Alloimmunization in patients with sickle cell disease and underrecognition of accompanying delayed hemolytic transfusion reactions

Transfusion. 2019 Jul;59(7):2282-2291. doi: 10.1111/trf.15328. Epub 2019 Apr 25.


Background: Patients with sickle cell disease (SCD) often require red blood cell (RBC) transfusions but alloimmunization remains a significant complication. Alloantibodies can lead to delayed hemolytic transfusion reactions (DHTRs) days to weeks after a RBC transfusion, but may be underrecognized in patients with chronic hemolysis.

Study design and methods: This retrospective study aimed to determine the incidence and severity of DHTRs associated with new antibody detection in a cohort of 624 patients with SCD who received transfusion with C-, E-, and K-matched RBCs from primarily African American donors over a 14-year period. We identified potential DHTRs by the change in hemoglobin (Hb) and %HbS at baseline, before transfusion, and up to 30 days after the transfusion that preceded new antibody identification.

Results: Laboratory evidence of a DHTR was associated with 54 of 178 evaluable antibodies at first detection (30%), among which less than half were recognized by the patient or provider at the time of the event. A DHTR was associated with 26% of Rh antibodies identified in patients receiving serologic Rh-matched RBCs, and 38% of non-Rh antibodies. Twenty-one of the 54 DHTRs (39%) were associated with a Hb decline greater than 1 g/dL lower than pretransfusion values. Among these 21 severe DHTRs, Rh specificities were identified in 10 of 12 DHTRs in chronically transfused patients, while non-Rh specificities were associated with seven of nine DHTRs in episodically transfused patients.

Conclusion: High clinical suspicion and monitoring for DHTRs is warranted, as they may be more common in patients with SCD than previously appreciated.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Sickle Cell / blood
  • Anemia, Sickle Cell / immunology*
  • Anemia, Sickle Cell / therapy*
  • Antibody Specificity
  • Black or African American
  • Blood Grouping and Crossmatching / methods
  • Erythrocyte Transfusion / adverse effects
  • Hemoglobins / analysis
  • Humans
  • Isoantibodies / blood
  • Isoantibodies / immunology*
  • Retrospective Studies
  • Rh-Hr Blood-Group System / immunology
  • Time Factors
  • Transfusion Reaction / diagnosis*
  • Transfusion Reaction / epidemiology
  • Transfusion Reaction / immunology*


  • Hemoglobins
  • Isoantibodies
  • Rh-Hr Blood-Group System