title: Investigation of whether the acute hemolysis associated with Rh(o)(D) immune globulin intravenous (human) administration for treatment of immune thrombocytopenic purpura is consistent with the acute hemolytic transfusion reaction model.
abstract: BACKGROUND
  Immune thrombocytopenic purpura and secondary thrombocytopenia patients treated with Rh(o)(D) immune globulin intravenous (human; anti-D IGIV) have experienced acute hemolysis, which is inconsistent with the typical presentation of extravascular hemolysis -- the presumed mechanism of action of anti-D IGIV. Although the mechanism of anti-D-IGIV-associated acute hemolysis has not been established, the onset, signs/symptoms, and complications appear consistent with the intravascular hemolysis of acute hemolytic transfusion reactions (AHTRs). In transfusion medicine, the red blood cell (RBC) antigen-antibody incompatibility(-ies) that precipitate AHTRs can be detected in vitro with compatibility testing. Under the premise that anti-D-IGIV-associated acute hemolysis results from RBC antigen-antibody-mediated complement activation, this study evaluated whether the incompatibility(-ies) could be detected in vitro with a hemolysin assay, which would support the AHTR model as the hemolytic mechanism.
  
  
  METHODS
  Seven anti-D IGIV lots were tested to determine the RBC antibody identities in those lots, including four lots that had been implicated in acute hemolytic episodes. Hemolysin assays were performed that tested each of 73 RBC specimens against each lot, including the RBCs of one patient who had experienced acute hemolysis after anti-D IGIV administration.
  
  
  RESULTS
  Only two anti-D IGIV lots contained RBC antibodies beyond those expected. No hemolysis endpoint was observed in any of the hemolysin assays.
  
  
  CONCLUSIONS
  Although the findings did not support the AHTR model, the results are reported to contribute knowledge about the mechanism of anti-D-IGIV-associated acute hemolysis and to prompt continued investigation into cause(s), prediction, and prevention of this potentially serious adverse event.
authors.affiliation: Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD 20852, USA. ann.gaines@fda.hhs.gov
authors.forename: Ann Reed
authors.initials: AR
authors.lastname: Gaines
authors.forename: Hallie
authors.initials: H
authors.lastname: Lee-Stroka
authors.forename: Karen
authors.initials: K
authors.lastname: Byrne
authors.forename: Dorothy E
authors.initials: DE
authors.lastname: Scott
authors.forename: Lynne
authors.initials: L
authors.lastname: Uhl
authors.forename: Ellen
authors.initials: E
authors.lastname: Lazarus
authors.forename: David F
authors.initials: DF
authors.lastname: Stroncek
mesh_terms: D000208:Acute Disease; D000744:Anemia, Hemolytic, Autoimmune / Q000209:etiology*; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006461:Hemolysis; D006801:Humans; D008875:Middle Aged; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000628:therapy*; D018029:Rho(D) Immune Globulin / Q000009:adverse effects*
chemical_list: D018029:Rho(D) Immune Globulin