Complementary use of passive surveillance and Mini-Sentinel to better characterize hemolysis after immune globulin

Transfusion. 2015 Jul:55 Suppl 2:S28-35. doi: 10.1111/trf.13116.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Databases, Factual*
  • Female
  • Freeze Drying
  • Hemolysis / drug effects*
  • Humans
  • Immunoglobulins, Intravenous / administration & dosage
  • Immunoglobulins, Intravenous / adverse effects*
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / adverse effects*
  • Male
  • Mucocutaneous Lymph Node Syndrome / drug therapy
  • Mucocutaneous Lymph Node Syndrome / epidemiology
  • Pharmacovigilance*
  • Purpura, Thrombocytopenic, Idiopathic / drug therapy
  • Purpura, Thrombocytopenic, Idiopathic / epidemiology
  • Sentinel Surveillance*
  • United States
  • United States Food and Drug Administration

Substances

  • Immunoglobulins, Intravenous
  • Immunologic Factors