A single-center, retrospective study published in Blood Advances identified risk factors for red blood cell (RBC) alloimmunization in pediatric patients with sickle cell disease (SCD).

“Our results indicate that transfusion during proinflammatory events increases the risk of alloimmunization, and HU [hydroxyurea] therapy does not reduce alloimmunization. Therefore, judicious use of transfusion, especially during proinflammatory events, should be exercised to prevent alloimmunization in patients with SCD,” the study’s authors said.

RBC transfusion during a proinflammatory event increased the likelihood of alloantibody production by 4.22-fold. In particular, parvovirus B19-induced transient aplastic crisis was associated with an increased risk of alloimmunization (odds ratio [OR], 187.76; 95% CI, 4.67-7542; P =.006).

For episodically transfused patients who received transfusion mostly during a proinflammatory event, the likelihood of alloimmunization did not decrease with HU administration (OR, 6.52; 95% CI, 0.85-49.77; P =.071), and was not associated with HU duration (OR, 1.13; 95% CI, 0.997-1.28; P =.056) or HU dose (OR, 1.06; 95% CI, 0.96-1.16; P =.242).

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Conversely, HbS/S and HbS/β0 genotypes (OR, 12.14; 95% CI, 1.64-89.86; P =.015), high transfusion load (OR, 1.02; 95% CI, 1.01-1.04; P =.007), and frequent exposure/chronic transfusion (OR, 17.64; 95% CI, 8.19-38.00; P <.001) were identified as risk factors for alloimmunization in logistic regression analysis.

Moreover, the study found a negative correlation between hemoglobin levels and alloimmunization.

The authors recognized some limitations to the study, including the lack of a follow-up antibody test after the last transfusion of episodically transfused patients and potentially missed antibodies, and the inclusion of all RBC units regardless of RBC phenotypes.

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Furthermore, some participants received transfusions at other centers, leading to missing data in the analysis.

The study included 471 participants (mean age at the end of the study, 12.9±5.2 years) who received a total of 15,960 units of RBCs (median total RBC exposure, 3 units per patient) either episodically (85.0%) or chronically (15.0%). Most (76.2%) episodically transfused patients had also received HU at a median maximum tolerated dose of 29.2 mg/kg/day (median accumulative therapy duration, 4.37 years).

The prevalence of alloimmunization in the study cohort was 11.7% (55/471), and the incidence rate of alloimmunization was 0.36 alloantibodies per 100 transfusions (59 alloantibodies/15,960 RBC units).


Zheng Y, Gossett JM, Chen P-L, et al. Proinflammatory state promotes red blood cell alloimmunization in pediatric patients with sickle cell disease. Blood Adv. Published online April 6, 2023. doi:10.1182/bloodadvances.2022008647