Antithrombotic Therapy in Children: Adverse Effects of Antiplatelet Agents
Therapeutic Range, Dose Response, and Monitoring of Antiplatelet Agents: There is no therapeutic range for or need to monitor aspirin, the most commonly used antiplatelet agent, and no studies that compare different doses of aspirin in children. Empiric low doses of 1 to 5 mg/kg/d have been proposed as adjuvant therapy for Blalock-Taussig shunts, some endovascular stents, and some cerebrovascular events. For mechanical prosthetic heart valves, aspirin doses of 6 to 20 mg/kg/d were used in nine studies, either alone or in combination with 6 mg/kg/d of dipyridamole in 3 divided doses. High dose aspirin, 80 to 100 mg/kg/d, is used in Kawasaki’s disease during the acute phase (up to 14 days), then 3 to 5 mg/kg/d for 7 weeks or longer if there is echocardiographic evidence of coronary artery abnormalities. The effects of aspirin last for approximately 7 days. The second most commonly used antiplatelet agent, prescribed for patients with mechanical prosthetic heart valves, is dipyridamole in doses of 2 to 5 mg/kg/d. Glycoprotein (GP)IIb-IIIa antagonists are a new class of antiplatelet drugs that are now available in IV form (ReoPro, Aggrastat, Intregilin) and will soon be available in oral form. These drugs, which are either chimeric antibodies (ReoPro; Centocor; Malvern, PA), peptides (Integrelin; COR Therapeutics; South San Francisco, CA), or nonpeptide small molecules (Aggrastat; Merck; West Point, PA), act by binding to the platelet surface GPIIb-Illa complex, thereby inhibiting fibrinogen-mediated platelet aggregation. Because fibrinogen binding to the platelet GPIIb-IIIa complex is the final common pathway of platelet aggregation, these drugs are powerful antiplatelet agents. However, there are as yet no reports of their use in children. Although GPIIb-IIIa antagonist therapy may need to be monitored, the optimal assays are still under investigation. The appropriate therapeutic ranges for these assays may prove to be different in children because of the agent-dependent differences in platelet function described above. buying antibiotics online
Adverse Effects of Antiplatelet Agents: Newborns may be exposed to antiplatelet agents due to maternal ingestion (aspirin as treatment for preeclampsia) or therapeutically, (indomethacin as medical therapy for patent ductus arteriosus). Clearance of both salicylate and indomethacin is slower in newborns, potentially placing them at risk for longer periods of time. However, in vitro studies have not demonstrated an additive effect of aspirin on the hypo-function of newborn platelets, and evidence linking maternal aspirin ingestion to clinically important bleeding in newborns is weak (level V). Indomethacin does prolong the bleeding time in newborns, but the evidence linking indomethacin to intracranial hemorrhage (ICH) is weak.