Establishing Reference Intervals for White Blood Cell and Absolute Neutrophil Counts in Duffy Null Individuals

Background/Objectives: The Duffy (Fy) blood group system, encoded by the ACKR1 gene, plays a key role in transfusion medicine and host susceptibility to malarial infections such as Plasmodium vivax. The Duffy-null phenotype [Fy(a−b−)] is associated with lower baseline white blood cell (WBC) and absolute neutrophil count (ANC) values despite a benign clinical course. This study aimed to establish specific reference intervals for WBC and ANC in Duffy-null individuals to improve diagnostic accuracy and reduce unnecessary clinical interventions. Methods: We conducted a retrospective analysis of 1695 adult patients who underwent complete blood count testing and red blood cell phenotyping between 1 January 2020 and 1 January 2026. Among these, 122 healthy individuals with confirmed Fy(a−b−) phenotype met inclusion criteria. Reference intervals were established using 95% reference interval nonparametric methods in accordance with Clinical Laboratory Standards Institute (CLSI) guidelines. Results: The median WBC and ANC values in the Duffy-null cohort were significantly lower than institutional reference medians (3.24 vs. 6.65 × 103/µL and 1.45 vs. 4.45 × 103/µL, respectively; p < 0.01). The derived 95% reference intervals (WBC: 2.43–7.05 × 103/µL; ANC: 1.01–4.34 × 103/µL) fell below conventional thresholds, with the lower ANC bound below the standard neutropenia cutoff. Conclusions: These findings support the need for Duffy-null-specific hematologic reference ranges. Adoption of such intervals may reduce misclassification, avoid unnecessary diagnostic procedures, and promote personalized clinical care.