Seminars in thrombosis and hemostasis
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Semin. Thromb. Hemost. · Jul 2008
ReviewThe role of bronchoalveolar hemostasis in the pathogenesis of acute lung injury.
Disturbed alveolar fibrin turnover is intrinsic to acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and pneumonia and is important to its pathogenesis. Recent studies also suggest disturbed alveolar fibrin turnover to be a feature of ventilator-induced lung injury (VILI). ⋯ Several preclinical studies show additional anti-inflammatory effects of these therapies in ALI/ARDS and pneumonia. In this article, we review the involvement of coagulation and fibrinolysis in the pathogenesis of ALI/ARDS pneumonia and VILI and the potential of anticoagulant and profibrinolytic strategies to reverse pulmonary coagulopathy and pulmonary inflammatory responses.
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Critically ill patients often have a low platelet count. A proper identification of the underlying cause of this abnormality is required, because various underlying disorders may necessitate different diagnostic and therapeutic management strategies. ⋯ In case of systemic inflammatory syndromes, such as the response to sepsis, disseminated intravascular platelet activation may occur, which will contribute to microvascular failure and thereby play a role in the development of organ dysfunction. A low platelet count is a strong and independent predictor of an adverse outcome in critically ill patients, thereby facilitating a simple and practical risk assessment in these patients and potentially guiding the use of complex or expensive treatment strategies.
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Surgical patients represent a unique group of patients where therapeutic approaches can be preemptively administered. Pharmacologic strategies to prevent or decrease perioperative bleeding function to attenuate inflammatory responses, reduce hemostatic activation, or provide prohemostatic effects to reduce bleeding and the need for allogeneic transfusions. This article will discuss pharmacologic prohemostatic agents (antifibrinolytics, protamine, desmopressin, fibrinogen, purified protein concentrates, recombinant factor VIIa).
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Semin. Thromb. Hemost. · Jul 2008
ReviewPoint of care coagulation tests in critically ill patients.
Point of care assays for various analytes have been established in critical care, including blood gas analysis, glucose, electrolytes, and markers for cardiac ischemia. Coagulation assays can also be adapted to the critical care environment by using whole blood as sample material and instruments optimized for point of care analysis. ⋯ Point of care coagulation assays help in rapidly establishing a diagnosis, clarifying causes of bleeding, and monitoring therapy. Thrombelastography and similar assays extend the scope of coagulation diagnostics by visualizing the process of clot formation and extending the observation period to provide an estimate of clot stability versus mechanical and proteolytic attack.
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Semin. Thromb. Hemost. · Jul 2008
ReviewThe role of natural anticoagulants in the pathogenesis and management of systemic activation of coagulation and inflammation in critically ill patients.
Critically ill patients often have systemic activation of both inflammatory systems and coagulation. Increasing evidence points to an extensive cross-talk between these two systems, whereby inflammation leads to activation of coagulation and coagulation considerably affects inflammatory activity. The intricate relationship between inflammation and coagulation may have major consequences for the pathogenesis of microvascular failure and subsequent multiple organ failure, as a result of severe infection and the associated systemic inflammatory response. ⋯ Activated coagulation proteases, such as the tissue factor-factor VIIa complex, factor Xa, and thrombin, can bind to protease-activated receptors on various cells, and the ensuing intracellular signaling leads to increased production of proinflammatory cytokines and chemokines. Activated protein C can bind to the protein C receptor on endothelial cells and mononuclear cells, thereby affecting NF-kappaB nuclear translocation and subsequently influencing inflammatory gene expression and inhibition of tissue factor expression on mononuclear cells. Observations in experimental models of targeted disruption of the protein C gene and restoration of the downregulated protein C pathway by administration of recombinant activated protein C support this notion.