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Pathophysiology of early trauma-induced coagulopathy: emerging evidence for hemodilution and coagulation factor depletion.

ABSTRACT: Trauma patients present with a coagulopathy, termed early trauma-induced coagulopathy (ETIC), that is associated with increased mortality. This study investigated hemostatic changes responsible for ETIC.Case-control study of trauma patients with and without ETIC, defined as prolonged prothrombin time (PT), was performed from prospective cohort of consecutive trauma patients who presented to Level I trauma center. Univariate and multivariate analyses were performed.The case-control study group (n = 91) was 80% male, with mean age of 37 years, 17% penetrating trauma and 7% mortality rate. Patients with ETIC demonstrated decreased common and extrinsic pathway factor activities (factors V and VII) and decreased inhibition of the coagulation cascade (antithrombin and protein C activities) when compared with the matched control patients without ETIC. Both cohorts had evidence of increased thrombin and fibrin generation (prothrombin fragment 1.2 levels, thrombin-antithrombin complexes, and soluble fibrin monomer), increased fibrinolysis (d-dimer levels), and increased inhibition of fibrinolysis (plasminogen activator inhibitor-1 activity) above normal reference values. Patients with versus without ETIC had increased mortality and received increased amount of blood products.ETIC following injury is associated with decreased factor activities without significant differences in thrombin and fibrin generation, suggesting that despite these perturbations in the coagulation cascade, patients displayed a balanced hemostatic response to injury. The lower factor activities are likely secondary to increased hemodilution and coagulation factor depletion. Thus, decreasing the amount of crystalloid infused in the early phases following trauma and administration of coagulation factors may prevent the development.

SUBMITTER: Shaz BH

PROVIDER: S-EPMC3131448 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Pathophysiology of early trauma-induced coagulopathy: emerging evidence for hemodilution and coagulation factor depletion.

Shaz Beth H BH Winkler Anne M AM James Adelbert B AB Hillyer Christopher D CD MacLeod Jana B JB

The Journal of trauma 20110601 6

<h4>Background</h4>Trauma patients present with a coagulopathy, termed early trauma-induced coagulopathy (ETIC), that is associated with increased mortality. This study investigated hemostatic changes responsible for ETIC.<h4>Methods</h4>Case-control study of trauma patients with and without ETIC, defined as prolonged prothrombin time (PT), was performed from prospective cohort of consecutive trauma patients who presented to Level I trauma center. Univariate and multivariate analyses were perfor ...[more]

PMID: 21460741

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Project description:Background: Traumatic brain injury (TBI)-associated coagulopathy is a widely recognized risk factor for secondary brain damage and contributes to poor clinical outcomes. Various theories, including disseminated intravascular coagulation (DIC), have been proposed regarding its pathomechanisms; no consensus has been reached thus far. This study aimed to elucidate the pathophysiology of TBI-induced coagulopathy by comparing coagulofibrinolytic changes in isolated TBI (iTBI) to those in non-TBI, to determine the associated factors, and identify the clinical significance of DIC diagnosis in patients with iTBI. Methods: This secondary multicenter, prospective study assessed patients with severe trauma. iTBI was defined as Abbreviated Injury Scale (AIS) scores ≥4 in the head and neck, and ≤2 in other body parts. Non-TBI was defined as AIS scores ≥4 in single body parts other than the head and neck, and the absence of AIS scores ≥3 in any other trauma-affected parts. Specific biomarkers for thrombin and plasmin generation, anticoagulation, and fibrinolysis inhibition were measured at the presentation to the emergency department (0 h) and 3 h after arrival. Results: We analyzed 34 iTBI and 40 non-TBI patients. Baseline characteristics, transfusion requirements and in-hospital mortality did not significantly differ between groups. The changes in coagulation/fibrinolysis-related biomarkers were similar. Lactate levels in the iTBI group positively correlated with DIC scores (rho = -0.441, p = 0.017), but not with blood pressure (rho = -0.098, p = 0.614). Multiple logistic regression analyses revealed that the injury severity score was an independent predictor of DIC development in patients with iTBI (odds ratio = 1.237, p = 0.018). Patients with iTBI were further subdivided into two groups: DIC (n = 15) and non-DIC (n = 19) groups. Marked thrombin and plasmin generation were observed in all patients with iTBI, especially those with DIC. Patients with iTBI and DIC had higher requirements for massive transfusion and emergency surgery, and higher in-hospital mortality than those without DIC. Furthermore, DIC development significantly correlated with poor hospital survival; DIC scores at 0 h were predictive of in-hospital mortality. Conclusions: Coagulofibrinolytic changes in iTBI and non-TBI patients were identical, and consistent with the pathophysiology of DIC. DIC diagnosis in the early phase of TBI is key in predicting the outcomes of severe TBI.

Project description:Identifying patients who need damage control resuscitation (DCR) early after trauma is pivotal for adequate management of their critical condition. Several trauma-scoring systems have been developed to identify such patients, but most of them are not simple enough to be used in prehospital settings in the early post-traumatic phase. The Trauma Induced Coagulopathy Clinical Score (TICCS) is an easy-to-measure and strictly clinical trauma score developed to meet this medical need.TICCS is a 3-item clinical score (range: 0 to 18) based on the assessment of general severity, blood pressure and extent of body injury and calculated by paramedics on-site for patients with severe trauma. This non-interventional prospective study was designed to assess the ability of TICCS to discern patients who need DCR. These patients were patients with early acute coagulopathy of trauma (EACT), haemorrhagic shock, massive transfusion and surgical or endovascular haemostasis during hospitalization. Diagnosis of EACT was assessed by both thromboelastometry and conventional coagulation tests.During an 18-month period, 89 severe trauma patients admitted to the general emergency unit at our hospital were enrolled in the study, but 7 were excluded for protocol violations. Of the 82 remaining patients, 8 needed DCR and 74 did not. With receiver operating characteristic curve analysis, TICCS proved to be a powerful discriminant test (area under the curve = 0.98; 95% CI: 0.92 to 1.0). A cutoff of 10 on the TICCS scale provided the best balance between sensitivity (100%; 95% CI: 53.9 to 100) and specificity (95.9%; 95% CI: 88.2 to 99.2). The positive predictive value was 72.7%, and the negative predictive value was 100.0%.TICCS can be easily and rapidly measured by paramedics at the trauma site. In this study of blunt trauma patients, TICCS was able to discriminate between patients with and without need for DCR. TICCS on-site evaluation should allow initiation of optimal care immediately upon hospital admission of patients with severe trauma in need of DCR. However, a larger multicentre prospective study is needed for in-depth validation of TICCS.Clinicaltrials.gov ID: NCT02132208 (registered 6 May 2014).

Project description:INTRODUCTION: We tested two hypotheses that disseminated intravascular coagulation (DIC) and acute coagulopathy of trauma-shock (ACOTS) in the early phase of trauma are similar disease entities and that the DIC score on admission can be used to predict the prognosis of patients with coagulopathy of trauma. METHODS: We conducted a retrospective study of 562 trauma patients, including 338 patients whose data were obtained immediately after admission to the emergency department. We collected serial data for the platelet counts, global markers of coagulation and fibrinolysis, and antithrombin levels. DIC was diagnosed according to the Japanese Association for Acute Medicine (JAAM) DIC scoring system, and ACOTS was defined as a prothrombin-time ratio of >1.2. RESULTS: The higher levels of fibrin/fibrinogen degradation products (FDP) and D-dimer and greater FDP/D-dimer ratios in the DIC patients suggested DIC with the fibrinolytic phenotype. The DIC patients with the fibrinolytic phenotype exhibited persistently lower platelet counts and fibrinogen levels, increased prothrombin time ratios, higher FDP and D-dimer levels, and lower antithrombin levels compared with the non-DIC patients on arrival to the emergency department and during the early stage of trauma. Almost all ACOTS patients met the criteria for a diagnosis of DIC; therefore, the same changes were observed in the platelet counts, global markers of coagulation and fibrinolysis, and antithrombin levels as noted in the DIC patients. The JAAM DIC score obtained immediately after arrival to the emergency department was an independent predictor of massive transfusion and death due to trauma and correlated with the amount of blood transfused. CONCLUSIONS: Patients who develop DIC with the fibrinolytic phenotype during the early stage of trauma exhibit consumption coagulopathy associated with increased fibrin(ogen)olysis and lower levels of antithrombin. The same is true in patients with ACOTS. The JAAM DIC score can be used to predict the prognosis of patients with coagulopathy of trauma.

Dataset Information

Pathophysiology of early trauma-induced coagulopathy: emerging evidence for hemodilution and coagulation factor depletion.

Publications

Pathophysiology of early trauma-induced coagulopathy: emerging evidence for hemodilution and coagulation factor depletion.

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