Endothelial Interactions and Coagulation
Circulating blood is the lifeline of our existence, transporting oxygen, glucose and other substrates for energy production. The circulatory system supplies complements, platelets, and white blood cells to combat infections and repair tissues, as well as platelets and soluble coagulation and anti-coagulation proteins and proteases, to prevent uncontrolled bleeding and clotting. The coordination of these vital functions is orchestrated by a thin layer of cells named the endothelium. Endothelial cells direct blood flow by differentially expressing vasoconstrictors (e.g. endothelin, 20-HETE) and vasodilators (e.g. nitric oxide, prostacyclin). These cells direct white blood cell trafficking by differentially expressing the adhesion molecules endothelium selectin (E-selectin), inter-cellular adhesion molecule (ICAM), and vascular cell adhesion molecule (VCAM). Finally, the endothelium directs clotting by differentially releasing ultra-large von Willebrand factor multimers (initiating platelet aggregation), decreasing thrombomodulin (preventing anticoagulation) and increasing plasminogen-activator inhibitor type-1 (PAI-1) expression preventing fibrinolysis. This chapter focuses on the physiology and pathophysiology of the endothelium and the cellular and soluble coagulation system. The objective of this chapter is to prepare the pediatric intensivist to choose specific and non-specific therapies for critically ill children with thrombotic and/or bleeding disorders.
KeywordsPlasma Exchange Disseminate Intravascular Coagulation Thrombotic Thrombocytopenic Purpura Tissue Factor Pathway Inhibitor Thrombotic Microangiopathy
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