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The hemostatic mechanism is a dynamic system that maintains the fluidity of blood, while allowing for the formation of blood clots to prevent bleeding subsequent to blood vessel injury. These interrelated components consist of vessel walls (including endothelial cells), platelets, coagulation factors, inhibitors, and the fibrinolytic mechanism. Perturbation of any of these systems can lead to disease states that are thrombotic or hemorrhagic in nature. This chapter discusses the normal and abnormal hemostatic system in children, with emphasis on disorders involving the endothelium, platelets, and defects in coagulation and fibrinolysis.

Role of the Endothelium

The endothelium is comprised of a single layer of endothelial cells lining the inner lumen of the vascular wall and the underlying basement membrane matrix that provides structural and functional support to the entire vascular network. The primary role of the endothelial cells is to act as a selective barrier between the circulating blood and the underlying tissues, ensuring vascular patency by providing a nonthrombogenic surface for circulating blood under normal, physiologic conditions. In addition, the endothelium interacts with the underlying matrix by directing the passage of molecules, nutrients, solutes, and hormones from the blood. Blood flow within the vasculature can be altered by the endothelial cells that work in conjunction with pericytes (specialized smooth muscle cells) and basement membrane (BM) matrix.1,2 This is accomplished by modulating vascular tone through contraction3-5 or relaxation6-8 of the smooth muscle cells by releasing vasoactive substances into the adjacent milieu, ultimately influencing blood flow and pressure and permeability. Intact endothelial cells inhibit platelet adhesion by production of nitric oxide (NO) and prostaglandin I2 (PGI2), which also has a vasodilatory effect. Weibel-Palade bodies in endothelial cells are important for storage and sequestration of the largest multimers of von Willebrand factor (vWF).9,10 Endothelial cells also produce tissue factors and tissue factor pathway inhibitor (TFPI), tissue plasminogen activator (t-PA), prostacyclin, antithrombin (AT), and thrombomodulin, as well as the surface protein for activation of protein C (PC).

The multifunctionality of the endothelium also includes metabolic processes that release substances into the bloodstream, influencing conditions both locally and systemically in the blood, and basal lamina, to sustain and direct BM matrix composition and function. BMs have unique composition dependent on the specific environment of the vasculature (tissue specific).11-13 In constant contact with cells, BM plays a vital role by providing structural support, compartmentalization of tissues, and regulation of cell behavior, such as cell attachment, migration, differentiation, and growth.11,14-17 The thrombogenic subendothelial layer is composed of collagen, elastin, and fibronectin. The main component of the BM is collagen (mainly, type IV), comprising ~50% of its protein.12,13,18 Endothelial cells are capable of altering the surrounding basement membrane matrix by secreting collagenases.19-21 Preserving the integrity of the endothelium in an ever-changing environment is essential because disruption to any of these systems that alter the ...

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