Antithrombotic Therapy in Children: Antithrombotic Agents and the Young
Antithrombotic Agents and the Young
Heparin Therapy in Pediatric Patients
Mechanism of Action: Heparin’s anticoagulant activities, which are mediated by catalysis of antithrombin (AT), can be impaired in the presence of decreased plasma levels of AT. Some pediatric patients requiring heparin therapy have very low levels of AT reflecting physiologic, congenital, and/or acquired etiologies. For example, plasma concentrations of AT are physiologically low at birth (approximately 0.50 U/mL) and increase to adult values by 3 months of age. Sick premature newborns, a population of children at significant risk for thrombotic events, frequently have plasma levels of AT that are <0.30 U/mL, potentially influencing their response to heparin.5 Fetal reference ranges are now available and show that AT levels range from 0.20 U/mL to 0.37 U/mL at gestational ages of 19 to 38 weeks.
Heparin functions as an antithrombotic agent by catalyzing AT’s ability to inactivate specific coagulation enzymes, of which thrombin is the most sensitive. The capacity of plasmas from newborns to generate thrombin is both delayed and decreased compared to adults; it is similar to plasma from adults receiving therapeutic amounts of heparin. Following infancy, the capacity of plasmas to generate thrombin increases, but throughout childhood, remains approximately 25% less than that of adults website my canadian pharmacy online. At heparin concentrations in the therapeutic range, the capacity of plasma to generate thrombin is delayed and decreased by 50 to 25% in newborns and children, respectively, compared to adults. These observations support the hypothesis that optimal dosing of heparin will differ in pediatric patients and adults.
Therapeutic Range: Therapeutic doses of heparin are the amounts of heparin required to achieve the adult therapeutic range based upon the activated partial thromboplastin time (APTT). The recommendations for standardizing APTT values to heparin levels in adults should be extrapolated to children (Table 1). The recommended therapeutic range for the treatment of venous thrombotic disease in adults is an APTT that reflects a heparin level by protamine titration of 0.2 to 0.4 U/mL or an anti-factor Xa level of 0.3 to 0.7 U/mL. In pediatric patients, APTT values correctly predict therapeutic heparin concentrations approximately 70% of the time.