What is the appropriate aspirin dosing regimen (high‑dose then low‑dose) for a child with Kawasaki disease to prevent cardiac complications, including weight‑based doses and age considerations?

Aspirin Dosing in Kawasaki Disease to Prevent Cardiac Complications

Start with high-dose aspirin 80–100 mg/kg/day divided into four doses during the acute phase, continue until the child has been afebrile for 48–72 hours, then switch to low-dose aspirin 3–5 mg/kg/day once daily and maintain for 6–8 weeks if no coronary abnormalities develop—or indefinitely if coronary artery abnormalities are present. 1, 2

Acute Phase: High-Dose Aspirin

• Administer 80–100 mg/kg/day divided into four doses starting at diagnosis, given concurrently with IVIG 2 g/kg as a single infusion. 1, 2

• The high-dose regimen provides anti-inflammatory effects and appears to have an additive benefit when combined with IVIG, though aspirin alone does not reduce coronary artery abnormality rates. 1, 2

• Continue high-dose aspirin until the patient has been afebrile for 48–72 hours. 1, 2, 3

• Some institutions continue high-dose aspirin until day 14 of illness and 48–72 hours after fever cessation, though practice varies. 1

Transition to Low-Dose Aspirin

• Once fever resolves for 48–72 hours, switch to low-dose aspirin 3–5 mg/kg/day given once daily for antiplatelet effects. 1, 2, 3

• Maintain low-dose aspirin until 6–8 weeks after disease onset if serial echocardiograms show no coronary abnormalities. 1, 2, 3

• For children who develop any coronary artery abnormalities, continue low-dose aspirin indefinitely. 1, 2, 3

Long-Term Antiplatelet Strategy Based on Coronary Findings

• No coronary abnormalities: Discontinue aspirin at 6–8 weeks after disease onset. 2

• Small coronary aneurysms: Continue low-dose aspirin 3–5 mg/kg/day indefinitely. 2, 3

• Moderate aneurysms (4–6 mm): Low-dose aspirin 3–5 mg/kg/day plus clopidogrel 1 mg/kg/day (maximum 75 mg/day). 2

• Giant aneurysms (≥8 mm): Low-dose aspirin 3–5 mg/kg/day plus warfarin (target INR 2.0–3.0) or therapeutic low-molecular-weight heparin. 2

Critical Safety Considerations

• Never co-administer ibuprofen with aspirin in children taking aspirin for antiplatelet effects, as ibuprofen antagonizes the irreversible platelet inhibition induced by aspirin. 1, 2, 3

• Administer annual influenza vaccination to all children on long-term aspirin therapy to reduce the risk of Reye syndrome during influenza infection. 1, 2, 3

• Discontinue aspirin immediately if the child develops influenza or varicella infection and substitute an alternative antiplatelet agent (such as clopidogrel) during the illness to maintain antithrombotic coverage while avoiding Reye syndrome risk. 1, 3

• Regarding varicella vaccination: Although vaccine manufacturers recommend avoiding salicylates for 6 weeks after varicella vaccine, physicians must weigh the theoretical vaccine-related risk against the known risk of wild-type varicella in children on long-term salicylate therapy. Some clinicians substitute another antiplatelet medication during the 6-week post-vaccination period. 1, 2

Evidence Regarding Aspirin Dose Controversy

• Recent research suggests that lower doses of aspirin (20–29 mg/kg/day or even 3–5 mg/kg/day from the start) do not increase the risk of coronary artery damage compared to traditional high doses of 30–50 mg/kg/day or 80–100 mg/kg/day. 4, 5, 6

• One retrospective study of 851 patients found that high-dose aspirin in the acute phase was associated with lower hemoglobin levels, higher CRP, and delayed decrease in inflammatory markers, with no benefit in IVIG resistance rates, coronary artery lesion formation, or duration of hospitalization. 5

• Another study of 2,369 patients showed no difference in coronary artery aneurysm rates at 2 weeks or 3–4 weeks between aspirin doses of 20–29 mg/kg/day versus 30–50 mg/kg/day. 4

• However, the American Heart Association guideline remains the standard of care and continues to recommend high-dose aspirin 80–100 mg/kg/day in the acute phase, based on decades of clinical experience and the established safety profile when combined with IVIG. 1, 2

Common Pitfalls to Avoid

• Do not rely on aspirin alone to prevent coronary complications—IVIG 2 g/kg is the cornerstone of treatment and must be given within the first 10 days of fever onset. 2

• Do not stop low-dose aspirin prematurely in children with any persistent coronary abnormalities; these patients require indefinite antiplatelet therapy. 2, 3

• Do not use ESR to monitor inflammation after IVIG—use CRP instead, because IVIG artificially elevates ESR values. 2

• Infants under 1 year are at highest risk for incomplete presentations and have the highest rates of coronary aneurysms if untreated, so maintain a high index of suspicion and treat promptly. 2