Low White Blood Cell Count in Black Adults: What It Means

If a routine blood test came back saying your white blood cell count or your neutrophil count is low, and no one could tell you why, there is a common and well-documented explanation that many clinicians still do not raise. It is called Duffy-null associated neutrophil count, and until recently it was called benign ethnic neutropenia. It is not an illness. It does not need treating. What it does need is recognising, because the treatments people lose over it are real.

The Duffy antigen sits on the surface of red blood cells and is encoded by a gene called ACKR1, formerly DARC. A variant common in people of African ancestry switches off the antigen's expression on red cells. It became common because it offers protection against one form of malaria, Plasmodium vivax, which historically could not enter red cells without that receptor.

One downstream effect is that fewer neutrophils circulate in the bloodstream at any moment. They still exist and still work, they are simply distributed differently, sitting in tissue and marrow rather than in the blood being sampled. A genome-wide study of 16,388 African American participants confirmed the variant as the main driver of lower total white blood cell and neutrophil counts in people of African descent.

The name changed for a reason. "Benign ethnic neutropenia" described a normal finding as a disorder and attached it to ethnicity rather than to the gene actually responsible. Researchers who documented the phenotype argued for replacing it with Duffy-null associated neutrophil count, and the newer literature uses that term.

A study at Brigham and Women's Hospital tested Duffy status alongside blood counts in a healthy population of self-identified Black patients at a single primary care centre. Two thirds, 80 of 120, had the Duffy-null phenotype. Their median absolute neutrophil count was 2,820 cells per microlitre, against 5,005 in the Duffy non-null patients in the same group. Nearly a quarter of the Duffy-null group, 19 of 80, had a count below 2,000, the threshold most laboratories flag. None of the Duffy non-null patients did.

A 2026 study went further and built reference intervals specifically for Duffy-null patients from 122 healthy individuals with confirmed phenotype. The 95% reference interval for absolute neutrophil count came out at 1,010 to 4,340 cells per microlitre. The lower bound sits below the standard neutropenia cutoff. In other words, a count that reads as abnormal against the reference range printed on your lab report can be squarely normal for you.

This would be a footnote if the number were only a number. It is not, because absolute neutrophil count is used as a gate on treatment in three places.

Cancer treatment and trials

Researchers examined contemporary phase 3 cancer trials for the five most common cancers in the US and UK, and the standard chemotherapy regimens recommended by national guidelines. 221 of 289 eligible trials, 76.5%, excluded patients with a neutrophil count inside the Duffy-null reference range. Among 71 standard regimens, 38 called for a dose reduction at counts within that same range. For trials testing cytotoxic chemotherapy the exclusion rate was 81.7%.

The clinical consequence has been measured. In a review of 493 breast cancer patients at a referral centre, the 72 with Duffy-null associated counts had significantly more treatment delays and discontinuations, and prophylactic filgrastim did not reduce them. Only one of those 72 developed neutropenic fever, and there was no effect on overall or progression-free survival. The treatment was being interrupted over a number that was never dangerous.

Clozapine

Clozapine is the most effective medication for treatment-resistant schizophrenia and the only one licensed for it. Because it can rarely cause severe neutropenia, it has always carried blood-count monitoring, and a baseline count below threshold has kept people off it entirely. The FDA removed the clozapine REMS programme in 2025, so prescribers no longer have to enrol patients or report counts to a central system, though the monitoring guidance and the boxed warning remain in the label. The UK's pharmacogenomics centre published a guideline in 2026 for ACKR1 Duffy-null genotype testing specifically to stop this phenotype from blocking clozapine.

Other medicines with count-based rules

The same logic reaches azathioprine and methotrexate, used in inflammatory bowel disease and autoimmune conditions, where dosing is adjusted on neutrophil count. And a 2026 study found Duffy-null testing is underused in the workup of neutropenia in children and young adults, which means the same child can be put through repeated blood tests, and sometimes a bone marrow biopsy, for a normal variant.

If you have been told your white cell or neutrophil count is low:

• Ask whether it has ever been explained. A count that has been stable and low for years, with no infections, no fevers and no other blood abnormality, looks very different from a count that has recently dropped.
• Ask whether Duffy-null associated neutrophil count has been considered. Naming it is often enough. Duffy phenotyping is a standard red cell test that blood banks already run, and ACKR1 genotyping is available.
• Ask before treatment is changed. If a chemotherapy dose is being reduced, a cycle delayed, a trial closed to you, or clozapine ruled out on a count alone, that is the moment to ask whether your baseline has been established rather than assumed.
• Ask for it to be written in your record, so the next clinician who sees the number does not restart the investigation.

You should not have to teach your own doctor the literature on your own blood. If explaining it has not worked, it is reasonable to want a second opinion from someone who starts from the same page. You can find a Black clinician in our directory by specialty and city. If cost is the obstacle, a community health center charges on a sliding scale set by your income and cannot turn you away for inability to pay.