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

Abstract

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.

Conflict of interest statement

CONFLICT OF INTEREST

The authors have disclosed no conflicts of interest.

© 2019 AABB.

Figures

Fig. 1.

Antibody specificities identified in patients with SCD transfused with prophylactic ABO, D, C, E, and K serologic matched RBCs. (A) A total of 175 antibodies occurred during chronic transfusion therapy (■) and 64 antibodies formed after an episodic transfusion (□). (B) Antibodies detected to common Rh specificities in patients whose RH genotype predicts RBC expression of partial , altered (■), or conventional antigen or absence of the antigen (□). RHD*DAU0 and RHCE*ce48C, which encode proteins that have not been shown to lack epitopes are described as altered but not partial antigens.

Fig. 2.

RBC unit exposure at time of first detection of new antibody. The RBC unit exposure for each antibody at first detection is shown as a circle, along with the median and interquartile range. *Seven specificities were identified with more than 800 unit exposures (882 units for anti-D, 1359 for anti-C, 864 for anti-e, 1496 for anti-Fya, 896 for anti-Lea, 813 for anti-V/VS, 1492 for anti-Kpa).

Fig. 3.

Laboratory evidence of DHTRs. (A) Laboratory evidence of a DHTR in a patient chronically receiving RBCs. Arrow denotes time at which a DHTR was suspected. Dotted line indicates the patient’s mean pretransfusion Hb level and %HbS for the 12 months preceding the DHTR. (B) Number of antibodies at first detection that were or were not (□) associated with a DHTR according to specificity.