Severe hemolytic anemia following high-dose intravenous immunoglobulin in myasthenia gravis: an underrecognized, but relevant adverse event

Abstract

Case Presentation: A 37-year-old woman with acetylcholine receptor antibody–positive myasthenia gravis received high-dose intravenous immunoglobulin (2 g/kg over 5 days) due to progressive generalized weakness, mild left ptosis and myasthenic facies. She had no features of respiratory distress and was discharged after clinical stabilization. Within 3 days after treatment completion, she presented with marked fatigue and headache. Laboratory evaluation showed a hemoglobin decrease from 13.5 g/dL (level before immunotherapy) to 6.1 g/dL. Hemolysis markers included reticulocytosis (19%), elevated lactate dehydrogenase (718 U/L), increased red cell distribution width, erythroblasts in peripheral blood, hemoglobinuria without hematuria, and mild hyperbilirubinemia. Direct antiglobulin test was negative. Blood type was AB positive. The temporal association with intravenous immunoglobulin administration, laboratory evidence of hemolysis, and absence of an alternative cause for the condition, supported the diagnosis of immunoglobulin-associated hemolytic anemia. Management included red blood cell transfusion of group O red blood cells, close monitoring, and avoidance of further immunoglobulin exposure. The patient showed progressive and spontaneous hematologic recovery. Discussion: Intravenous immunoglobulin (IVIG) may cause hemolytic anemia, particularly after high-dose therapy. The incidence is uncertain, estimated at approximately 1 per 1000 patients treated. The mechanism involves passive transfer of anti-A and anti-B isoagglutinins, leading predominantly to extravascular hemolysis. It occurs within 10 days after infusion and is defined by a drop in hemoglobin with laboratory evidence of hemolysis after exclusion of other causes. Although a positive direct antiglobulin test is common, its absence does not exclude IVIG-associated hemolysis, as passively transferred antibodies may have already been consumed or cleared from the erythrocyte surface at the time of testing. Risk factors include non–group O blood type, high cumulative dose, and inflammatory or autoimmune conditions. Severe cases requiring transfusion may occur. Final Comments: Severe hemolytic anemia is an uncommon but clinically significant complication of intravenous immunoglobulin therapy. Clinicians should consider this diagnosis in patients presenting with acute anemia after treatment, particularly those with non–group O blood type receiving high-dose therapy, to ensure prompt management and avoid re-exposure.