Subjects
Patients with KD were prospectively recruited between April 2015 and May 2019 at our hospital. A diagnosis of KD relied on the standards recommended by the American Heart Association’s Scientific Statement for the diagnosis, treatment, and long-term management of KD7 and was confirmed by two experienced pediatricians (at least one was a KD specialist). Informed written consent was obtained from the parents after the nature of the study had been fully explained to them. The University Ethics Committee on Human Subjects at Sichuan University approved the study.
Exclusion criteria included known patients with congenital or chronic hematologic disease affecting the coagulation cascade; patients with end-stage renal disease requiring dialysis, acute or chronic liver failure, and autoimmune disease; patients who had undergone surgery recently; patients with infectious or inflammatory diseases, and patients who received oral anticoagulant or heparin therapy. A total of 520 patients diagnosed with KD were initially screened for participation in this study. Of these, patients who had received initial IVIG treatment at other medical facilities (n=87), received IVIG treatment within 10 days of fever onset (n=12), or cases where IVIG treatment was initiated before blood sampling (n=17) were excluded. Another 19 patients were excluded because of incomplete laboratory data or lack of follow-up results (Figure 1). Finally, data from 385 patients were analyzed.
All patients received 2 g/kg of IVIG for 24 hours and 30–50 mg/kg/day of aspirin until they were afebrile. Initial IVIG resistance was defined as recurrent or persistent fever or other clinical signs of KD for at least 36 hours but not longer than 7 days after initial IVIG treatment. For patients with initial IVIG resistance, the second IVIG dose (2 g/kg given as a single intravenous infusion) was administered according to expert consensus on the diagnosis and treatment of KD in China. Furthermore, pulse intravenous methylprednisolone (10-30 mg/kg/day for three consecutive days) followed by oral prednisone (2 mg/kg/day) tapered over seven days were additionally administered if the patient had recurrent or persistent fever even after the second IVIG administration. No patients received any additional treatment such as infliximab, plasma exchange, or cytotoxic agents. Coronary artery lesions (CALs) were defined on the normalization of dimensions for BSA as Z scores, according to the AHA scientific statement of KD7.
Patients were subsequently categorized into two groups depending on whether they responded to the initial IVIG treatment (initial IVIG-responsive group, n=326; initial IVIG-resistant group, n=59). The initial IVIG-resistant group was further divided into two subgroups based on the effectiveness of repeated IVIG treatment [repeated IVIG-responsive group (n=36) and repeated IVIG-resistant group (n=23)].