1 / 26

EE Moore Denver Health / University of Colorado Denver

Explore mortality patterns in trauma patients based on fibrinolysis phenotypes and the potential mechanisms involved. Understand the impact of hyperfibrinolysis and shutdown on patient outcomes. This study delves into factors contributing to mortality post-injury and the role of various components in coagulopathy.

cburman
Download Presentation

EE Moore Denver Health / University of Colorado Denver

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. EE Moore Denver Health / University of Colorado Denver Disclosure : Haemonetics & TEM Research Support

  2. 20,211 Adult : SBP < 90 or HR > 110 within 8 Hr Mortality : 14.5% vs 16.0% ( p < .04) Death due to Bleeding : 4.9% vs 5.7% ( p < .08 ) Blood Transfusion … Only 50% of Patients No Reduction in Transfusion ( ~ 6 Units RBC ) CRASH-2 Trial : RCT / 274 Hospitals / 40 Countries Lancet 2010

  3. CRASH-2 Trial : RCT / 274 Hospitals / 40 Countries Relative Risk < 1 hr = 0.68 1 - 3 hr = 0.70 > 3 hr = 1.44 Lancet 2011

  4. TIC : Factor Depletion vs Fibrinolysis Surgery 2014

  5. Shock Enhances Fibrinolysis …Tissue Injury Inhibits Fibrinolysis

  6. Trauma Study Population • 193 patients 70% male, Age 44 • Median ISS 29 ( IQR 22-36 ) • Median BD 9 ( IQR 6-13 ) • 21% Mortality

  7. Postinjury Spectrum of Fibrinolysis N=156 ( 71% ) N=37 ( 19% ) N=123 ( 64% ) N=33 ( 17% ) Microvascular Occlusion Uncontrolled Bleeding Vascular Patency Mortality = 19 ( 58% ) Mortality = 20 ( 16% ) Mortality = 1 ( 3% )

  8. Clinical Outcomes : Fibrinolysis J Trauma 2014

  9. Fibrinolysis Phenoype : Mortality

  10. Hyperfibrinolysis = PAI-1 Depletion

  11. Fibrinolysis Shutdown = Excessive PAI-1

  12. TPA Challenge TPA Non PAI-1 Inhibition TPA Levels ? ? tPA Augmentation ? tPAComplexed % LY30

  13. Fibrinogen Fibrin Degradation Products Direct tPA Inhibition Sc-tPA PAI-1 Direct Plasmin Inhibition Fibrinolysis Alpha 2 Macroglobulin ? Fibrin Level Inhibition TAFI Alpha 2 Anti-plasmin Cross linking (factor XIII) Granule (Alpha, Dense) Platelet Fibrin Polymer Plasminogen and sc-tPA Converted Plasmin and tc-tPA

  14. Potential Mechanisms For Phenotypes • Red Blood Cell Degradation in Major Trauma Proteomics: Shock Wohlauer et al 2010 Metabolomics: J Metabolomics D’alessandro In press • Platelet Transfusion Associated with MOF • Granules contain anti-fibrinolytics

  15. Study Methods • Citrated Volunteers Whole Blood • % replaced with Lysed • Own RBCs • Donor Platelets • Leukoreduced RBCS • tPA TEG Challenge • Exogenous tPA mixed with blood • Run on TEG • 75ng/ml final concentration • Ly30: Lysis at 30 min used for assessment of fibrinolysis

  16. Lysed RBCs Enhance tPA Mediated Fibrinolysis at a Low Dose

  17. Lysed Platelets Shutdown Fibrinolysis at a Low Dose

  18. Credits : UCD Trauma Research Team Ani Banerjee Kirk Hansen Angela Sauaia Chris Silliman Carl Barnett Denis Bensrad Walt Biffl Clay Burlew Chuck Fox Jerry Jurkovich Fred Pieracci Rob Stoval Sarah Ammons Jim Chandler Andrea Emard Cortney Fleming Arsen Ghasabyan Ray Shepard-Singh Mike Chapman Theresa Chin Eduardo Gonzalez Hunter Moore Max Wohlauer NIH P50 GM 4922 NIH T32 GM 08315 NIH UM1 HL 129877

  19. X VIII / vWF TF Xa IIa Va VIIa VIIIa TF-Bearing Cell TF V Va VIIa IX Platelet IXa II X IXa Xa IIa VIIIa Va Activated Platelet VIIa IXa Va IX IIa Xa VIIIa II X Thank you !!!

  20. Hyperfibrinolysis : Early MortalityShutdown : Delayed Mortality Shutdown Hyperfibrinolysis

  21. Tissue Factor Thrombin Hypoxia Tissue Injury Histones Elastase HMGB1 Complement Genetics Co –Morbidity Medication Adrenaline Postinjury Hyperfibrinolysis sThrombomodulin Heparan Sulfate sCD40L Endothelial Dysfunction • Acidosis • Hypothermia • Dilution • Consumption Activated Protein C tPA Plasmin ? PAI-1 FXIIIa FibrinolysiS TRAUMA INDUCED COAGULOPATHY

  22. TIC : Principal Component Analysis Kutcher, Cohen et al J Trauma 2013

  23. Blood Component Transfusion

  24. Incidence of Postinjury Fibrinolysis • Denver=2% Activations ( 17 % M Transfusion ) • Houston= 2% Activations • Lyon = 6% Activations • Salzburg = 8% Activations • Los Angeles = ( 10% M Transfusion ) • San Francisco = ( 20% M Transfusion )

  25. Recent Trauma Experience in the US J Trauma 2014

More Related