Literature DB >> 29664836

TEG Lysis Shutdown Represents Coagulopathy in Bleeding Trauma Patients: Analysis of the PROPPR Cohort.

Jessica C Cardenas1,2, Charles E Wade1,2, Bryan A Cotton1,2, Mitchell J George1, John B Holcomb1,2, Martin A Schreiber3, Nathan J White4.   

Abstract

BACKGROUND: Thrombelastography (TEG) fibrinolysis shutdown after trauma is associated with increased mortality due to hypercoagulability-associated organ failure. However, a lack of mechanistic data has precluded the development of novel interventions to treat shutdown.
OBJECTIVES: To define the pathophysiology of TEG shutdown in severely injured, bleeding patients through secondary analysis of the PROPPR trial.
METHODS: Fibrinolysis was characterized in PROPPR subjects using admission TEG lysis at 30 min (LY30) or plasmin-antiplasmin (PAP) levels. LY30 categories were low (<0.9%), moderate (0.9-2.9%), or high (≥ 3%). PAP was classified as low (<1,500 μg/L), moderate (1,500-20,000 μg/L), or high (>20,000 μg/L). Demographics, outcomes, admission TEG values, platelet count and function, standard coagulation tests, and coagulation proteins were compared.
RESULTS: Five hundred forty-seven patients had TEG data and 549 patients had PAP data available. Low LY30 was associated with reduced platelet count and aggregation, poorer TEG clot formation, prolonged clotting times, and reduced fibrinogen and alpha2 antiplasmin. Compared to moderate PAP, low PAP subjects had similar platelet parameters, TEG values, fibrinogen, and alpha2 antiplasmin, but reduced tPA, and elevated PAI-1. D-Dimer values increased as PAP increased, however patients with low LY30 had elevated D-Dimer compared with moderate LY30 patients. Most low LY30 deaths were due to TBI (45%) and hemorrhage (42%) versus one of each cause (TBI, hemorrhage, MOF) in low PAP patients.
CONCLUSIONS: Low TEG LY30 does not reflect shutdown of enzymatic fibrinolysis with hypercoagulability, but rather a coagulopathic state of moderate fibrinolysis with fibrinogen consumption and platelet dysfunction that is associated with poor outcomes.

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Year:  2019        PMID: 29664836      PMCID: PMC6191375          DOI: 10.1097/SHK.0000000000001160

Source DB:  PubMed          Journal:  Shock        ISSN: 1073-2322            Impact factor:   3.454


  14 in total

1.  The effects of platelet count on clot retraction and tissue plasminogen activator-induced fibrinolysis on thrombelastography.

Authors:  Nobuyuki Katori; Kenichi A Tanaka; Fania Szlam; Jerrold H Levy
Journal:  Anesth Analg       Date:  2005-06       Impact factor: 5.108

2.  Fibrinolytic shutdown: fascinating theory but randomized controlled trial data are needed.

Authors:  Ian Roberts
Journal:  Transfusion       Date:  2016-04       Impact factor: 3.157

3.  Acute Fibrinolysis Shutdown after Injury Occurs Frequently and Increases Mortality: A Multicenter Evaluation of 2,540 Severely Injured Patients.

Authors:  Hunter B Moore; Ernest E Moore; Ioannis N Liras; Eduardo Gonzalez; John A Harvin; John B Holcomb; Angela Sauaia; Bryan A Cotton
Journal:  J Am Coll Surg       Date:  2016-01-22       Impact factor: 6.113

4.  The hyperfibrinolytic phenotype is the most lethal and resource intense presentation of fibrinolysis in massive transfusion patients.

Authors:  John R Taylor; Erin E Fox; John B Holcomb; Sandro Rizoli; Kenji Inaba; Martin A Schreiber; Karen Brasel; Thomas M Scalea; Charles E Wade; Eileen Bulger; Bryan A Cotton
Journal:  J Trauma Acute Care Surg       Date:  2018-01       Impact factor: 3.313

5.  Persistent Fibrinolysis Shutdown Is Associated with Increased Mortality in Severely Injured Trauma Patients.

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

6.  Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) Trial: design, rationale and implementation.

Authors:  Sarah Baraniuk; Barbara C Tilley; Deborah J del Junco; Erin E Fox; Gerald van Belle; Charles E Wade; Jeanette M Podbielski; Angela M Beeler; John R Hess; Eileen M Bulger; Martin A Schreiber; Kenji Inaba; Timothy C Fabian; Jeffrey D Kerby; Mitchell Jay Cohen; Christopher N Miller; Sandro Rizoli; Thomas M Scalea; Terence O'Keeffe; Karen J Brasel; Bryan A Cotton; Peter Muskat; John B Holcomb
Journal:  Injury       Date:  2014-06-10       Impact factor: 2.586

7.  Viscoelastic measurements of platelet function, not fibrinogen function, predicts sensitivity to tissue-type plasminogen activator in trauma patients.

Authors:  H B Moore; E E Moore; M P Chapman; E Gonzalez; A L Slaughter; A P Morton; A D'Alessandro; K C Hansen; A Sauaia; A Banerjee; C C Silliman
Journal:  J Thromb Haemost       Date:  2015-09-22       Impact factor: 5.824

8.  Hyperfibrinolysis, physiologic fibrinolysis, and fibrinolysis shutdown: the spectrum of postinjury fibrinolysis and relevance to antifibrinolytic therapy.

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

9.  Elevated tissue plasminogen activator and reduced plasminogen activator inhibitor promote hyperfibrinolysis in trauma patients.

Authors:  Jessica C Cardenas; Nena Matijevic; Lisa A Baer; John B Holcomb; Bryan A Cotton; Charles E Wade
Journal:  Shock       Date:  2014-06       Impact factor: 3.454

10.  Overwhelming tPA release, not PAI-1 degradation, is responsible for hyperfibrinolysis in severely injured trauma patients.

Authors:  Michael P Chapman; Ernest E Moore; Hunter B Moore; Eduardo Gonzalez; Fabia Gamboni; James G Chandler; Sanchayita Mitra; Arsen Ghasabyan; Theresa L Chin; Angela Sauaia; Anirban Banerjee; Christopher C Silliman
Journal:  J Trauma Acute Care Surg       Date:  2016-01       Impact factor: 3.313

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  17 in total

Review 1.  Fibrinolysis Shutdown in Trauma: Historical Review and Clinical Implications.

Authors:  Hunter B Moore; Ernest E Moore; Matthew D Neal; Forest R Sheppard; Lucy Z Kornblith; Dominik F Draxler; Mark Walsh; Robert L Medcalf; Mitch J Cohen; Bryan A Cotton; Scott G Thomas; Christine M Leeper; Barbara A Gaines; Angela Sauaia
Journal:  Anesth Analg       Date:  2019-09       Impact factor: 5.108

2.  Does Tranexamic Acid Improve Clot Strength in Severely Injured Patients Who Have Elevated Fibrin Degradation Products and Low Fibrinolytic Activity, Measured by Thrombelastography?

Authors:  Hunter B Moore; Ernest E Moore; Michael P Chapman; Kirk C Hansen; Mitchell J Cohen; Frederic M Pieracci; James Chandler; Angela Sauaia
Journal:  J Am Coll Surg       Date:  2019-03-29       Impact factor: 6.113

3.  What's New in Shock, March 2019?

Authors:  Hongkuan Fan; Andrew J Goodwin
Journal:  Shock       Date:  2019-03       Impact factor: 3.454

Review 4.  Novel blood derived hemostatic agents for bleeding therapy and prophylaxis.

Authors:  Shailaja Hegde; Yi Zheng; Jose A Cancelas
Journal:  Curr Opin Hematol       Date:  2022-08-03       Impact factor: 3.218

5.  Proteomics of Coagulopathy Following Injury Reveals Limitations of Using Laboratory Assessment to Define Trauma-Induced Coagulopathy to Predict Massive Transfusion.

Authors:  Hunter B Moore; Matthew D Neal; Marnie Bertolet; Brian A Joughin; Michael B Yaffe; Christopher D Barrett; Molly A Bird; Russell P Tracy; Ernest E Moore; Jason L Sperry; Brian S Zuckerbraun; Myung S Park; Mitchell J Cohen; Stephen R Wisniewski; James H Morrissey
Journal:  Ann Surg Open       Date:  2022-05-25

6.  Endotheliopathy is Associated with a 24-hour Fibrinolysis Phenotype Described by Low TEG Lysis and High D-Dimer after Trauma: a Secondary Analysis of the PROPPR Study.

Authors:  Robert P Richter; Danielle M Joiner; Russell L Griffin; Jan O Jansen; Jeffrey D Kerby; Charles E Wade; John B Holcomb; Jessica C Cardenas; Jillian R Richter
Journal:  Ann Surg Open       Date:  2022-03

7.  Effects of pathogen reduction technology and storage duration on the ability of cryoprecipitate to rescue induced coagulopathies in vitro.

Authors:  Kimberly A Thomas; Susan M Shea; Philip C Spinella
Journal:  Transfusion       Date:  2021-03-23       Impact factor: 3.157

8.  Dense and dangerous: The tissue plasminogen activator-resistant fibrinolysis shutdown phenotype is due to abnormal fibrin polymerization.

Authors:  Nathan Dow; Julia R Coleman; Hunter Moore; Zachary T Osborn; Adrian M Sackheim; Grant Hennig; Saulius Butenas; Mark T Nelson; Ernest E Moore; Kalev Freeman
Journal:  J Trauma Acute Care Surg       Date:  2020-02       Impact factor: 3.697

Review 9.  Trauma-induced coagulopathy.

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

10.  Pathologic Fibrinolysis is More Common in a Rural Trauma Setting.

Authors:  James M Bardes; Daniel J Grabo; Sijin Wen; Alison Wilson
Journal:  Am Surg       Date:  2020-12-15       Impact factor: 1.002

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