New Reference Ranges Clarify Normal Neutrophil Counts in Duffy-Null Patients

Duffy-null status is a common genetic trait associated with naturally lower circulating white blood cell counts. It affects about 10% of the U.S. population and more than 66% of people with African or Mediterranean ancestry in the U.S. When standard laboratory reference ranges are applied, these individuals may be incorrectly classified as having neutropenia, potentially leading to unnecessary testing or treatment changes. To reduce this risk of misclassification, researchers now report personalized reference ranges for children and adults with Duffy-null status.

The American Society of Hematology (ASH) developed the new reference ranges through the ANC by Duffy Status Project. The Duffy antigen is a protein found on red blood cells, and individuals who lack it are considered Duffy-null. This status affects neutrophil distribution, with more neutrophils concentrated in tissues and fewer circulating in the blood, where laboratory testing measures white blood cell and neutrophil counts.

Researchers across 23 sites in the U.S. collected 1,412 samples from Duffy-null individuals. The study validated adult reference ranges and generated the first pediatric data across four age groups. The ranges were based on absolute neutrophil count (ANC), which measures the number of neutrophils in blood, and white blood cell count (WBC), which measures the total number of circulating white blood cells.

For adults, the ANC reference range was 1.03 to 7.30×10^9/L and the WBC range was 3.0 to 10.7×10^9/L. Among children, ANC and WBC ranges were 0.53 to 4.50×10^9/L and 4.4 to 12.6×10^9/L for ages 6 months to 2 years; 0.78 to 4.67×10^9/L and 3.8 to 10.8×10^9/L for ages 3 to 6 years; 0.87 to 5.34×10^9/L and 2.9 to 10.1×10^9/L for ages 7 to 12 years; and 0.90 to 4.89×10^9/L and 3.1 to 9.2×10^9/L for ages 13 to 17 years. The findings were published in Blood Advances.

The study found no meaningful differences in the reference ranges after accounting for variation in collection strategies and patient populations across participating sites. Further research is needed to establish reference intervals for children younger than 6 months. ASH also published a separate study in *Blood Advances* indicating that universal pediatric testing for the Duffy-null variant is cost-effective.

“This is a significant step for individuals with Duffy-null status, who are often told that something is wrong, even when there are no problems with their health. The establishment of these reference ranges addresses a critical health equity concern that has long been needed and will make a lasting impact on the lives of individuals with Duffy-null status,” said Robert Negrin, MD, ASH President.

“Although clinicians have long been aware of Duffy-null status, this knowledge has not yet translated into clinical practice. These reference ranges mark a concrete, implementable step for making it easier to recognize what is normal for Duffy-null individuals to avoid unnecessary testing, clinical trial exclusions, and medication restrictions,” said Maureen Achebe, MD, MPH, clinical director of hematology services at Brigham and Women’s Hospital and Dana Farber Cancer Institute and associate professor of medicine and global health equity at Harvard Medical School.

Related Links
American Society of Hematology