Hemolytic transfusion reactions after administration of intravenous immune (gamma) globulin: a case series analysis

Abstract

BACKGROUND: This case series summarizes our observations of hemolytic reactions after the administration of large amounts of intravenous immune (gamma) globulin (IVIG). STUDY DESIGN AND METHODS: Cases of hemolysis were identified by a decrease in hemoglobin not otherwise explained following IVIG administration. RESULTS: Sixteen cases were identified over a 21/2-year period at the Ottawa Hospital of approximately 1000 patients receiving IVIG (1.6%). Characteristics of these patients include a large dose of IVIG, female sex, non-O blood group, and underlying inflammatory state. CONCLUSIONS: Significant hemolysis may occur after the administration of large doses of IVIG. A two-step mechanism of hemolysis is proposed, sensitization by ABO isohemagglutinins followed by phagocytosis by activated macrophages. A simple protocol to facilitate the early detection of such cases is presented.

Acute Hemolysis After High-Dose Intravenous Immunoglobulin Therapy in Highly HLA Sensitized Patients

“…However, our sample size limited the ability to detect a significant increase in incidence in the whole population during these years. In their case analysis, Daw et al (11) estimated the incidence of IH in their population to be 1.6% over a 2.5-yr period, which is significantly less than what is reported here (P Յ 0.001). In the NIH IG02 trial, conducted between 1997 and 2000, Ͼ300 infusions of IVIG were given to 48 highly sensitized subjects on hemodialysis.…”

“…However, lyophilized products are also hyperosmolar, which limits their use in patients who are either not on dialysis or have residual renal function because of the risk of osmotic nephropathy or thrombotic events. It has been hypothesized that individuals with an enhanced immunologic state resulting from underlying inflammation may be at increased risk of developing IH (11). All of our cases occurred in patients who were highly sensitized.…”

“…However, there are now many documented cases of IH that occur despite these limits. Anti-A titers Ͼ1:16 are more likely to cause clinically significant hemolysis (11,12). Our evaluation of five different IVIG products showed all of the products to be within the guideline, with the exception of the anti-A titers in the lots of Gammagard liquid and Privigen tested.…”

“…We use a total dose of 2 g/kg given at week 0 and week 4 for desensitization before transplantation (up to a maximum of 140 g for patients Ͼ70 kg). The total dose in our series was either given in 1 or 2 d. IVIG was given over multiple days in other reports (1,(10)(11)(12)15). IH was observed despite dividing the cumulative dose over multiple days.…”

“…There are scattered case reports describing this phenomenon, but it has not yet been described in ESRD patients on dialysis (1,(10)(11)(12)(13)(14)(15). One recent report describes the development of acute kidney injury related to hemoglobinuria as a result of IH (16).…”