The Usefulness of Platelet-derived Microparticle as Biomarker of Antiplatelet Therapy in Kawasaki Disease

Abstract

Little is known about platelet dynamics and the effect of antiplatelet therapy in Kawasaki disease (KD). This study sought to define platelet activation dynamics in KD patients by assaying platelet-derived microparticles (PDMPs). We measured plasma PDMPs levels in 46 patients with KD using an enzyme-linked immunosorbent assay (ELISA). Blood samples were collected before, at 2–5 days, and 9–15 days after intravenous immunoglobulin (IVIG) infusion, 2 months and 4–5 months after the onset of KD. We measured PDMP levels in 23 febrile and 10 afebrile control patients. In the acute phase of KD patients, PDMP levels increased significantly after IVIG treatment (12.04 ± 5.58 nmol before IVIG infusion vs. 19.81 ± 13.21 nmol at 2–5 days after IVIG infusion, P = 0.006). PDMP levels were negatively correlated with age and positively correlated with procalcitonin levels in the acute phase of KD. No significant difference was found in PDMP levels between KD patients with and without coronary artery lesion (CAL). Elevated PDMP levels after IVIG therapy significantly decreased below the pre-IVIG level in subacute phase (19.81 ± 13.21 nmol at 2–5 days after IVIG infusion vs. 8.33 ± 2.02 nmol at 9–15 days after IVIG infusion, P < 0.001), and PDMP levels stayed below the pre-IVIG level in the convalescent phase, during which antiplatelet therapy was given. However, PDMP levels rebounded after discontinuing aspirin in 17 patients. In conclusion, enhanced platelet activation was noted before treatment of KD and peaked immediately after IVIG treatment. Recurrent rising of PDMP levels was observed after discontinuing aspirin, although there were no significant differences between the PDMP levels at 2 months after the onset of KD and those at 4–5 months after the onset of the disease.

Utility of color Doppler echocardiography combined with clinical markers in diagnosis and prediction of prognosis of coronary artery lesions in Kawasaki disease

“…Previous studies have demonstrated that platelet counts and age-corrected hemoglobin can be utilized not only as specific indicators of KD but also as predictors of coronary artery dilatation in patients with complete and incomplete KD, respectively. Elevated platelet counts and CRP levels, and lower hemoglobin and ALB levels are also risk factors for acute coronary artery aneurysms (12,29). In general, these previous studies were in agreement with the univariate analysis in the present study.…”

Is aspirin necessary in the acute phase of Kawasaki disease?

“…All these studies revealed that CAL complications are independent of aspirin dose and argued that high anti‐inflammatory doses may not be necessary in the acute phase of KD. However, a recent study showed that PLTs were activated in the acute phase of KD and that aspirin was useful as anti‐PLT therapy for KD . The present study lacks evidence of aggregation or activation of PLT.…”

Platelet-Derived Extracellular Vesicles as Target of Antiplatelet Agents. What Is the Evidence?

“…Aspirin therapy reduces biomarkers of vascular wall cell activation and large EV shedding from smooth muscle cells and erythrocytes, but not from platelets, although decreases the number of tissue factor–bearing PEVs with similar effects in 43 patients with types 1 and 2 diabetes mellitus (Chiva-Blanch et al, 2016). Referring to a different clinical setting, recurrent increase in circulating large PEVs was observed after discontinuing aspirin in 17 of 46 patients with Kawasaki disease, a chronic inflammatory arterial disease (Kim et al, 2017).…”