Abstract
ABSTRACT: Laboratory reference intervals must reflect population diversity for accurate medical decisions. The Duffy-null variant lowers absolute neutrophil counts (ANC), but existing dedicated reference intervals are based on a single African American cohort. The impact across other ethnic groups and regions remains unclear, and no white blood cell count (WBC) intervals exist for Duffy-null individuals. This study aimed to establish and compare Duffy-null ANC and WBC reference intervals across 4 continents. A cross-sectional study was conducted assessing healthy Duffy-null individuals from dedicated cohorts (blood donors in Namibia, Saudi Arabia, and the United Kingdom; primary care patients in the United States) and biobanks (participants from the United Kingdom and the United States). Among 8018 participants (880 from dedicated cohorts and 7138 from biobanks), novel ANC and WBC reference intervals were established (Namibia [ANC, 820/μL to 6370/μL; WBC, 2.51 × 109/L to 9.85 × 109/L]; Saudi Arabia [ANC, 1140/μL to 5290/μL; WBC, 3.72 × 109/L to 10.71 × 109/L]; United Kingdom (ANC, 1185/μL to 5462/μL; WBC, 3.1 × 109/L to 8.8 × 109/L]; the United States [ANC, 1210/μL to 5390/μL; WBC, 3.00 × 109/L to 9.66 × 109/L]), with no significant differences between cohorts. Institutional reference intervals misclassified 27.9% (Namibia), 50.9% (Saudi Arabia), 26.0% (United Kingdom), and 21.7% (the United States) as neutropenic. Biobank analyses confirmed no significant difference in ANC between Black and non-Black Duffy-null participants. Duffy-null individuals consistently exhibit lower ANC and WBC across ethnic groups and regions. Current reference intervals overlook this variation, risking misdiagnosis and health inequities. Implementing Duffy-specific reference intervals is essential for equitable and accurate clinical decisions worldwide.