Scott Winiecki1, Bethany Baer1, Wambui Chege1, Christopher Jankosky1, Paul Mintz2, Meghan Baker3,4, Tiffany Woodworth3, Michael Nguyen1. 1. Division of Epidemiology, Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, Maryland. 2. Division of Hematology Clinical Review, Office of Blood Research and Review, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, Maryland. 3. Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts. 4. Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Abstract
BACKGROUND: Hemolysis after intravenous immune globulins (IGIVs) is a known complication, but expanding indications and recent manufacturing changes warrant ongoing postmarketing surveillance. Characterization of post-IGIV hemolysis to date has been limited to small case series. STUDY DESIGN AND METHODS: We queried the Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS) from 2007 to 2014. All reported post-IGIV hemolysis cases were classified using a prespecified case definition and a case series analysis performed. We also conducted two assessments using FDA's Mini-Sentinel (MS) system to quantify the risk of hemolysis by six product indications and by IGIV formulation and evaluate the onset interval. RESULTS: A total of 109 FAERS cases met our definition. For cases with available information, 83% (66/80) received IGIV doses of at least 2 g/kg, 98.1% (51/52) had non-O blood group, and 75% (64/85) of events occurred within 4 days of IGIV exposure. We identified 313,045 treatment episodes and 337 post-IGIV hemolytic events in MS from 2006 to 2014, with 72% occurring within 2 days. Rates of hemolysis were highest among patients with Kawasaki disease (KD) and immune thrombocytopenia (ITP). The risk among patients receiving nonlyophilized products was 2.3 times higher than that in patients receiving lyophilized products. CONCLUSION: With the largest case series to date, FAERS data support that higher doses and non-O blood group are key risk factors. The incident rate of post-IGIV hemolysis is estimated at one per 1000 IGIV treatment episodes, with most occurring within 2 days of exposure. The risk is higher in patients with KD and ITP and after receipt of nonlyophilized IGIV.
BACKGROUND:Hemolysis after intravenous immune globulins (IGIVs) is a known complication, but expanding indications and recent manufacturing changes warrant ongoing postmarketing surveillance. Characterization of post-IGIV hemolysis to date has been limited to small case series. STUDY DESIGN AND METHODS: We queried the Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS) from 2007 to 2014. All reported post-IGIV hemolysis cases were classified using a prespecified case definition and a case series analysis performed. We also conducted two assessments using FDA's Mini-Sentinel (MS) system to quantify the risk of hemolysis by six product indications and by IGIV formulation and evaluate the onset interval. RESULTS: A total of 109 FAERS cases met our definition. For cases with available information, 83% (66/80) received IGIV doses of at least 2 g/kg, 98.1% (51/52) had non-O blood group, and 75% (64/85) of events occurred within 4 days of IGIV exposure. We identified 313,045 treatment episodes and 337 post-IGIV hemolytic events in MS from 2006 to 2014, with 72% occurring within 2 days. Rates of hemolysis were highest among patients with Kawasaki disease (KD) and immune thrombocytopenia (ITP). The risk among patients receiving nonlyophilized products was 2.3 times higher than that in patients receiving lyophilized products. CONCLUSION: With the largest case series to date, FAERS data support that higher doses and non-O blood group are key risk factors. The incident rate of post-IGIV hemolysis is estimated at one per 1000 IGIV treatment episodes, with most occurring within 2 days of exposure. The risk is higher in patients with KD and ITP and after receipt of nonlyophilized IGIV.
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