Abstract
We examined risk factors for RBC alloimmunization in pediatric patients with sickle cell disease (SCD), focusing on recipients' inflammatory state at the time of transfusion and anti-inflammatory role of hydroxyurea (HU). Among 471 participants, 55 (11.70%) participants were alloimmunized and formed 59 alloantibodies and 17 autoantibodies with an alloimmunization rate of 0.36 alloantibodies per 100 units. Analysis of 27 participants who formed alloantibodies with specificities showed 23.8% (30/126) of units transfused during a proinflammatory event resulted in alloantibody formation compared to 2.8% (27/952) of units transfused at steady state. Therefore, transfusion during proinflammatory events increased the risk for alloimmunization (odds ratio [OR]: 4.22; 95% confidence interval [CI]: 1.64-10.85; p = 0.003). Further analysis of all the 471 participants showed alloimmunization of episodically transfused patients who received transfusion mostly during proinflammatory events was not reduced by HU therapy (OR: 6.52; 95% CI: 0.85-49.77; p = 0.071), HU therapy duration (OR: 1.13; 95% CI: 0.997-1.28; p = 0.056) or HU dose (OR: 1.06; 95% CI: 0.96-1.16; p = 0.242). The analysis also identified high transfusion burden (OR: 1.02; 95% CI: 1.003-1.04; p = 0.020) and HbSS and HbSβ0-thalassemia genotypes (OR: 11.22, 95% CI: 1.51-83.38, p = 0.018) as additional risk factors for alloimmunization. In conclusion, the inflammatory state of transfusion recipients affects the risk of RBC alloimmunization, which is not modified by HU therapy. Judicious use of transfusion during proinflammatory events is critical for preventing alloimmunization.
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