New Blood Reference Ranges Standardize Care for Duffy-Null Individuals

New Blood Reference Ranges Standardize Care for Duffy-Null Individuals

For more than 66% of people with African or Mediterranean ancestry in the United States, a common genetic trait has long been a source of unnecessary medical anxiety. Individuals with Duffy-null status—a genetic adaptation that provides protection against malaria—naturally possess lower circulating white blood cell counts. For decades, standard laboratory reference ranges failed to account for this biological reality, often flagging these healthy individuals as having neutropenia. This misclassification has frequently triggered a cascade of clinical errors, including unnecessary bone marrow biopsies, the exclusion of patients from vital clinical trials, and the premature discontinuation of life-saving therapies like chemotherapy.

To correct this systemic oversight, the American Society of Hematology (ASH) has officially established the first standardized, personalized reference ranges for children and adults with Duffy-null status. These new guidelines, published in Blood Advances, provide clinicians with a clear, evidence-based framework to distinguish between normal physiological variations and actual clinical illness. By replacing generalized, outdated metrics with these tailored ranges, the medical community aims to eliminate the diagnostic confusion that has historically burdened this demographic.

The Genetic Logic Behind the Numbers

The Duffy antigen is a protein found on the surface of red blood cells. Over thousands of years, populations in regions where malaria is endemic evolved to lose this protein, as it serves as an entry point for malaria parasites. This evolutionary defense mechanism, however, carries a physiological trade-off: it alters the distribution of neutrophils, the most common type of white blood cell. In Duffy-null individuals, neutrophils are more heavily concentrated in the body’s tissues rather than circulating in the blood, where standard laboratory draws occur. Consequently, a routine blood test—which measures circulating cells—will consistently show lower counts for these individuals compared to those who are Duffy-positive.

Researchers involved in the ANC by Duffy Status Project validated these new reference ranges by collecting 1,412 samples from Duffy-null individuals across 23 sites in the United States. The data established specific thresholds for absolute neutrophil counts (ANC) and total white blood cell (WBC) counts across four age categories. 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, highlighted the necessity of connecting biological findings with direct patient care.

According to Dr. Achebe, while medical professionals have long recognized Duffy-null status, this understanding has yet to be effectively integrated into routine clinical operations. She noted that these reference ranges provide a practical, actionable method to accurately identify baseline health in Duffy-null patients, thereby preventing redundant medical procedures, exclusions from trials, and limitations on medication.

Validated Ranges for Clinical Implementation

The established ranges now provide a clear, age-appropriate guide for healthcare providers to reference when interpreting laboratory results for Duffy-null patients:

New Hematology Ranges Address Health Equity

The new ranges move the hematology sector closer to health equity. The establishment of these values addresses a critical concern where patients were frequently told that something was wrong despite having no underlying health issues. ASH President Robert Negrin, MD, noted that this initiative is designed to make a lasting impact by empowering both healthcare systems and individual patients.

While the new ranges cover the majority of the population, researchers noted that further study is required to understand the reference intervals for children under 6 months old. Despite the variation in collection strategies and patient populations across the 23 research sites, the consistency of the findings suggests that these ranges are robust enough for widespread clinical adoption. ASH has also published research in Blood Advances indicating that universal pediatric testing for the Duffy-null variant is cost-effective, further strengthening the case for proactive documentation of this status in electronic health records.

For patients, the recommendation is clear: knowing one’s Duffy status can serve as a powerful tool for health advocacy. Because Duffy-null status is not a disease, experts encourage individuals to discuss the testing process with their physicians and ensure that their status is formally coded in their medical records. This simple documentation can prevent the misinterpretation of future blood work and ensure that treatment plans—particularly for those undergoing chemotherapy or participating in clinical trials—are based on accurate physiological data.