Kawasaki disease and aspirin

The use of high-dose aspirin therapy for Kawasaki disease,
recommended by Dr Goel and his colleagues (June 25, p 144),
requires comment. In the acute phase of the disease, high-dose
aspirin is appropriate in an effort to ameliorate the acute
inflammatory response and reduce fever. The dose recommended,
30 mg/kg/day, may be suitable, although this dose was no-better than
a cephalosporin antibiotic in preventing the development of
coronary-artery aneurysms. In the convalescent phase of the
illness, when the incidence of sudden death is approximately 2%,
the primary aim is to prevent death. Low-dose aspirin is likely to
have a role in preventing coronary-artery occlusion during this
phase.
It is suggested that the reason why the dosage of aspirin is so
critical in haemostasis is that it inhibits cyclo-oxygenase, which is
present in both platelets and vessel walls. In the platelets the
products of cyclo-oxygenase action include thromboxane A2 and
malondialdehyde, both of which aggregate platelets. In the vessel
wall the same enzyme produces prostacyclin, which inhibits platelet
aggregation. Thromboxane A2 is also a vasoconstrictor and
prostacyclin a vasodilator. Several studies have shown that different
doses of aspirin may swing the haemostatic mechanism in one
direction or the other by altering the balance of platelet aggregating
and aggregation-inhibiting influences. O’Grady and Moncada
showed that 0 - 3 g aspirin prolonged the bleeding time in 6 adult
3 Hamashima Y, Kishi K, Tasaka K. Rickettsia like bodies in infantile mucocutaneous
lymph node syndrome. Lancet 1973; ii: 42.
1. Kato U, Koite S, Yokohama T. Kawasaki disease: effect of treatment on coronary artery
involvement. Pediatrics 1979; 63: 175-79.
volunteers, whereas 3-9 g g had no effect.2 Masotti et al3 gave
different single doses of aspirin to 25 volunteers and measured
malondialdehyde, platelet aggregation, and prostacyclin levels after
forearm ischaemia at different times. They found that the inhibition
of platelet aggregation was proportional to dose at 2-5 mg/kg and
was barely increased by larger doses, and that prostacyclin
production was inhibited by larger doses (8 and 10 mg/kg). Larger
doses of aspirin therefore favour platelet aggregation. The duration
of inhibition was less than 24 h for prostacyclin and longer than 72 h
for platelet aggregation. The reason for the differential effect is
probably that aspirin acetylates cyclo-oxygenase irreversibly in
platelets but reversibly in blood-vessel walls.4
Clearly it would be unwise to rely on studies in healthy adults for
treatment recommendations in ill children with high platelet counts. The present recommendation of 30 mg/kg/day for three
months is based on work presented at conference proceedings only. 5
Further work needs to be done to examine the issue. Until then
3’ 5-5 - 0 mg/kg of aspirin every second or third day would seem the
most appropriate therapy for these children in the convalescent
phase of the illness