Culturally competent care for Canadian children with ‘low’ neutrophil counts

Neutropenia is a common laboratory finding encountered by paediatricians in Canada. Neutropenia is typically defined as an absolute neutrophil count (ANC) below 1,500/μL and is classified as mild (ANC 1,000 to 1,500/μL), moderate (ANC 500 to 1,000/μL), or severe (ANC <500/μL). The finding of moderate or severe neutropenia always requires further investigation; however, the framework for evaluating a child with mild neutropenia is more nuanced. While mild neutropenia can be the presenting manifestation of serious medical conditions, in certain settings, it can also be a normal finding.

A significant number of children may present to paediatric providers with mild neutropenia due to a benign condition associated with the red cell Duffy null (Fya-/Fyb-) phenotype. This phenotype is derived from a benign variant in the Duffy Antigen Receptor for Chemokines (DARC) gene on chromosome 1p22 (1–3). The exact mechanism by which the DARC gene impacts neutrophil counts is not known. Suggested mechanisms include changes in neutrophil margination, release from the bone marrow, and migration into tissues due to alterations in gene regulation and cytokine production (1–3). The Duffy null phenotype is common in individuals with ancestry that can be traced back to sub-Saharan Africa with up to two-thirds of these individuals having the Duffy null phenotype (2). As the Duffy antigen is utilized by the malaria parasite to enter the red blood cell, it has been hypothesized that the positive selection for the null allele may have conferred protection from malaria infection resulting in a survival advantage for individuals with this phenotype (4). The Duffy-null phenotype has also been identified in individuals of Yemenite & Ethiopian Jewish, Arab, Caribbean and West Indian descent (5).

Individuals with ancestry in one of the previously listed regions who were found to have mild neutropenia were historically diagnosed as having ‘benign ethnic neutropenia’. Reports indicate that up to 50% of Africans have a neutrophil count in this range (6–8). When the DARC gene variant responsible for this presentation was identified, the diagnosis ‘Duffy null neutropenia’ was given to many of these patients instead. Both of these terms are problematic as they imply that a common benign phenotype found in non-White populations is abnormal and they turn a normal benign finding into a pathologic diagnosis (5).

While children with the Duffy null phenotype may have a neutrophil count in the range of 1,000 to 1,500/μL, unlike many other children with low neutrophils, they are not at an increased risk of infections or other pathologic conditions. Children with the Duffy null phenotype do not have other cytopenias, splenomegaly, or lymphadenopathy. Given that these children are not at an increased risk of developing a serious infection they do not need any special precautions, monitoring, or evaluation (9–11).

When evaluating a child with mild neutropenia, in the absence of red flags suggesting a pathologic etiology (Table 1), no further evaluation to confirm the presence of a Duffy null phenotype is required. Blood Bank serologic testing for the Duffy antigen or DARC genotyping can be used to confirm suspected Duffy null phenotype for cases where confirming the phenotype may alter care. For example, in titrating drugs known to cause neutropenia, it may be important to know if a patient has the Duffy null phenotype to differentiate between drug induced neutropenia and a normal neutrophil count for a patient with the Duffy null phenotype.

Table 1.

Red flags in the evaluation of a child with neutropenia

Clinical history	-Prolonged or recurrent fevers -Weight loss -Night sweats -Recurrent infections -Oral ulcers
Family history	-Cancer -Immunodeficiency -Autoimmune conditions -Bone marrow failure -Recurrent infections
Physical exam	-Lymphadenopathy -Splenomegaly -Hepatomegaly -Dysmorphic facial features -Numerous congenital anomalies
Laboratory findings	-Additional cytopenias (anemia, thrombocytopenia, lymphopenia) -Elevated MCV -Moderate or severe neutropenia

Canadian children come from a larger number of diverse backgrounds and many Canadian children can trace their ancestry to regions where the Duffy null phenotype is common (12). In order to provide culturally competent care to these children, Canadian child health advocates and practitioners must be committed to eliminating the structural racism that exists within our medical system. We must actively remove the diagnosis of ‘benign ethnic neutropenia’ and ‘Duffy null neutropenia’ from the medical records of patients who were labeled with these terms prior to the medical community understanding that these patients’ neutrophil count is normal for a patient with a Duffy null phenotype. Going forward these diagnoses should not be made; instead families should be counseled that their child’s neutrophil count is normal for a patient with the Duffy null phenotype. In parallel, we must ensure that Canadian healthcare practitioners understand the normal variations in neutrophil numbers based on genotype and the benign nature of these differences. Clear documentation by individuals providing culturally competent care to these children will prevent families from needing to explain this normal variation to providers. In the future, the inclusion of Duffy-null status as a consideration in the development of reference ranges for ANC may play a role in mitigating this issue.

By making these simple changes to the way we think about the care of children with a neutrophil count below the typical reference range, we can demonstrate our commitment to eliminating residual structural racism within our medical system and at the same time provide the highest quality of care to paediatric patients in Canada.

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POTENTIAL CONFLICTS OF INTEREST

All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.