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)].