Neutropenia is seen in 5%–10% of healthy people
Based on absolute neutrophil count, neutropenia is commonly defined as mild (1.0–1.5 × 109/L), moderate (0.5–0.9 × 109/L) or severe (< 0.5 × 109/L).1 However, the reference interval is specific to the population. Mild asymptomatic neutropenia per the above definition is common in people of sub-Saharan African, Arab or West Indian ancestry,2 and is strongly associated with the Duffy-null phenotype of red blood cells that protects against Plasmodium vivax malaria.
Common causes include medications, infection, nutritional deficiency, malignant disease and autoimmune disease
Causes include underproduction (e.g., myelodysplastic syndrome), immune-mediated destruction or redistribution of neutrophils to the endothelium and reticuloendothelial system. Antithyroid, anti-infective and psychotropic drugs, as well as chemotherapy, are causes of drug-induced neutropenia.3,4 Transient neutropenia may occur after acute viral infection and typically resolves within 2 weeks. Joint swelling, rash, bony pain, splenomegaly or lymphadenopathy may suggest malignant or autoimmune disease.
Investigation should begin with a repeat complete blood count and peripheral blood film
Neutropenia is often identified incidentally. Persistent and unexplained neutropenia requires further work-up for a range of causes, including chronic viral infection (e.g., hepatitis, HIV) and nutritional deficiency (e.g., vitamin B12) (Appendix 1, available at www.cmaj.ca/lookup/doi/10.1503/cmaj.220499/tab-related-content).
Treatment of mild neutropenia should be directed at the underlying cause
Patients with mild neutropenia are not at substantially increased risk of infection.5 The neutrophil count should be checked every 3–6 months for at least 1 year to rule out progression to more severe neutropenia.
Patients with moderate-to-severe neutropenia for more than 6 months should be referred to a specialist
Patients with recurrent or severe bacterial infections (e.g., requiring hospital admission or intravenous antibiotics), abnormalities on peripheral blood films (e.g., circulating blasts, hairy cells, large granular lymphocytes, dysplastic granulocytes) or pancytopenia also warrant referral to a specialist (e.g., hematologist, internist, pediatrician).1 Febrile neutropenia (absolute neutrophil count < 0.5 × 109/L and an oral temperature > 38.0°C sustained over 1 h) requires immediate treatment with broad-spectrum antibiotics.
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Footnotes
Competing interests: Siraj Mithoowani has received personal fees from Leo Pharma. Mark Crowther has served on advisory boards for Precision Biologicals, Hemostasis Reference Laboratories and Syneos Health. He has developed educational programs or received speaking fees from Bayer, Pfizer, CSL Behring and Diagnostica Stago. He is also the Leo Pharma Chair in Thromboembolism Research at McMaster University. No other competing interests were declared.
This article has been peer reviewed.
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