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Clinical Management of Major Bleeding and Coagulopathy Following Trauma
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Clinical Management of Major Bleeding and Coagulopathy Following Trauma

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Emergency Medicine".

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 20926

Special Issue Editors

Dr. Petra Innerhofer

E-Mail Website
Guest Editor
Department of Anaesthesiology and Critical Care Medicine, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
Interests: perioperative transfusion therapy; regional anesthesia in pediatric anesthesiology; volume therapy, management of massive blood loss; perioperative coagulation management, traveler's thrombosis
Dr. Dietmar Fries

E-Mail Website
Guest Editor
Department of General and Surgical Intensive Care Medicine, Medical University of Innsbruck, Anichstr. 35, 6020 Innsbruck, Austria
Interests: anaesthesiology; intensive care medicine; critical care medicine; mechanical ventilation anesthesiology; fluid; sepsis; resuscitation

Special Issue Information

Dear Colleagues,

Treatment of patients with severe injury is a worldwide problem and accounts substantially to the global burden of disease. Despite advances in trauma care, the mortality rate is still rather high, even in high-income countries. Recently conducted trauma studies report mortality rates ranging from below 10% to above 30%. The main reasons for early death of these mostly young and otherwise healthy trauma patients are the severity of traumatic brain injury (TBI), followed by death from hemorrhage. Development of multiple-organ failure which strongly correlates with blood loss and the need for massive transfusion contributes to late morbidity and mortality. While reversal of severe TBI is impossible, death from uncontrolled bleeding and MOF is preventable in a substantial proportion of trauma patients. During the past 15 years, we have learned much about the body’s response to injury. The sympathetic–adrenal, coagulation, and complement system are massively activated to maintain circulation, stop blood loss, build up a barrier against invading organisms, and eliminate foreign molecules immediately. However, if clinical management fails to balance the body’s response in a timely manner, an overshoot of induced cascades results in undesirable side effects and poor outcome. Thus, what can we do to improve mortality and morbidity?

This Special Issue, "Clinical Management of Major Bleeding and Coagulopathy Following Trauma", aims to provide an overview of the most important steps in the management of injured patients, thereby reflecting the current knowledge.

Dr. Petra Innerhofer
Dr. Dietmar Fries
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • The European guideline on management of major bleeding and coagulopathy following trauma—what is new?
  • The US perspective on the management of major bleeding
  • Prehospital transfusion, coagulation factor concentrates
  • The value of tranexamic acid, mechanisms, and practical considerations
  • Plasmatic coagulation tests vs. viscoelastic methods
  • Crystalloid or colloid fluids?
  • Formula driven management or goal-directed management
  • Fresh frozen plasma or coagulation factor concentrates for treatment of plasmatic coagulopathy
  • Transfusion thresholds of platelets and effects of platelet transfusion
  • MOF—how to prevent?

Published Papers (6 papers)

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Research

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12 pages, 901 KiB  
Article
First-Line Administration of Fibrinogen Concentrate in the Bleeding Trauma Patient: Searching for Effective Dosages and Optimal Post-Treatment Levels Limiting Massive Transfusion—Further Results of the RETIC Study
by Nicole Innerhofer, Benjamin Treichl, Christopher Rugg, Dietmar Fries, Markus Mittermayr, Tobias Hell, Elgar Oswald, Petra Innerhofer and on behalf of the RETIC Study Group
J. Clin. Med. 2021, 10(17), 3930; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10173930 - 31 Aug 2021
Cited by 7 | Viewed by 2730
Abstract
Fibrinogen supplementation is recommended for treatment of severe trauma hemorrhage. However, required dosages and aimed for post-treatment fibrinogen levels remain a matter of discussion. Within the published RETIC study, adult patients suffering trauma-induced coagulopathy were randomly assigned to receive fibrinogen concentrate (FC) as [...] Read more.
Fibrinogen supplementation is recommended for treatment of severe trauma hemorrhage. However, required dosages and aimed for post-treatment fibrinogen levels remain a matter of discussion. Within the published RETIC study, adult patients suffering trauma-induced coagulopathy were randomly assigned to receive fibrinogen concentrate (FC) as first-line (n = 50) or crossover rescue (n = 20) therapy. Depending on bodyweight, a single dose of 3, 4, 5, or 6 g FC was administered and repeated if necessary (FibA10 < 9 mm). The dose-dependent response (changes in plasma fibrinogen and FibA10) was analyzed. Receiver operating characteristics (ROC) analysis regarding the need for massive transfusion and correlation analyses regarding fibrinogen concentrations and polymerization were performed. Median FC single doses amounted to 62.5 (57 to 66.66) mg.kg−1. One FC single-dose sufficiently corrected fibrinogen and FibA10 (median fibrinogen 213 mg.dL−1, median FibA10 11 mm) only in patients with baseline fibrinogen above 100 mg.dL−1 and FibA10 above 5 mm, repeated dosing was required in patients with lower baseline fibrinogen/FibA10. Fibrinogen increased by 83 or 107 mg.dL−1 and FibA10 by 4 or 4.5 mm after single or double dose of FC, respectively. ROC curve analysis revealed post-treatment fibrinogen levels under 204.5 mg.dL−1 to predict the need for massive transfusion (AUC 0.652; specificity: 0.667; sensitivity: 0.688). Baseline fibrinogen/FibA10 levels should be considered for FC dosing as only sufficiently corrected post-treatment levels limit transfusion requirements. Full article
(This article belongs to the Special Issue Clinical Management of Major Bleeding and Coagulopathy Following Trauma)
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12 pages, 2517 KiB  
Article
The European Perspective on the Management of Acute Major Hemorrhage and Coagulopathy after Trauma: Summary of the 2019 Updated European Guideline
by Marc Maegele
J. Clin. Med. 2021, 10(2), 362; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10020362 - 19 Jan 2021
Cited by 9 | Viewed by 5089
Abstract
Non-controlled hemorrhage with accompanying trauma-induced coagulopathy (TIC) remains the most common cause of preventable death after multiple injury. Rapid identification followed by aggressive treatment is the key for improved outcomes. Treatment of trauma hemorrhage begins at the scene, with manual compression, the use [...] Read more.
Non-controlled hemorrhage with accompanying trauma-induced coagulopathy (TIC) remains the most common cause of preventable death after multiple injury. Rapid identification followed by aggressive treatment is the key for improved outcomes. Treatment of trauma hemorrhage begins at the scene, with manual compression, the use of tourniquets and (non) commercial pelvic slings, and rapid transfer to an adequate trauma center. Upon hospital admission, coagulation monitoring and support are to be initiated immediately. Bleeding is controlled surgically following damage control principles. Modern coagulation management includes goal-oriented, individualized therapies, guided by point-of-care viscoelastic assays. Idarucizumab can be used as an antidote to the thrombin inhibitor dabigatran, andexanet alpha as an antidote to factor Xa inhibitors. This review summarizes the key recommendations of the 2019 updated European guideline on the management of major bleeding and coagulopathy following trauma. These evidence-based recommendations may form the backbone of algorithms adapted to local logistics and infrastructure. Full article
(This article belongs to the Special Issue Clinical Management of Major Bleeding and Coagulopathy Following Trauma)
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14 pages, 1678 KiB  
Article
Sufficient Thrombin Generation Despite 95% Hemodilution: An In Vitro Experimental Study
by Johannes Gratz, Christoph J. Schlimp, Markus Honickel, Nadine Hochhausen, Herbert Schöchl and Oliver Grottke
J. Clin. Med. 2020, 9(12), 3805; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9123805 - 25 Nov 2020
Cited by 13 | Viewed by 1914
Abstract
Guidelines for the treatment of severe bleeding comprise viscoelastic-test-guided use of coagulation factor concentrates as part of their recommendations. The aim of this study is to investigate the effects of substituting fibrinogen, prothrombin complex concentrate, and a combination of both on conventional coagulation [...] Read more.
Guidelines for the treatment of severe bleeding comprise viscoelastic-test-guided use of coagulation factor concentrates as part of their recommendations. The aim of this study is to investigate the effects of substituting fibrinogen, prothrombin complex concentrate, and a combination of both on conventional coagulation tests, viscoelastic test results, and thrombin generation. Blood was drawn from seven healthy volunteers to obtain platelet-free plasma, which later was diluted by replacing 40%, 60%, 80%, 90%, 95%, and 99% with a crystalloid solution. The diluted samples were spiked with fibrinogen concentrate, prothrombin complex concentrate, a combination of both, or a corresponding amount of crystalloid solution. Up to a dilution level of 95%, viscoelastically determined clotting time was significantly shorter in the group substituted with fibrinogen only in comparison with the additional use of prothrombin complex concentrate. Clot firmness and endogenous thrombin potential remained at relatively stable values up to a dilution level of 95% with the substitution of fibrinogen but not prothrombin complex concentrate. Substitution of prothrombin complex concentrate led to an excessive overshoot of thrombin generation. The results of our study question currently propagated treatment algorithms for bleeding patients that include the use of prothrombin complex concentrate for patients without former intake of oral anticoagulants. Even in severely bleeding patients, thrombin generation might be sufficient to achieve adequate hemostasis. Full article
(This article belongs to the Special Issue Clinical Management of Major Bleeding and Coagulopathy Following Trauma)
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15 pages, 2574 KiB  
Article
Dynamics of Platelet Counts in Major Trauma: The Impact of Haemostatic Resuscitation and Effects of Platelet Transfusion—A Sub-Study of the Randomized Controlled RETIC Trial
by Helmuth Tauber, Nicole Innerhofer, Daniel von Langen, Mathias Ströhle, Dietmar Fries, Markus Mittermayr, Tobias Hell, Elgar Oswald and Petra Innerhofer
J. Clin. Med. 2020, 9(8), 2420; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9082420 - 28 Jul 2020
Cited by 5 | Viewed by 2157
Abstract
Although platelets play a central role in haemostasis, the dynamics of platelet counts during haemostatic resuscitation, the response to platelet transfusion, and effects on clinical outcome are poorly described for trauma patients. As a sub-study of the already published randomized controlled RETIC Study [...] Read more.
Although platelets play a central role in haemostasis, the dynamics of platelet counts during haemostatic resuscitation, the response to platelet transfusion, and effects on clinical outcome are poorly described for trauma patients. As a sub-study of the already published randomized controlled RETIC Study “Reversal of Trauma-induced Coagulopathy using First-line Coagulation Factor Concentrates or Fresh-Frozen Plasma” trial, we here analysed whether the type of first-line haemostatic resuscitation influences the frequency of platelet transfusion and determined the effects of platelet transfusion in coagulopathic patients with major trauma. Patients randomly received first-line plasma (FFP) or coagulation factor concentrates (CFC), mainly fibrinogen concentrate. In both groups, platelets were transfused to maintain platelet counts between 50 and 100 × 109/L. Transfusion rates were significantly higher in the FFP (n = 44) vs. CFC (n = 50) group (FFP 47.7% vs. CFC 26%); p = 0.0335. Logistic regression analysis adjusted for the stratification variables injury severity score (ISS) and brain injury confirmed that first-line FFP therapy increases the odds for platelet transfusion (odds ratio (OR) 5.79 (1.89 to 20.62), p = 0.0036) and this effect was larger than a 16-point increase in ISS (OR 4.33 (2.17 to 9.74), p = 0.0001). In conclusion, early fibrinogen supplementation exerted a platelet-saving effect while platelet transfusions did not substantially improve platelet count and might contribute to poor clinical outcome. Full article
(This article belongs to the Special Issue Clinical Management of Major Bleeding and Coagulopathy Following Trauma)
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13 pages, 1671 KiB  
Article
Effects of Circulating HMGB-1 and Histones on Cardiomyocytes–Hemadsorption of These DAMPs as Therapeutic Strategy after Multiple Trauma
by Birte Weber, Ina Lackner, Meike Baur, Giorgio Fois, Florian Gebhard, Ingo Marzi, Hubert Schrezenmeier, Borna Relja and Miriam Kalbitz
J. Clin. Med. 2020, 9(5), 1421; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9051421 - 11 May 2020
Cited by 6 | Viewed by 2498
Abstract
Background and purpose: The aim of the study was to determine the effects of post-traumatically released High Mobility Group Box-1 protein (HMGB1) and extracellular histones on cardiomyocytes (CM). We also evaluated a therapeutic option to capture circulating histones after trauma, using a hemadsorption [...] Read more.
Background and purpose: The aim of the study was to determine the effects of post-traumatically released High Mobility Group Box-1 protein (HMGB1) and extracellular histones on cardiomyocytes (CM). We also evaluated a therapeutic option to capture circulating histones after trauma, using a hemadsorption filter to treat CM dysfunction. Experimental Approach: We evaluated cell viability, calcium handling and mitochondrial respiration of human cardiomyocytes in the presence of HMGB-1 and extracellular histones. In a translational approach, a hemadsorption filter was applied to either directly eliminate extracellular histones or to remove them from blood samples obtained from multiple injured patients. Key results: Incubation of human CM with HMGB-1 or histones is associated with changes in calcium handling, a reduction of cell viability and a substantial reduction of the mitochondrial respiratory capacity. Filtrating plasma from injured patients with a hemadsorption filter reduces histone concentration ex vivo and in vitro, depending on dosage. Conclusion and implications: Danger associated molecular patterns such as HMGB-1 and extracellular histones impair human CM in vitro. A hemadsorption filter could be a therapeutic option to reduce high concentrations of histones. Full article
(This article belongs to the Special Issue Clinical Management of Major Bleeding and Coagulopathy Following Trauma)
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Review

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16 pages, 312 KiB  
Review
Whole Blood, Fixed Ratio, or Goal-Directed Blood Component Therapy for the Initial Resuscitation of Severely Hemorrhaging Trauma Patients: A Narrative Review
by Mark Walsh, Ernest E. Moore, Hunter B. Moore, Scott Thomas, Hau C. Kwaan, Jacob Speybroeck, Mathew Marsee, Connor M. Bunch, John Stillson, Anthony V. Thomas, Annie Grisoli, John Aversa, Daniel Fulkerson, Stefani Vande Lune, Lucas Sjeklocha and Quincy K. Tran
J. Clin. Med. 2021, 10(2), 320; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10020320 - 17 Jan 2021
Cited by 19 | Viewed by 5392
Abstract
This narrative review explores the pathophysiology, geographic variation, and historical developments underlying the selection of fixed ratio versus whole blood resuscitation for hemorrhaging trauma patients. We also detail a physiologically driven and goal-directed alternative to fixed ratio and whole blood, whereby viscoelastic testing [...] Read more.
This narrative review explores the pathophysiology, geographic variation, and historical developments underlying the selection of fixed ratio versus whole blood resuscitation for hemorrhaging trauma patients. We also detail a physiologically driven and goal-directed alternative to fixed ratio and whole blood, whereby viscoelastic testing guides the administration of blood components and factor concentrates to the severely bleeding trauma patient. The major studies of each resuscitation method are highlighted, and upcoming comparative trials are detailed. Full article
(This article belongs to the Special Issue Clinical Management of Major Bleeding and Coagulopathy Following Trauma)
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