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Multinational assessment of absolute neutrophil counts and white blood cell counts among healthy Duffy null adults

Hibbs, Stephen P., Chipare, Israel, Halawani, Amr J., Legge, Sophie E., Fell, Geoffrey, Dees, Daniel, Roberts, David J., Gleadall, Nicholas, Shamardina, Olga, Alhamzi, Abdulrahman A., Shingenge, Edwig, Alabdly, Mohammed J., Charuma, Hilary T., Nushaily, Mohammed A., Sinvula, Judith M., Russo, Menelik, Sholzberg, Michelle, Paparini, Sara, Apea, Vanessa, Achebe, Maureen, Berliner, Nancy and Merz, Lauren E. 2025. Multinational assessment of absolute neutrophil counts and white blood cell counts among healthy Duffy null adults. Blood 10.1182/blood.2025029359

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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 four continents. A cross-sectional study was conducted assessing healthy Duffy null individuals from dedicated cohorts (blood donors in Namibia, Saudi Arabia, and the UK; primary care patients in the USA) and biobanks (participants from the UK and USA). Reference intervals were determined using Clinical & Laboratory Standards Institute guidelines. Among 8,018 participants (880 from dedicated cohorts, 7,138 from biobanks), novel ANC and WBC reference intervals were established: Namibia (820–6,370/μL; 2.51–9.85× 109/L), Saudi Arabia (1,140–5,290/μL; 3.72–10.71× 109/L), UK (1,185–5,462/μL; 3.1–8.8× 109/L) and the USA (1,210–5,390/μL; 3.00-9.66× 109/L), with no significant differences between cohorts. Institutional reference intervals misclassified 27.9% (Namibia), 50.9% (Saudi Arabia), 26.0% (UK) and 21.7% (USA) 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.

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: Schools > Medicine
Additional Information: License information from Publisher: LICENSE 1: Title: This article is under embargo with an end date yet to be finalised. RSS applied 19/11/2025 AB
Publisher: American Society of Hematology (ASH Publications)
ISSN: 0006-4971
Date of First Compliant Deposit: 19 November 2025
Date of Acceptance: 16 October 2025
Last Modified: 20 Nov 2025 11:00
URI: https://orca.cardiff.ac.uk/id/eprint/182389

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