Early traumatic coagulopathy occurs only in the presence of tissue hypoperfusion and appears to occur without significant consumption of coagulation factors. Alterations in the thrombomodulin-protein C pathway are consistent with activated protein C activation and systemic anticoagulation. Admission plasma thrombomodulin and protein C levels are predictive of clinical outcomes following major trauma.

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.

Perioperative monitoring of blood coagulation is critical to better understand causes of hemorrhage, to guide hemostatic therapies, and to predict the risk of bleeding during the consecutive anesthetic or surgical procedures. Point-of-care (POC) coagulation monitoring devices assessing the viscoelastic properties of whole blood, i.e., thrombelastography, rotation thrombelastometry, and Sonoclot analysis, may overcome several limitations of routine coagulation tests in the perioperative setting. The advantage of these techniques is that they have the potential to measure the clotting process, starting with fibrin formation and continue through to clot retraction and fibrinolysis at the bedside, with minimal delays. Furthermore, the coagulation status of patients is assessed in whole blood, allowing the plasmatic coagulation system to interact with platelets and red cells, and thereby providing useful additional information on platelet function. Viscoelastic POC coagulation devices are increasingly being used in clinical practice, especially in the management of patients undergoing cardiac and liver surgery. Furthermore, they provide useful information in a large variety of clinical scenarios, e.g., massive hemorrhage, assessment of hypo- and hypercoagulable states, guiding pro- and anticoagulant therapies, and in diagnosing of a surgical bleeding. A surgical etiology of bleeding has to be considered when viscoelastic test results are normal. In summary, viscoelastic POC coagulation devices may help identify the cause of bleeding and guide pro- and anticoagulant therapies. To ensure optimal accuracy and performance, standardized procedures for blood sampling and handling, strict quality controls and trained personnel are required.

TBI alone does not cause early coagulopathy, but must be coupled with hypoperfusion to lead to coagulation derangements, associated with the activation of the protein C pathway. This novel finding has significant implications for the treatment of coagulopathy after severe brain injury.

Complement activation has been reported after major trauma. However, little is known about the clinical relevance and the mechanisms of complement activation early after trauma. Therefore, the aim of this study was to measure complement activation, to identify the roles of injury severity and hypoperfusion, to determine the predominant activated pathway, and to identify the clinical significance of early complement activation in trauma patients. A total of 208 adult trauma patients were enrolled in this prospective single-center cohort study of major trauma patients. Blood samples were obtained within 30 min after injury before any significant fluid resuscitation. Complement (C5b-9) was activated early after trauma, correlated with injury severity and tissue hypoperfusion, and was associated with increased mortality rate and with the development of organ failure such as acute lung injury and acute renal failure. The alternative pathway seems to be the predominant activated complement pathway early after trauma. However, the classical and/or the lectin pathway initiated complement activation because of the correlation between plasma levels of C4d and C3a/C5b-9. Finally, in patients with low C3a levels, C5b-9 levels correlated with plasma levels of prothrombin fragments 1 + 2, a marker of thrombin generation, suggesting additional C3-independent complement activation by thrombin after severe trauma. In summary, complement activation via its amplification by the alternative pathway is observed early after trauma and correlates with injury severity, tissue hypoperfusion, and worse clinical outcomes. Besides complement activation by the classical and/or lectin pathways, there is an independent association between thrombin generation and complement activation.

Abstract-Interleukin (IL)-1␤ has previously been shown to be among the most biologically active cytokines in the lungs of patients with acute lung injury (ALI). Furthermore, there is experimental evidence that lung vascular permeability increases after short-term exposure to IL-1 protein, although the exact mechanism is unknown. Therefore, the objective of this study was to determine the mechanisms of IL-1␤-mediated increase in lung vascular permeability and pulmonary edema following transient overexpression of this cytokine in the lungs by adenoviral gene transfer. Lung vascular permeability increased with intrapulmonary IL-1␤ production with a maximal effect 7 days after instillation of the adenovirus. Furthermore, inhibition of the ␣v␤6 integrin and/or transforming growth factor-␤ attenuated the IL-1␤-induced ALI. The results of in vitro studies indicated that IL-1␤ caused the activation of transforming growth factor-␤ via RhoA/␣v␤6 integrin-dependent mechanisms and the inhibition of the ␣v␤6 integrin and/or transforming growth factor-␤ signaling completely blocked the IL-1␤-mediated protein permeability across alveolar epithelial cell monolayers. In addition, IL-1␤ increased protein permeability across lung endothelial cell monolayers via RhoA-and ␣v␤5 integrin-dependent mechanisms. The final series of in vivo experiments demonstrated that pretreatment with blocking antibodies to both the ␣v␤5 and ␣v␤6 integrins had an additive protective effect against IL-1␤-induced ALI. In summary, these results demonstrate a critical role for the ␣v␤5/␤6 integrins in mediating the IL-1␤-induced ALI and indicate that these integrins could be a potentially attractive therapeutic target in ALI. Key Words: lung Ⅲ cytokines Ⅲ inflammation Ⅲ endothelial cells Ⅲ epithelial cells Ⅲ rodents A cute lung injury (ALI) is a devastating clinical syndrome in critically ill patients with an overall mortality rate of 30% to 40%. 1 The syndrome is characterized by alveolar epithelial and lung endothelial injury leading to increased permeability across the alveolar-capillary barrier, pulmonary edema, and acute respiratory failure. 2 Despite an improved understanding of the pathogenesis of ALI in recent years, the molecular steps regulating the development of increased lung endothelial and epithelial permeability remain poorly understood, and no specific pharmacological therapies are currently available.During the early phase of ALI, a variety of inflammatory mediators are released into the distal air spaces. 2 Among those, interleukin (IL)-1␤ has been shown to be among the most biologically active cytokines in the lungs early after the onset of ALI. 3-5 Furthermore, IL-1␤ stimulates the production of a variety of chemokines (eg, IL-8, monocyte chemotactic protein [MCP]-1, and macrophage inflammatory protein [MIP]-1␣) 6 involved in epithelial wound repair 7,8 and is a potent inducer of lung fibrosis. 9,10 It has been previously shown in rats that lung vascular permeability increases after short-term exposure of IL-1␣ and IL-1␤ protein when ...

The Broselow tape is an accurate means to assess body weight from length in smaller children; in older children it underestimated body weight. Endotracheal tube size selection by the Broselow tape appears to match the size of the tube used better than the age-based formula. The results in a European sample of children are comparable to the US data.

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