Trauma‐induced coagulopathy: The past, present, and future

Abstract

Trauma remains a leading cause of death worldwide, and most early preventable deaths in both the civilian and military settings are due to uncontrolled hemorrhage, despite paradigm advances in modern trauma care. Combined tissue injury and shock result in hemostatic failure, which has been identified as a multidimensional molecular, physiologic and clinical disorder termed trauma-induced coagulopathy (TIC).Understanding the biology of TIC is of utmost importance, as it is often responsible for uncontrolled bleeding, organ failure, thromboembolic complications, and death.Investigations have shown that TIC is characterized by multiple phenotypes of impaired hemostasis due to altered biology in clot formation and breakdown. These coagulopathies are attributable to tissue injury and shock, and encompass underlying endothelial, immune and inflammatory perturbations. Despite the recognition and identification of multiple mechanisms and mediators of TIC, and the development of targeted treatments, the mortality rates and associated morbidities due to hemorrhage after injury remain high. The purpose of this review is to examine the past and present understanding of the multiple distinct but highly integrated pathways implicated in TIC, in order to highlight the current knowledge gaps and future needs in this evolving field, with the aim of reducing morbidity and mortality after injury. K E Y W O R D Sblood coagulation disorders, exsanguination, hemorrhagic shock, hemostasis, trauma | 853 KORNBLITH eT aL.

Defining trauma‐induced coagulopathy with respect to future implications for patient management: Communication from the SSC of the ISTH

“…Trauma‐induced coagulopathy is driven by two distinct and synergistic insults: hypovolemic shock due to blood loss and extensive tissue disruption (Figure ) . The variables that modify the TIC phenotype and course include (a) trauma: injury extent and severity, tissue type injured (head, orthopaedic), degree of hemorrhagic shock, mechanism of injury (blunt, penetrating/hemorrhagic), and time from injury; (b) patient factors: age, sex, medical comorbidities (cardiovascular disease), concomitant anticoagulant use, presence of other toxins including alcohol, heritable differences in baseline coagulation; and (c) resuscitation strategies: types of fluids used, the impact of blood components, adjuncts such as TXA, and timing of surgical intervention . The combination of these three variables distinguishes TIC from the other acute coagulopathies (ie, open cardiovascular surgery, liver transplantation, postpartum hemorrhage, sepsis, malignancy, and autoimmune‐ and toxin‐mediated coagulopathy) .…”

“…The presentation is chiefly thought to be a result of the variability of the magnitude and timing of the interaction between tissue injury and shock as well as resuscitation practices. Variations in experimental measurements such as timing of patient presentation, prior therapy, and timing to blood sampling complicate the definition of TIC …”

“…Variations in experimental measurements such as timing of patient presentation, prior therapy, and timing to blood sampling complicate the definition of TIC. [3][4][5] As a result of the difficulty in defining clinical TIC, the underlying biochemical mechanisms of TIC are unclear. Factors contributing to a hypocoaguable state include impaired thrombin generation, impaired platelet function, deficient or defective fibrinogen, increased fibrinolysis, and endothelial dysfunction, while those contributing to hypercoagulability include excessive thrombin generation, endothelial injury, platelet hyperactivity and exhaustion, hyperfibrinogenemia, and impaired fibrinolysis.…”

Trauma‐induced coagulopathy: The past, present, and future: A comment

“…Previous studies have shown that the main causes of coagulation factor depletion in trauma patients are consumption and capillary leak syndrome due to disseminated intravascular coagulation (DIC), and consumptive thrombohemorrhagic disorder is the main pathophysiology of DIC. 2,3 Table 2 in the original review 1 shows high levels of thrombin-antithrombin III complex (TAT) and prothrombin fragment 1 + 2 (PF1 + 2). These changes reflect the increased thrombin generation, while table 2 shows decreased levels of thrombin.…”

Tranexamic acid for trauma: Repackaged and redelivered

“…Hemorrhage represents the most common cause of preventable death following severe injury, and a rapid response to stop bleeding is essential as exsanguination drives early mortality . Bleeding from injuries can be exacerbated by trauma‐induced coagulopathy, which involves impaired thrombin generation, platelet dysfunction, and altered fibrinolysis . Inhibition of fibrinolysis with tranexamic acid (TXA) in trauma patients at risk of bleeding demonstrates a reduction in mortality when treated within 3 h of injury, while treatment after 3 h increases bleeding risk .…”