Anticoagulation in Pediatrics: DOACs on the Horizon

Jasmine Manning, PharmD Candidate 2019; Diane Nykamp, PharmD

Disclosures

US Pharmacist. 2019;44(5):HS8-HS12. 

In This Article

Standard Therapy

Warfarin: Warfarin is an oral anticoagulant that acts as a vitamin K antagonist and is used for pediatric patients requiring long-term anticoagulation in the outpatient setting. Indications for long-term anticoagulation include the treatment of univentricular heart, VTE, the use of prosthetic valves in children and adolescents, and aneurysms following Kawasaki disease.[5] The initial dose of warfarin is 0.2 mg/kg orally (maximum 5 mg).[3] However, there are several limitations with the use of warfarin. One major limitation of warfarin is the narrow therapeutic index. A large pediatric retrospective study identified independent risk factors such as Asian race, drug interactions, mitral value replacement, and length of hospital stay that resulted in patients being readmitted to the hospital within 30 days due to warfarin-associated bleeding.[6] Practitioners must also consider that many patients starting warfarin have comorbidities and require multiple medications that cause interactions; there may also be dietary interactions with infant formula that contains a large amount of vitamin K.[2] Drug formulation is a concern as well, as many infants are unable to swallow tablets and warfarin is not commercially available as a liquid. Lastly, frequent visits to a healthcare provider for monitoring of warfarin are difficult and time consuming.

Unfractionated heparin (UFH): UFH is a commonly used IV anticoagulant for primary prophylaxis in the hospital setting, particularly for a patient in the intensive care unit or in preparation for a surgical procedure. Considerations in the pediatric population include the short half-life of UFH and limited data regarding efficacy of protamine to effectively reverse bleeding. The typical loading dose for patients is 75 mg/kg IV over 10 minutes.[3] The maintenance dose is then separated based on age: Infants will receive 28 units/kg/hour; children aged 1 year and older and adolescents will receive 20 units/kg/hour.[3] Limitations on use of UFH are due to the variability and interpretation of the two assays, activated partial thromboplastin time (aPTT) and heparin assay (anti-Xa). Another limitation is the need to extrapolate the adult therapeutic levels to children.[4] A serious adverse reaction related to UFH therapy is heparin-induced thrombocytopenia (HIT). The incidence of HIT is reported to be 2.3% to 3.7%, with 1% to 3% prevalence in children undergoing cardiac surgery.[7]

LMWH: LMWH, administered subcutaneously, has a heparin-like structure, with higher selectivity for factor Xa than for thrombin when compared with heparin. Patients younger than age 2 months typically receive 1.5 mg/kg/dose, and patients older than age 2 months receive 1 mg/kg/dose for VTE treatment.[3] One of the biggest benefits is that the longer half-life and stable pharmacokinetics of LMWH allow for outpatient use. LMWH has no food or drug interactions and requires less monitoring than warfarin. LMWH may require weekly monitoring of anti-Xa levels in children in the inpatient setting requiring therapeutic Xa levels. Although incident rates of HIT with LMWH therapy are unknown, the risk is thought to be lower than with UFH. Protamine is the reversal agent, but it can only partially reverse bleeding.[2] LMWH also requires renal dose adjustments.

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