Inflammatory markers and extended erythrocyte phenotyping in sickle cell patients: a systematic review of diagnostic and clinical implications

Abstract

Background: Sickle cell disease (SCD) requires chronic blood transfusions, which introduce a severe risk of erythrocyte alloimmunization. This systematic review and meta-analysis evaluate the dual impact of extended red blood cell phenotyping and circulating inflammatory biomarkers on alloimmunization rates.

Methodology: Following PRISMA 2020 guidelines, electronic databases were searched up to April 30, 2026, for multi-continental studies published since 2015. A random-effects model synthesized data from 42 eligible studies to compute pooled prevalence and odds ratios (OR). Meta-regression explored geographic resource inequalities as potential moderators of statistical heterogeneity. Results: The global pooled prevalence of red blood cell alloimmunization across all SCD cohorts was 22.7% (95% CI: 18.4%–27.6%). Stratified analysis revealed that limited ABO/RhD-only matching centers faced a massive 48.3% sensitization rate, whereas centers utilizing extended minor antigen phenotyping (Rh, Kell, Duffy, MNS, Kidd) dropped to 7.1%. Severe inter-study heterogeneity (I² = 87.5%) was fully explained by geographic location (meta-regression p = 0.008), highlighting a critical burden in resource-constrained Central African regions. Furthermore, simultaneous elevation of C-reactive protein, interleukin-6, and serum ferritin significantly heightened the risk of developing alloantibodies, yielding a pooled odds ratio of 3.1 (95% CI: 2.41–3.98, p < 0.001).

Conclusion: Extended immunohematology matching drastically reduces erythrocyte sensitization. Chronic systemic inflammation acts as an independent pro-sensitizing clinical risk factor, lowering the threshold for antibody production. Integrating pre-transfusion inflammatory monitoring and molecular genotyping into routine healthcare pathways is essential to optimize transfusion safety in both high-burden and resource-limited settings.

Keywords: Sickle Cell Disease; Alloimmunization; Extended Erythrocyte Phenotyping; Inflammatory Biomarkers; Systematic Review.

Received Date: April 21, 2026

Accepted Date: May 12, 2026

Published Date: June 01, 2026

Available Online at: https://www.ijsrisjournal.com/index.php/ojsfiles/article/view/784