Case Presentation: A 21-month-old previously healthy female presented with nine days of fever. Parents endorsed hand and feet swelling, and a red rash that resolved prior to presentation. She was fussy and had cracked lips. Labs were notable for C-reactive protein (CRP) of 18.52 mg/dL, erythrocyte sedimentation rate (ESR) >130 mm/hr, WBC 17.3 x 109/L, and hemoglobin of 9.3 g/dL. SARS-CoV2 nasopharyngeal swab and SARS-CoV2 IgG antibodies were negative. Atypical Kawasaki Disease (KD) was diagnosed and a transthoracic echocardiogram (TTE) showed no coronary artery aneurysms (CAA). The patient was determined to be at low risk for CAA formation based on the Son et. al risk model1, and therefore was treated with one dose of IVIG (2 g/kg) and aspirin (30-50 mg/kg/day). She continued to be febrile with increasing thrombocytosis and CRP concerning for IVIG-resistance. She was given a second dose of IVIG and started on IV methylprednisolone. About 48 hours after her second dose of IVIG, she had tachycardia and conjunctival pallor. Hemoglobin was 6.2 g/dL, with elevated LDH, reticulocyte percentage, normal bilirubin and haptoglobin. Anti-A antibodies were identified in the eluate concerning for hemolytic reaction. She received one unit of blood with improvement in her hemoglobin. The patient’s inflammatory markers down trended and repeat TTE had no evidence of CAA at discharge.
Discussion: The treatment of KD aims to reduce inflammation and prevent CAA development. Guidelines recommend a single dose of IVIG and aspirin followed by observation for at least 36 hours for recurrence of fever. Recurrence of fever after 36 hours post-infusion indicates IVIG resistance and a repeat dose is recommended. While IVIG is effective in ~90 % of patients, the treatment is not benign. Hemolytic anemia, caused by the presence of anti-A and/or anti-B antibodies in IVIG products, is an under recognized complication of IVIG therapy. The incidence of hemolysis due to IVIG is ~1/1000 and typically occurs within 48 hours of exposure5. A case series identified four patients with hemolysis after receiving IVIG for management of KD7. All patients had a positive direct Coomb’s with most having antibodies in the eluates prepared from their red cells7. Three of four patients had indirect bilirubin in the normal range and only two had low haptoglobin.
Conclusions: Pediatric hospitalists frequently treat patients with KD. This case illustrates an uncommon yet clinically significant response to treatment with IVIG. Patients with non-O blood groups who receive high doses (>2g/kg) of IVIG are at highest risk for having a hemolytic reaction4. Hospitalists should be aware of this potential complication and monitor for signs of hemolysis including tachycardia, fatigue, dark urine, and pallor after infusion. Further, assessing patients’ risk factors for hemolytic reaction will help identify patients who require monitoring of hemoglobin after IVIG infusion.