Severe Trauma-Induced Coagulopathy: Molecular Mechanisms Underlying Critical Illness

Abstract

Trauma remains one of the leading causes of death in adults despite the implementation of preventive measures and innovations in trauma systems. The etiology of coagulopathy in trauma patients is multifactorial and related to the kind of injury and nature of resuscitation. Trauma-induced coagulopathy (TIC) is a biochemical response involving dysregulated coagulation, altered fibrinolysis, systemic endothelial dysfunction, platelet dysfunction, and inflammatory responses due to trauma. The aim of this review is to report the pathophysiology, early diagnosis and treatment of TIC. A literature search was performed using different databases to identify relevant studies in indexed scientific journals. We reviewed the main pathophysiological mechanisms involved in the early development of TIC. Diagnostic methods have also been reported which allow early targeted therapy with pharmaceutical hemostatic agents such as TEG-based goal-directed resuscitation and fibrinolysis management. TIC is a result of a complex interaction between different pathophysiological processes. New evidence in the field of trauma immunology can, in part, help explain the intricacy of the processes that occur after trauma. However, although our knowledge of TIC has grown, improving outcomes for trauma patients, many questions still need to be answered by ongoing studies.

Keywords: blood coagulation disorders; exsanguination; hemorrhagic shock; hemostasis; polytrauma physiology; trauma.

Figure 1

The interplay between metabolic acidosis, hypothermia and progressive coagulopathy in trauma.

Figure 2

Virchow’s triad that interfere with the clinical course.

Chart 1

Included and excluded articles.

Figure 3

Qualitative changes in coagulation parameters in trauma-induced coagulopathy. Tissue injury and shock ① synergistically activate the endothelium, platelets and the immune system ② to generate an array of mediators that reduce fibrinogen, impair platelet function and compromise thrombin generation ③, ultimately resulting in inadequate clot formation for hemostasis ④. Increased fibrinolysis via plasmin generation further compromises hemostatic capacity. These deficits are accentuated by ongoing blood loss, hemodilution, metabolic acidosis and hypothermia. A colour gradient indicates that the mechanism can result in both hypocoagulation (green) and hypercoagulation (yellow). DAMPs, damage-associated molecular patterns; HMGB1, high mobility group protein B1; PAI-1, plasminogen activator inhibitor-1; tPA, tissue plasminogen factor [62].

Figure 4

TEG (thromboelastography) and ROTEM (rotational thromboelastometry).

Figure 5

Subsequent management of trauma-induced coagulopathy. Abbreviations: ACT, activated clotting time; aPTT, activated partial thromboplastin time; CCA, conventional coagulation assay; LY30, percentage reduction in the area under the curve at 30 min after MA in TEG; MA, maximum amplitude; PT, prothrombin time; RBC, red blood cell; SBP, systolic blood pressure; VHA, viscoelastic hemostatic assay.