Roger Berg1, Amgad Shebl2, Mary Clare Kimber3, Maria Abraham4, George B Schreiber3. 1. Baxter Innovations GmbH, Vienna, Austria. 2. CSL Behring, Marburg, Germany. 3. Plasma Protein Therapeutics Association, Annapolis, Maryland. 4. Statistics Collaborative, Inc., Washington, DC.
Abstract
BACKGROUND: Objectives of this study were to identify possible patient and product risk factors for intravenous immune globulin (IVIG)-associated hemolysis, a recognized side effect of IG therapy; analyze IVIG indications; and examine dose levels (g/kg body weight) and total IVIG dose administered. STUDY DESIGN AND METHODS: Reports of IVIG-associated hemolysis for 10 years (2003-2012) for four participating IG manufacturers were identified using a uniform case definition (Standardized MedDRA Query "Hemolytic disorders," Broad Scope, Version 16.0) and analyzed. RESULTS: IVIG-associated hemolysis appears to occur predominantly at dose levels exceeding 0.5 g/kg, with 72% of cases with known dose information having dose levels between 1 and 2.5, and can affect patients at any age, without a clear gender preference. No association was found between hemagglutinin exposure and development of hemolysis, nor between dose levels and odds of receiving a transfusion to treat hemolysis. Patients with blood group AB may be at higher risk of hemolysis than those with group A or B. CONCLUSION: Data examined confirm that IVIG-associated hemolysis predominantly occurs following infusion of high IVIG doses, and can affect patients at every age of both genders. While presence of hemagglutinins appears to play a major role in pathogenesis of hemolytic disorders, high hemagglutinin titers of IVIG products themselves seem to be of less relevance, indicating that the pathomechanism of IVIG-associated hemolysis may be related to the presence, but not the absolute amount, of hemagglutinins. Patients with hemolysis had additional hemolytic risks such as multiple comorbidities and medication use. IG-treated patients with multiple risks should be closely monitored for hemolysis.
BACKGROUND: Objectives of this study were to identify possible patient and product risk factors for intravenous immune globulin (IVIG)-associated hemolysis, a recognized side effect of IG therapy; analyze IVIG indications; and examine dose levels (g/kg body weight) and total IVIG dose administered. STUDY DESIGN AND METHODS: Reports of IVIG-associated hemolysis for 10 years (2003-2012) for four participating IG manufacturers were identified using a uniform case definition (Standardized MedDRA Query "Hemolytic disorders," Broad Scope, Version 16.0) and analyzed. RESULTS: IVIG-associated hemolysis appears to occur predominantly at dose levels exceeding 0.5 g/kg, with 72% of cases with known dose information having dose levels between 1 and 2.5, and can affect patients at any age, without a clear gender preference. No association was found between hemagglutinin exposure and development of hemolysis, nor between dose levels and odds of receiving a transfusion to treat hemolysis. Patients with blood group AB may be at higher risk of hemolysis than those with group A or B. CONCLUSION: Data examined confirm that IVIG-associated hemolysis predominantly occurs following infusion of high IVIG doses, and can affect patients at every age of both genders. While presence of hemagglutinins appears to play a major role in pathogenesis of hemolytic disorders, high hemagglutinin titers of IVIG products themselves seem to be of less relevance, indicating that the pathomechanism of IVIG-associated hemolysis may be related to the presence, but not the absolute amount, of hemagglutinins. Patients with hemolysis had additional hemolytic risks such as multiple comorbidities and medication use. IG-treated patients with multiple risks should be closely monitored for hemolysis.
Authors: Christine W Bruggeman; Sietse Q Nagelkerke; Wendy Lau; Cedric Manlhiot; Masja de Haas; Robin van Bruggen; Brian W McCrindle; Rae S M Yeung; Taco W Kuijpers Journal: Blood Adv Date: 2020-07-28