Background: Intravenous immunoglobulin (IVIG) is the mainstay of treatment for Kawasaki Disease (KD). Due to the consolidation of IVIG manufacturers in 2008, different preparations of IVIG are currently available in Canada. An increase in adverse effects, especially hemolytic anemia, has been observed.
Objective: To characterize the natural history of IVIG-associated hemolytic anemia in KD.
Methods: A single-centre retrospective study was conducted at Toronto’s SickKids Hospital between January 2002 and December 2012. Medical records of all KD patients were reviewed and hemolytic anemia identified (drop in hemoglobin ≥20mg/dl post-IVIG treatment with 2 or more of the following criteria: reticulocytosis, positive direct anti-globulin test (DAT), and morphological changes on blood film). For statistical analysis, Chi-square tests and ANOVA with Tukey’s post-hoc correction for multiple comparisons were utilized.
Results: Between 2002 and 2008, 2 of 370 patients diagnosed with KD who received Iveegam had hemolytic anemia (0.5%). After 2008, the rates of IVIG-associated hemolysis were as follows: Privigen 17% (8/48, p<0.001), Gammagard 3.3% (4/121) and Gamunex 2.3% (3/130). Retreatment rates were significantly higher in the hemolysis group (64% vs. 22%, p<0.001), and there was a trend showing more patients with larger aneurysms (Z-score >5) in the hemolysis group (17% vs. 5.3%). All patients who hemolyzed had non-O+ blood types. Out of the 17 patients with hemolysis, 9 required red cell transfusions (60%). Starting in 2012, a detailed hemolysis work-up was included as standard protocol for all KD patients. Hemolysis was mediated by anti-blood group A & B antibodies resulting in DAT positivity, but no complement fixation. This extravascular hemolysis was maximal at 72 hours post-IVIG infusion and appeared to be dose dependent.
Conclusions: Hemolysis is seen in up to 17% of those receiving new IVIG preparations, which also appear to be less efficacious - associated with treatment failure and, possibly, poor coronary outcome. There are important implications for patient safety. Further study is required to develop evidence-based guidelines to improve our management of these children.