Kushimoto et al. Journal of Intensive Care (2017) 5:6 DOI 10.1186/s40560-016-0196-6 REVIEW Open Access Acute traumatic coagulopathy and trauma- induced coagulopathy: an overview Shigeki Kushimoto1,2* , Daisuke Kudo1,2 and Yu Kawazoe1,2 Abstract Hemorrhage is the most important contributing factor of acute-phase mortality in trauma patients. Previously, traumatologists and investigators identified iatrogenic and resuscitation-associated causes of coagulopathic bleeding after traumatic injury, including hypothermia, metabolic acidosis, and dilutional coagulopathy that were recognized as primary drivers of bleeding after trauma. However, the last 10 years has seen a widespread paradigm shift in the resuscitation of critically injured patients, and there has been a dramatic evolution in our understanding of trauma-induced coagulopathy. Although there is no consensus regarding a definition or an approach to the classification and naming of trauma-associated coagulation impairment, trauma itself and/or traumatic shock- induced endogenous coagulopathy are both referred to as acute traumatic coagulopathy (ATC), and multifactorial trauma-associated coagulation impairment, including ATC and resuscitation-associated coagulopathy is recognized as trauma-induced coagulopathy. Understanding the pathophysiology of trauma-induced coagulopathy is vitally important, especially with respect to the critical issue of establishing therapeutic strategies for the management of patients with severe trauma. Keywords: Acute traumatic coagulopathy, Trauma-induced coagulopathy, Disseminated intravascular coagulation Background metabolic failure than from the failure to complete Trauma remains a leading cause of death and permanent organ repairs [7, 8]. Coagulopathy is one of the most disability in adults despite advances in systematic ap- preventable causes of death in trauma and has been proaches including prevention, resuscitation, surgical implicated as the cause of almost half of hemorrhagic management, and critical care [1]. Trauma-related death deaths in trauma patients [8, 9]. and disability have also been suggested to have a great Previous landmark studies identified iatrogenic and impact on global productivity. resuscitation-associated causes of coagulopathic bleeding Bleeding accounts for 30–40% of all trauma-related after traumatic injury, of which hypothermia, metabolic deaths and typically occurs within hours after injury [2]. acidosis, and dilutional coagulopathy were recognized as Although the mortality of trauma patients requiring primary drivers of bleeding after trauma [9–11]. How- massive transfusion exceeds 50% [3], at least 10% of ever, endogenous acute coagulopathy, which occurs deaths after traumatic injury are potentially preventable, within minutes following injury, before and independent and 15% of those are due to hemorrhage; many of these of iatrogenic factors, is clearly recognized and accepted deaths occur within the first few hours of definitive care, as the primary cause of perturbed coagulation after in- with coagulopathy playing a crucial role [4–6]. jury [12]. Coagulopathy is present at the time of admis- Regarding the management of patients requiring sion to the emergency department in up to 25–35% of massive transfusion, it has been repeatedly suggested trauma patients [9, 10, 13]. Understanding the patho- that patients are more likely to die from intraoperative physiology of trauma-induced coagulopathy is vitally important, especially with respect to the critical issue of * Correspondence: [email protected] establishing therapeutic strategies for the management 1 Division of Emergency and Critical Care Medicine, Tohoku University of patients with severe trauma [14]. Graduate School of Medicine, Seiryo-machi 2-1, Aoba-ku, Sendai, Miyagi 980-8574, Japan 2Department of Emergency and Critical Care Medicine, Tohoku University Hospital, Seiryo-machi 1-1, Aoba-ku, Sendai, Miyagi 980-8574, Japan © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Kushimoto et al. Journal of Intensive Care (2017) 5:6 Page 2 of 7 Coagulopathy in the acute phase of trauma: not a simple classification and naming of trauma-associated coagula- dilutional and resuscitation-related coagulopathy tion impairment, in this manuscript, we define ATC as Coagulopathy in the acute phase of trauma has long trauma itself (directly trauma-induced) and/or traumatic been known to coexist with severe hemorrhage and has shock-induced endogenous ATC and trauma-induced been recognized as a co-phenomenon and unavoidable coagulopathy as multifactorial trauma-associated coagula- sequela of resuscitation for patients requiring massive tion impairment, including ATC and resuscitation- transfusion, and accompanied by hypothermia, meta- associated coagulopathy associated with hypothermia, bolic acidosis, and dilutional coagulopathy. However, our metabolic acidosis, and dilutional coagulopathy [11, 18]. understanding of the mechanisms and clinical import- Gando and Hayakawa summarized the important compo- ance of coagulopathy changed significantly after the nents of trauma-induced coagulopathy, consisting of identification of an endogenous coagulation abnormality, endogenously (trauma- and traumatic shock-induced) i.e., acute traumatic coagulopathy (ATC), nearly a decade primary pathologies and exogenous secondary pathologies ago [9, 10]. The presence of this impairment early after (Table 1) [21]. trauma has been demonstrated to be an independent Cap and Hunt classified trauma-associated coagulopa- predictor for increased organ dysfunction, infection, and thies into three phases [11]. The first phase is immediate overall mortality [15]. Trauma itself and/or traumatic activation of multiple hemostatic pathways, with increased shock can directly induce endogenous ATC, in contrast fibrinolysis, in association with tissue injury and/or tissue with the indirect mechanisms such as hypothermia, hypoperfusion. The second phase involves therapy-related metabolic acidosis, and dilutional coagulopathy [16–18]. factors during resuscitation. The third, post-resuscitation, These contributing factors of hemostatic impairment phase is an acute-phase response leading to a prothrom- exacerbate ATC and may participate collectively to the botic state predisposing to venous thromboembolism. clinical features of trauma-induced coagulopathy [16–18]. Of these three phases, the first phase corresponds to Acute coagulopathy has recently been identified at admis- ATC, and the clinical features of the first phase along with sion before trauma resuscitation in one in four trauma the pathophysiologic factors of the second phase provide patients [10, 13, 19], and is associated with a fourfold in- the characteristics of trauma-induced coagulopathy (Fig. 2) crease in mortality [9, 10, 13, 19]. [22]. Recently, the clinical features and pathophysiology of Coagulopathy in the acute phase of trauma patients trauma-induced coagulopathy have been recognized as the consists of two core components: (1) trauma itself and/ comprehensive condition of ATC involving resuscitation- or traumatic shock-induced endogenous ATC and (2) associated coagulopathy, a systemic inflammatory re- resuscitation-associated coagulopathy [20] (Fig. 1). sponse to tissue injury, and predisposing factors [23]. Although no consensus has been reached regarding a Currently recommended management lists for the first definition and there are different approaches to the and second phases based on The European guideline on management of major bleeding and coagulopathy are summarized as Table 2 [24]. It is also recom- mended that early mechanical thromboprophylaxis Table 1 Summary of trauma-induced coagulopathy (cited from [21]) 1 Physiological changes • Hemostasis and wound healing 2 Pathological changes • Endogenously induced primary pathologies o Disseminated intravascular coagulation (DIC) • Activation of coagulation • Insufficient anticoagulation mechanisms • Increased fibrin(ogen)olysis (early phase) • Suppression of fibrinolysis (late phase) • Consumption coagulopathy Fig. 1 Time phase of two components of trauma-induced o Acute coagulopathy trauma-shock (ACOTS) coagulopathy following injury: acute traumatic coagulopathy • Activated protein C-mediated suppression of coagulation (ATC) and resuscitation-associated coagulopathy. Endogenous • Activated protein C-mediated increased fibrinolysis • ATC caused by trauma itself and traumatic shock presents imme- Exogenously induced secondary pathologies that modify DIC diately after injury and continue during resuscitation phase. and ACOTS o Anemia-induced coagulopathy Resuscitation-associated coagulopathy, involving hypothermia, o Hypothermia-induced coagulopathy metabolic acidosis, and dilutional coagulopathy, aggravates the o Acidosis-induced coagulopathy ATC accompanied with therapeutic resuscitation and continue to o Dilutional coagulopathy post-resuscitation phase o Others Kushimoto et al. Journal of Intensive Care