh Choudhury; Michael P Chapman; Elizabeth A Pomfret; Trevor L Nydam Journal: Am J Surg Date: 2020-09-01 Impact factor: 2.565
Authors: Ernest E Moore; Hunter B Moore; Lucy Z Kornblith; Matthew D Neal; Maureane Hoffman; Nicola J Mutch; Herbert Schöchl; Beverley J Hunt; Angela Sauaia Journal: Nat Rev Dis Primers Date: 2021-04-29 Impact factor: 65.038