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Under normal homeostatic conditions, the human body is at a constant balance between clot formation and destruction. Physiologic hemostasis occurs as a result of a complex interaction among platelets, the vascular endothelium, the coagulation cascade, and the fibrinolytic system. Any disorder or xenobiotic that alters this equilibrium can produce either excessive thrombosis or hemorrhage. Numerous pharmacologic agents have been developed to prevent thrombus formation by interfering with platelet adhesion or aggregation, or by interfering with the clotting cascade. Numerous additional drugs, including those working by novel mechanisms, are in various stages of development.1

Thrombus formation involves an interaction between the coagulation cascade and platelets. The coagulation cascade (Figure 178-1) involves interplay between the contact activation pathway (formerly called the intrinsic system) and the tissue factor pathway (formerly referred to as the extrinsic system). This interaction ultimately produces thrombin, a critical enzyme in the coagulation system.2,3 The binding of tissue factor to factor VII activates the latter (factor VIIa), which subsequently catalyzes the conversion of factors IX and X to their active forms. The common pathway begins with the conversion of factor X to its active form (Xa), which in turn converts prothrombin to thrombin, which ultimately catalyzes the conversion of fibrinogen to fibrin.

Simultaneously, clot formation is also occurring at the local level, at the site of the damaged endothelium. The damaged endothelium releases endothelin, which results in vasoconstriction, one of the first steps in achieving hemostasis. The damaged endothelium also expresses tissue factor, ensuing platelet binding to the endothelium.4,5 Platelets are secured to the vascular injury via glycoprotein Ib/V/IX. Von Willebrand factor (VWF) is critical for the integrity of this glycoprotein complex.6 Platelet adhesion involves platelets binding to the damaged endothelium VWF.6,7 Platelet activation occurs in response to numerous mediators, including adenosine diphosphate (ADP), thromboxane A2, epinephrine, and thrombin.6 Ultimately, platelet aggregation occurs via the glycoprotein IIb/IIIa receptor.8 The absolute stability of the aggregated platelets requires fibrin connect the glycoprotein IIb/IIIa complexes between platelets.6

Because thrombus development is complex with numerous steps required for successful formation, multiple different classes of drugs, each with unique mechanisms of action have been developed to halt this process. This chapter focuses on different drugs the pediatric patient may be administered therapeutically or accidentally. The pathophysiology of each drug along with laboratory monitoring and treatment strategies are discussed. As specific recommendations for the management of pediatric patients are often lacking, recommendations are extrapolated from the adult literature, where applicable, and adjusted for pediatric patients when appropriate.



Vitamin K antagonists are used medically (e.g. warfarin) as well as industrially (e.g. long-acting anticoagulant rodenticides [LAAR], or “superwarfarins”) (Figure ...

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