Acute coagulopathy of trauma: Hypoperfusion induces systemic anticoagulation and hyperfibrinolysis
ABSTRACT Coagulopathy is present at admission in 25% of trauma patients, is associated with shock and a 5-fold increase in mortality. The coagulopathy has recently been associated with systemic activation of the protein C pathway. This study was designed to characterize the thrombotic, coagulant and fibrinolytic derangements of trauma-induced shock.
This was a prospective cohort study of major trauma patients admitted to a single trauma center. Blood was drawn within 10 minutes of arrival for analysis of partial thromboplastin and prothrombin times, prothrombin fragments 1 + 2 (PF1 + 2), fibrinogen, factor VII, thrombomodulin, protein C, plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), tissue plasminogen activator (tPA), and D-dimers. Base deficit was used as a measure of tissue hypoperfusion.
Two hundred eight patients were studied. Systemic hypoperfusion was associated with anticoagulation and hyperfibrinolysis. Coagulation was activated and thrombin generation was related to injury severity, but acidosis did not affect Factor VII or PF1 + 2 levels. Hypoperfusion-induced increase in soluble thrombomodulin levels was associated with reduced fibrinogen utilization, reduction in protein C and an increase in TAFI. Hypoperfusion also resulted in hyperfibrinolysis, with raised tPA and D-Dimers, associated with the observed reduction in PAI-1 and not alterations in TAFI.
Acute coagulopathy of trauma is associated with systemic hypoperfusion and is characterized by anticoagulation and hyperfibrinolysis. There was no evidence of coagulation factor loss or dysfunction at this time point. Soluble thrombomodulin levels correlate with thrombomodulin activity. Thrombin binding to thrombomodulin contributes to hyperfibrinolysis via activated protein C consumption of PAI-1.
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ABSTRACT: Purpose Coagulation changes in pediatric trauma patients are not well defined. To fill this gap, we tested the hypothesis that trauma evokes a hypercoagulable response. Methods A prospective observational study was conducted in hospitalized patients (age 8 months to 14 years) admitted for trauma or elective surgery. Informed consent was obtained from the parents and informed assent was obtained in patients 7 years of age or older. Coagulation changes were evaluated on fresh whole blood using thromboelastography (TEG) and on stored plasma using assays for special clotting factors. Results Forty three patients (22 trauma, median injury severity score = 9; and 21 uninjured controls) were evaluated. With trauma vs control, prothrombin time (PT) was higher by about 10% (p < 0.001), but activated partial thromboplastin time was not altered. TEG clotting time (R; p = 0.005)) and fibrin cross-linking were markedly accelerated (K time, alpha angle; p < 0.001) relative to the control patients. D-Dimer, Prothrombin Fragment 1 + 2, and Plasminogen Activator Inhibitor-1 were all elevated, whereas Protein S activity was reduced (all p < 0.01). Importantly, a large fraction of TEG values and clotting factor assays in the pediatric control group were outside the published reference ranges for adults. Conclusion A hypercoagulable state is associated with minor trauma in children. More work is needed to determine the functional significance of these changes and to establish normal pediatric reference ranges.Journal of Pediatric Surgery 08/2014; 49(8):1295-9. DOI:10.1016/j.jpedsurg.2013.11.050 · 1.31 Impact Factor
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ABSTRACT: Background: Trauma-induced coagulopathy following severe injury is associated with increased bleeding and mortality. Injury may result in alteration of cellular phenotypes and release of cell-derived microparticles (MP). Circulating MPs are procoagulant and support thrombin generation (TG) and clotting. We evaluated MP and TG phenotypes in severely injured patients at admission, in relation to coagulopathy and bleeding. Methods: As part of the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study, research blood samples were obtained from 180 trauma patients requiring transfusions at 5 participating centers. Twenty five healthy controls and 40 minimally injured patients were analyzed for comparisons. Laboratory criteria for coagulopathy was activated partial thromboplastin time (APTT) >= 35 sec. Samples were analyzed by Calibrated Automated Thrombogram to assess TG, and by flow cytometry for MP phenotypes [platelet (PMP), erythrocyte (RMP), leukocyte (LMP), endothelial (EMP), tissue factor (TFMP), and Annexin V positive (AVMP)]. Results: 21.7% of patients were coagulopathic with the median (IQR) APTT of 44 sec (37, 53), and an Injury Severity Score of 26 (17, 35). Compared to controls, patients had elevated EMP, RMP, LMP, and TFMP (all p < 0.001), and enhanced TG (p < 0.0001). However, coagulopathic PROMMTT patients had significantly lower PMP, TFMP, and TG, higher substantial bleeding, and higher mortality compared to non-coagulopathic patients (all p < 0.001). Conclusions: Cellular activation and enhanced TG are predominant after trauma and independent of injury severity. Coagulopathy was associated with lower thrombin peak and rate compared to non-coagulopathic patients, while lower levels of TF-bearing PMPs were associated with substantial bleeding.Thrombosis Research 07/2014; 134(3). DOI:10.1016/j.thromres.2014.07.023 · 2.43 Impact Factor
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ABSTRACT: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are known collectively as venous thromboembolism (VTE). Venous thromboembolic events are common and potentially life-threatening complications following trauma with an incidence of 5 to 63%. DVT prophylaxis is essential in the management of trauma patients. Currently, the optimal VTE prophylaxis strategy for trauma patients is unknown. Traditionally, pelvic and lower extremity fractures, head injury, and prolonged immobilization have been considered risk factors for VTE; however it is unclear which combination of risk factors defines a high-risk group. Modalities available for trauma patient thromboprophylaxis are classified into pharmacologic anticoagulation, mechanical prophylaxis, and inferior vena cava (IVC) filters. The available pharmacologic agents include low-dose heparin (LDH), low molecular weight heparin (LMWH), and factor Xa inhibitors. Mechanical prophylaxis methods include graduated compression stockings (GCSs), pneumatic compression devices (PCDs), and A-V foot pumps. IVCs are traditionally used in high risk patients in whom pharmacological prophylaxis is contraindicated. Both EAST and ACCP guidelines recommend primary use of LMWHs in trauma patients; however there are still controversies regarding the definitive VTE prophylaxis in trauma patients. Large randomized prospective clinical studies would be required to provide level I evidence to define the optimal VTE prophylaxis in trauma patients.05/2011; 2011:505373. DOI:10.1155/2011/505373