ABO zygosity, but not secretor or Fc receptor status, is a significant risk factor for IVIG-associated hemolysis

Eluates from DAT‐positive patients with or without hemolysis after high‐dose IVIG yield predominantly IgG isoagglutinins of IgG2 subclass

“…IgG 2 subclass antibodies also are known to interact with the FcγRIIA receptor on mononuclear phagocytes, and this interaction can be enhanced by specific polymorphisms . Although the patients reported herein were not tested for FcγRIIA polymorphisms, we previously showed in a different cohort of patients with or without hemolysis that there is no correlation of FcγR polymorphisms with IVIG‐associated hemolysis …”

“…In an observational clinical study of IVIG‐associated hemolysis, we previously showed that 32% to 36% of non–blood group O patients who receive IVIG will have some degree of hemolysis . We also investigated whether the hemolysis can be explained by ABO zygosity, secretor status, or FcγR polymorphisms and found that only ABO zygosity is a significant risk factor, with group A 1 B patients at greatest risk . In a parallel study, we examined the IgG subclass of eluted IgG anti‐A and/or anti‐B from patients having a positive direct antiglobulin test (DAT) following IVIG administration of 2 g/kg, with or without hemolysis.…”

“…In a parallel study, we examined the IgG subclass of eluted IgG anti‐A and/or anti‐B from patients having a positive direct antiglobulin test (DAT) following IVIG administration of 2 g/kg, with or without hemolysis. The grading system used for hemolysis ranged from 0 (compensated) to 4 (severe) as previously described . DATs were routinely performed using polyclonal rabbit anti‐IgG and eluates were made using EluKit (Immucor) and stored at –80°C until they could be tested.…”

“…The patient cohort reported herein was a satellite study stemming from our larger prospective study on IVIG‐associated hemolysis and consisted of 22 patients, deliberately selected for subclass determination if they had a positive DAT following IVIG therapy. Of the 22 DAT‐positive patients, 9 did not have evidence of hemolysis following IVIG therapy (DAT range, ± to 2+), while 13 showed evidence of hemolysis (DAT range, ± to 2+) using the Canadian IVIG Hemolysis Pharmacovigilance Group guidelines . We were able to successfully determine the subclass of the IgG isoagglutinin in 10 patients.…”

Fatal acute hemolytic transfusion reaction due to anti‐B from a platelet apheresis unit stored in platelet additive solution

“…Although the described patient had previously undergone a hematopoietic stem cell transplant, the donor was also blood group B. Complement regulator deficiencies have been described in patients with some types of acute leukemias and have also been described in some transfusion recipients to contribute to hemolytic reactions . Further, recipient secretor status and recipient ABO zygosity have been suggested to potentially impact the risk of isohemagglutinin‐mediated hemolysis; donor secretor status may also impact isohemagglutinin titer . The Lewis antigen types of the PLT donor and transfusion recipient in this case are unknown.…”