Antithrombotic Therapy in Children: Therapeutic Range
Therapeutic Range: The most commonly used test for monitoring oral anticoagulant therapy is the prothrombin time (PT), reported as an INR. Unfortunately, most pediatric studies have not reported their PT results as INRs, which hinders the interpretation and generalizabil-ity of the results. Currently, therapeutic INR ranges for children are extrapolated directly from recommendations for adult patients because there are no clinical trials that have assessed the optimal INR range for children based upon clinical outcomes. The recommended therapeutic range for the treatment of venous thrombotic disease is an INR between 2.0 and 3.0. The recommended therapeutic range for children with mechanical prosthetic heart valves is an INR between 2.5 and 3.5. Experience with INR ranges of 1.5 to 2.0 is minimal in pediatrics. However, the available biological data (see previous section) and limited clinical data suggests that optimal therapeutic INR ranges may be lower in children. Clinical trials are urgently needed to test this hypothesis.
Dose Response: Of the five publications that provide information on loading doses for oral anticoagulant therapy in children, four were level V and one was level IV. Of the seven publications that provide information on maintenance doses for oral anticoagulants required to achieve an INR between 2.0 and 3.0 in children, five are level V and two are level III. Maintenance doses for oral anticoagulants are age dependent, with infants having the highest and teenagers having the lowest requirements. The published age-specific, weight-adjusted doses for children vary due to the different study designs, patient populations, and possibly, the small number of children studied. Allergy relief itat on The largest cohort study (n = 115) found that infants required an average of 0.32 mg/kg and teenagers 0.09 mg/kg of warfarin to maintain a target INR of 2 to 3. For adults, weight-adjusted doses for oral anticoagulants are not precisely known but are in the range of 0.04 to 0.08 mg/kg for an INR of 2 to 3 The mechanisms responsible for the age dependency of oral anticoagulant doses are not completely clear. Table 6 provides a nomogram for loading and monitoring oral anticoagulants in children. Guidelines for the duration of therapy with oral anticoagulants in children reflect recommendations for adults with similar disorders. Patients with their first venous thrombotic event are treated for 3 months, while those with mechanical prosthetic heart valves are treated for life. Optimal treatment for children with recurrent DVT/PE, beyond the initial treatment, is uncertain.