Establishing Absolute Neutrophil Count and White Blood Cell Count Reference Intervals for the Duffy Null Population

Most reference intervals (RI) for absolute neutrophil count (ANC) and white blood cell count (WBC) in the United States (US) are not representative of people with the Duffy null phenotype (10% of the US population), which leads to misdiagnoses and inequity in care. We aimed to verify the adult Duffy null ANC RI and develop WBC and ANC RIs for pediatrics. 1,412 healthy Duffy null participants from 23 sites were included. All sites agreed on eligibility criteria. Otherwise, this was a pragmatic design with site-specific variation in collection approach. ANC and WBC were stratified into 5 age categories: 6 months-2 years, 3-6 years, 7-12 years, 13-17 years, and 18+ years. RI were calculated by Clinical and Laboratory Standards Institute guidelines. Duffy null-specific ANC RI were 0.53-4.50×109/L (6 months-2 years, n=184), 0.78-4.67×109/L (3-6 years, n=160), 0.87-5.34×109/L (7-12 years, n=190), 0.90-4.89×109/L (13-17 years, n=216), and 1.03-7.30×109/L (18+ years, n=662). 25% of adults had ANC <2.00×109/L and 24-53% of children had ANC <1.50×109/L. Sensitivity analyses did not show any significant differences in ANC RI when accounting for blood draw type, setting, collection site, hematology analyzer, or hemoglobin and platelet counts. This study provides the first report of Duffy null-specific pediatric ANC and WBC RI, as well as a large-scale verification of adult Duffy null-specific ANC and WBC RI. Adoption of Duffy null-specific RIs is necessary for the accurate interpretation of laboratory values that will support appropriate and equitable medical decision-making.