Multinational assessment of absolute neutrophil counts and white blood cell counts among healthy Duffy-null adults
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.
Article Details
Authors (22)
Stephen P. Hibbs
1Wolfson Institute of Population Health, Queen Mary University of London, London, United Kingdom
Israel Chipare
2Blood Transfusion Service of Namibia, Windhoek, Namibia
Amr J. Halawani
3Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Mecca, Saudi Arabia
Sophie E. Legge
Geoffrey Fell
5Department of Data Science, Dana-Farber Cancer Institute, Boston, MA
Daniel Dees
6Department of Pathology, Brigham and Women's Hospital, Boston, MA
David J. Roberts
7NHS Blood and Transplant, Oxford, United Kingdom
Nicholas Gleadall
10Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom
Olga Shamardina
10Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom
Abdulrahman A. Alhamzi
12Department of Blood Bank, King Fahad Central Hospital, Jazan, Saudi Arabia
Edwig Shingenge
13Department of Clinical Health Sciences, Namibia University of Science and Technology, Windhoek, Namibia
Mohammed J. Alabdly
12Department of Blood Bank, King Fahad Central Hospital, Jazan, Saudi Arabia
Hilary T. Charuma
2Blood Transfusion Service of Namibia, Windhoek, Namibia
Mohammed A. Nushaily
12Department of Blood Bank, King Fahad Central Hospital, Jazan, Saudi Arabia
Judith M. Sinvula
2Blood Transfusion Service of Namibia, Windhoek, Namibia
Menelik Russo
13Department of Clinical Health Sciences, Namibia University of Science and Technology, Windhoek, Namibia
Michelle Sholzberg
14Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
Sara Paparini
1Wolfson Institute of Population Health, Queen Mary University of London, London, United Kingdom
Vanessa Apea
1Wolfson Institute of Population Health, Queen Mary University of London, London, United Kingdom
Maureen Okam Achebe
17Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA
Nancy Berliner
1Department of Hematology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
Lauren E. Merz
18Division of Hematology/Oncology, Mass General Brigham, Boston, MA