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.

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Journal
Blood Advances
Published
2026-11-05
DOI
https://doi.org/10.1182/bloodadvances.2026020900
Primary Topic
Clinical Laboratory Practices and Quality Control
Type
article
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article

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

Ivo M.B. Francischetti, Victoria Forbes, Nicole Kucine, Matthew S. Karafin et al.
Blood Advances
Clinical Laboratory Practices and Quality Control
article

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

Ivo M.B. Francischetti, Victoria Forbes, Nicole Kucine, Matthew S. Karafin, Charlotte McIlwaine Story, Alexa J. Siddon, George Goshua, Vivian Y. Chang, Lauren E. Merz, Eric Burks, Jennifer M. Jones, Patrick T. McGann, Sabrina Racine‐Brzostek, Michael Blechner, Karishma Vijay Rupani, Zhen W. Mei, Abraham Haimed, Don Ambrose Stevens, Richard Curtis Godby, Priyadarshini Kumar, Michael R. Lewis, Geling Li, Corinna L. Schultz, Justin Eddie Juskewitch, Emmanuel A. Fadeyi, Alexis A. Thompson, Aliza K. Fink, Warren Benjamin Fingrut, Peng Ji, David Levitz, James M. Szymanski, Kelly J. Walkovich, Cecelia L. Calhoun, Elizabeth P. Crowe, Rahma M. Warsame, Angela C. Weyand, Hyojeong Han, Margarita Kushnir, Maureen Achebe, Johnson M. Liu, Nibal Zaghloul, Lucy A. Godley, Nathalie van Havre, Linda Song, Adam C. Cuker, Patricia Frustace, John Mark Sloan, Samuel Wilson, Sally A. Campbell‐Lee, Cyril Jacquot, Chibuzo Ilonze, Richard L. Haspel, Amy C. Soni, Christina M. Barriteau, Christine N. Sillings, Stella T. Chou, Christian P. Nixon, Clifford M. Takemoto, VK Gadi, Gilles Attipoe, Gary Rose, Jamie Tyson, Yadashe Belay, Taylor A. Van Denakker
article en

Abstract

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.

Blood Advances
Boston University (US), Northwestern University (US), University of North Carolina at Chapel Hill (US), Brigham and Women's Hospital (US), Lurie Children's Hospital (US), St. Jude Children's Research Hospital (US), Beth Israel Deaconess Medical Center (US), Mayo Clinic (US), Montefiore Medical Center (US), Children's Hospital of Philadelphia (US), Children's National (US), Saint Peter's University Hospital (US), The University of Texas MD Anderson Cancer Center (US), Harvard University (US), Johns Hopkins University (US), University of California, Los Angeles (US), University of Alabama (US), Norton Healthcare (US), Brown University (US), University of Michigan (US), American Society of Hematology (US), University of Alabama at Birmingham (US), Yale University (US), University of Illinois Chicago (US), Levine Cancer Institute (US), Weill Cornell Medicine (US), Banner MD Anderson Cancer Center (US), Dartmouth Health (US), Wake Forest University Health Sciences (US), Wake Forest University (US), UConn Health (US), University of Pennsylvania (US), Icahn School of Medicine at Mount Sinai (US)
Openalex Percentile: Top 9%
Clinical Laboratory Practices and Quality Control
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