Description:
<jats:sec><jats:title>BACKGROUND</jats:title><jats:p>Increased reporting of intravenous immunoglobulin (IVIG)‐related hemolytic reactions (HRs) triggered an investigation by the German and Swiss health authorities to identify potential risk factors.</jats:p></jats:sec><jats:sec><jats:title>STUDY DESIGN AND METHODS</jats:title><jats:p>From the EudraVigilance database HRs reported between 2008 and 2013 were retrieved for seven IVIG preparations. HRs were classified as mild to moderate (hemoglobin [Hb] decline < 2 g/dL)] or severe (Hb decline > 2 g/dL) and separately analyzed for IVIG doses of less than 2 g/kg body weight and 2 g/kg body weight or more. It was assessed whether HR reporting rates correlate with the isoagglutinin content of the different preparations.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>Of 569 HR cases retrieved, 103 cases were excluded due to insufficient data, leaving 466 for analysis. Ninety‐three cases were classified as mild to moderate and 373 as severe. Approximately 80% of the severe HRs concerned patients with blood group A and only three patients with blood group O. Testing of isoagglutinin titers revealed substantial differences between the seven preparations. IVIG products with high anti‐A/anti‐B titers (≥32) had elevated HR reporting rates, particularly when cumulative doses at least 2 g/kg were administered.</jats:p></jats:sec><jats:sec><jats:title>CONCLUSION</jats:title><jats:p>The isoagglutinin content of IVIGs correlates with the risk for HRs. Exclusion of high<jats:bold>‐</jats:bold>titer donations and manufacturing steps that deplete isoagglutinins should be considered for risk mitigation. In patients with blood groups A or AB receiving doses of at least 2 g<jats:bold>/</jats:bold>kg, the use of IVIG batches with low isoagglutinin titers should be considered to prevent HRs.</jats:p></jats:sec>