Platelet function abnormalities in KD were first reported by Yamada et al in 1978 (14). Studies in platelet activation markers in KD have subsequently been undertaken in Japan, USA, and Italy [Table.4]. Present study has been undertaken to analyse one of the most sensitive platelet activation markers, i.e. MPAs, by flow cytometry in a North Indian cohort of KD. To the best of our knowledge, MPAs has not been studied in acute and subacute phases of KD till date, and our study is perhaps the first attempt along these lines. Levels of MPA% were significantly elevated in children with KD compared to febrile controls and healthy controls (median levels of 41.3%, 5.98%, and 4.48% respectively, p < 0.001). MPA% levels significantly decreased after treatment with IVIg (median: 41.3% vs 18.5%, p < 0.001) [Fig. 2]. Elevations in MPA% suggest excess activation of platelets in KD compared to other common childhood febrile illnesses. Previous studies report that other platelet activation markers (e.g. neutrophil-platelet aggregates, platelet-derived microparticles, platelet VEGF levels, betathromboglobulin levels, PF4 levels, and platelet CD62P expression) are also elevated in acute phase of KD (7–13).
Median levels of MPA% on follow-up at 3 months were lower compared to levels measured 24 hours after IVIg therapy, but higher than values obtained in age and sex-matched controls. It suggests that patients with KD may have a prolonged endotheliitis even after control of systemic inflammation with IVIg therapy. Laurito et al analyzed MPAs in patients with KD several years after the acute phase (mean interval- 76 months). Authors reported that CD41 expression at baseline and after ADP stimulation was significantly higher in patients compared to controls. However, MPA% levels were not significantly different between two populations (9). In a recent study by Yahata et al., platelet-derived microparticles were found to have rebound elevations in 8 of 14 patients with KD after discontinuation of aspirin (10). In our study also, we found rebound elevation in MPA% levels in 2 patients at 3 months of follow-up. However, majority of patients had lower levels even after discontinuation of aspirin.
Ueno et al. reported that levels of neutrophil-platelet aggregates were significantly higher in patients with CAAs when compared with patients without CAAs (11). In our study, levels of MPA% were not different between patients with CAAs (n = 3) and those without CAAs (n = 11). Apparent discrepancy in results could be explained by differences in ethnicities of the study populations, small sample size in both studies, and differences in methodology of assessment of platelet activation. Ueno et al. also reported that levels of neutrophil-platelet aggregates were significantly lower in patients with KD treated with both IVIg and oral prednisolone than in patients who received IVIg alone (11). Corticosteroids were not used in any patients in our cohort.
A limitation of our study is the small sample size. This is understandable considering the fact that the protocol had to be completed in a limited span of time. Use of an imaging flow cytometry could have accurately captured the aggregates of monocytes and platelets (15), however, we could not use this modality in our study. To conclude, MPA% was significantly elevated in our cohort of children with KD when compared with age and sex-matched febrile and healthy controls. Future long-term studies are warranted to find out whether elevated MPAs in KD would have any clinical implications. This may provide a theoretical basis for additional immunosuppressive and/or antiplatelet therapy in KD.