Researchers working through an American Society of Hematology initiative have established personalized laboratory reference ranges for children and adults with Duffy-null status, publishing the newly defined metrics in Blood Advances to assist clinicians in accurately distinguishing normal blood counts from abnormal values.
To validate the adult metrics and assemble the first baseline data for pediatric care, investigators collected 1,412 blood samples from individuals with Duffy-null status across 23 participating study sites located throughout the United States.
The evaluation focused on two standard measures: absolute neutrophil count, representing the quantity of neutrophils circulating in the blood, and total white blood cell count. For adults with Duffy-null status, the researchers defined reference intervals of 1.03 to 7.30×10⁹/L for absolute neutrophil count and 3.0 to 10.7×10⁹/L for total white blood cell count. For infants and toddlers aged 6 months to 2 years, the corresponding ranges were established as 0.53 to 4.50×10⁹/L for neutrophil count and 4.4 to 12.6×10⁹/L for total white blood cells.
Across older pediatric cohorts, the study established age-specific ranges spanning three additional developmental categories. Children aged 3 to 6 years presented reference ranges of 0.78 to 4.67×10⁹/L for absolute neutrophil count and 3.8 to 10.8×10⁹/L for total white blood cells. For children aged 7 to 12 years, the intervals were established at 0.87 to 5.34×10⁹/L for neutrophils and 2.9 to 10.1×10⁹/L for white blood cells, while adolescents aged 13 to 17 years demonstrated expected values of 0.90 to 4.89×10⁹/L for neutrophils and 3.1 to 9.2×10⁹/L for total white blood cell counts.
Investigators reported that despite variation in patient demographics and sample collection strategies across the 23 clinical sites, no meaningful differences emerged among the resulting reference intervals after accounting for those operational factors. The authors highlighted an ongoing research limitation, noting that additional investigation remains necessary to determine expected laboratory values for infants younger than 6 months of age.
Duffy-null status is a benign genetic trait rather than an active illness, defined by the natural absence of the Duffy antigen protein on red blood cells. The evolutionary loss of this antigen developed over thousands of years in malaria-endemic regions such as Africa and the Mediterranean, where absence of the protein serves as a biological defense against infection by malaria parasites. In the United States, this genetic trait is present in more than 66 percent of individuals who have African or Mediterranean ancestry.
The presence or absence of the Duffy antigen directly influences how neutrophils, the most common type of infection-fighting white blood cell, are partitioned throughout the human body. In individuals with Duffy-null status, neutrophils concentrate in higher proportions within body tissues rather than in the bloodstream where diagnostic blood draws take place.
This recurring misinterpretation has historically triggered invasive follow-up evaluations such as bone marrow biopsies, inappropriate exclusions from investigational clinical trials, and unwarranted interruptions of essential medical treatments, including chemotherapy regimens.
Study author Maureen Achebe, clinical director of hematology services at Brigham and Women’s Hospital and Dana-Farber Cancer Institute, emphasized that while the medical community has long recognized the biological existence of Duffy-null status, that understanding had failed to translate into everyday clinical decision-making. According to study leadership, formalizing these reference values provides a practical clinical tool to avert misdiagnoses and prevent unwarranted restrictions on therapeutic care.
Addressing the broader epidemiological scope of the initiative, project leaders emphasized that establishing these personalized reference ranges holds direct relevance for roughly ten percent of the overall United States population. Clinical experts involved in the national effort noted that establishing tailored reference intervals represents the first formal framework of its kind, offering clinical teams concrete benchmarks to determine accurately whether observed white blood cell counts represent normal physiological variation or genuine pathological abnormalities, thereby avoiding extensive rounds of unneeded diagnostic testing.
Dr. Negrin pointed out that individuals with Duffy-null status have routinely faced clinical encounters where they were told that something was wrong, even when there were no problems with their health. The establishment of these reference ranges, Dr. Negrin observed, directly addresses a critical and long-needed health equity concern within modern medicine, creating a structural clinical advance that will make a lasting positive impact on the lives, routine medical evaluations, and general care of individuals who carry Duffy-null status.
The diagnostic ambiguities surrounding Duffy-null status carry severe clinical consequences when low circulating white blood cell counts are mistakenly interpreted as indicators of serious underlying conditions. In standard clinical environments, laboratory assessments that record lower absolute neutrophil counts and reduced overall white blood cell concentrations can be wrongly perceived as signals for illnesses such as active infections or cancer. These misunderstandings can directly trigger invasive diagnostic procedures, including unnecessary bone marrow biopsies, inappropriate exclusions from investigational clinical trials, or the abrupt discontinuation of necessary medical therapies such as ongoing chemotherapy treatments.
To prevent these adverse clinical outcomes, the study authors emphasize direct patient awareness and proactive self-advocacy across all stages of individual healthcare interactions. Duffy-null status is not an illness or disease, but a benign genetic variant associated with lower concentrations of white blood cells circulating within the bloodstream. Because an individual’s Duffy status can be definitively determined through a simple blood test, clinicians and investigators encourage everyone to discuss getting tested with their healthcare providers. Understanding one’s Duffy status equips patients to advocate effectively for appropriate care throughout their healthcare journey, ensuring that future diagnostic findings are evaluated with full awareness of their underlying genetic background.
Beyond initial testing, the project encourages individuals who have Duffy-null status to share this information actively with their healthcare providers and request that it be formally captured in their health records. By utilizing dedicated diagnostic codes to document Duffy-null status within electronic medical files, patients and clinicians can ensure that this physiological trait is explicitly recognized during clinical decision-making.
These clinical and educational objectives are organized under the broader ANC by Duffy Status Project, a collaborative national initiative established by the American Society of Hematology with support from the Doris Duke Foundation. The project aims to improve overall care for individuals with Duffy-null status by redefining reference ranges, empowering healthcare systems, educating healthcare professionals, and advancing systemic interventions across medical institutions.
As part of this comprehensive initiative, the American Society of Hematology also published a companion study in Blood Advances demonstrating that universal pediatric testing for the Duffy-null variant is cost-effective. By establishing the economic and clinical viability of universal screening in children, the companion study makes a compelling case for testing and documenting Duffy status for all pediatric patients early in life.
Founded in 1958, the American Society of Hematology represents the world’s largest professional society of hematologists, dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. Through decades of promoting basic and translational research, patient care, professional education, and healthcare advocacy, the organization has guided the evolution of hematology as a clinical discipline.
Subject of Research: Blood cell count reference ranges for individuals with Duffy-null status
Article Title: ASH project defines critical blood marker ranges for 10% of US population
Article References: ASH project defines critical blood marker ranges for 10% of US population. Original publication (Bibliographic details unavailable.)
Image Credits: AI Generated
DOI: Not provided
Keywords: Duffy-null status, absolute neutrophil count, white blood cell count, reference ranges, American Society of Hematology, neutropenia, Duffy antigen, Blood Advances, health equity, pediatric reference ranges, malaria protection, bone marrow biopsy, chemotherapy interruption, clinical trial exclusion, ANC by Duffy Status Project, Doris Duke Foundation, Robert Negrin, Maureen Achebe
News Source: Ophelia Keating. (November 14, 2026). New Reference Ranges Define Normal Blood Counts for Duffy-Null Status. Scienmag.
