Evaluation and Management of Patients With Isolated Neutropenia

doi:10.1053/j.seminhematol.2013.06.010

Seminars in Hematology

Volume 50, Issue 3, July 2013, Pages 198-206

https://doi.org/10.1053/j.seminhematol.2013.06.010 Get rights and content

Neutropenia, defined as an absolute neutrophil count (ANC) <1.5 × 10⁹/L, encompasses a wide range of diagnoses, from normal variants to life-threatening acquired and congenital disorders. This review addresses the diagnosis and management of isolated neutropenia, not multiple cytopenias due to splenomegaly, bone marrow replacement, or myelosuppression by chemotherapy or radiation. Laboratory evaluation generally includes repeat complete blood cell counts (CBCs) with differentials and bone marrow examination with cytogenetics. Neutrophil antibody testing may be useful but only in the context of clinical and bone marrow findings. The discovery of genes responsible for congenital neutropenias now permits genetic diagnosis in many cases. Management of severe chronic neutropenia includes commonsense precautions to avoid infection, aggressive treatment of bacterial or fungal infections, and administration of granulocyte colony-stimulating factor (G-CSF). Patients with severe chronic neutropenia, particularly those who respond poorly to G-CSF, have a risk of eventually developing myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) and require monitoring for this complication, which also can occur without G-CSF therapy. Patients with cyclic, idiopathic, and autoimmune neutropenia have virtually no risk of evolving to MDS or AML. Hematopoietic stem cell transplantation is a curative therapy for congenital neutropenia with MDS/AML or with cytogenetic abnormalities indicating impending conversion.

Section snippets

Classification Of Neutropenia

Neutropenia can be described as transient (or “acute”) or chronic (or “persistent”); extrinsic or intrinsic; by descriptive names (eg, neonatal isoimmune neutropenia of infancy, cyclic neutropenia, severe congenital neutropenia) and as syndromes (eg, Kostmann, Shwachman-Diamond, and Barth syndromes). The discovery of the diverse causes for the congenital neutropenias now permits genetic diagnosis in many cases.

Nutritional Neutropenias

Nutritional deficiencies of vitamin B₁₂, folic acid, or copper, or severe protein-calorie malnutrition can cause neutropenia. These deficiencies almost always cause multiple cytopenias rather than isolated neutropenia and are usually diagnosed based on medical history, physical examination, and laboratory measurements of specific vitamin levels.

Immune and Autoimmune Neutropenias

Neonatal isoimmune neutropenia occurs in newborns with fetal/maternal neutrophil antigen incompatibility, leading to transplacental transfer of

Complete Blood Cell Count

Neutropenia is usually discovered with a CBC and leukocyte differential count (Diff), done either as a part of evaluation of a patient for acute or recurrent fever and infection, or as part of a general health examination. In a patient with mild neutropenia and no other health or hematologic problems, a follow-up CBC and Diff may be all that is necessary. The medical history and the severity of neutropenia with the initial counts generally direct further evaluation. Every opportunity should be

Acute Infections

Fever in the setting of profound neutropenia is a medical emergency requiring immediate treatment with broad-spectrum antibiotics. Patients with an ANC of 0.2 × 10⁹/L or less almost invariably require hospital admission for intravenous antibiotics, with the choice of drugs depending on local community and/or hospital flora and antibiotic sensitivities. Importantly, antibiotic therapy should include anaerobic coverage when fever is accompanied by abdominal pain, as may recur frequently in cyclic

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: Supported in part by National Institutes of Health Grants No. R01DK054369 and R24AI049393.

: Financial disclosures/conflicts of interest: P.E.N.: none; D.C.D.: consultant and receives research support from Amgen, Thousand Oaks, CA.

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Evaluation and Management of Patients With Isolated Neutropenia

Section snippets

Classification Of Neutropenia

Nutritional Neutropenias

Immune and Autoimmune Neutropenias

Complete Blood Cell Count

Acute Infections

Virus Res

Blood

Support Cancer Ther

Blood

Transfus Med Rev

Blood

Blood

Blood

Blood

Blood

Blood

Blood

ASH Annual Meeting Abstracts

Blood (ASH Annual Meeting Abstracts)

Blood

Blood

ASH Annual Meeting Abstracts

Prevalence of neutropenia in the U.S. population: age, sex, smoking status, and ethnic differences

Ann Intern Med

Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene

PLoS Genet

Application of time series analysis to serial blood neutrophil counts in normal individuals and patients receiving cyclophosphamide

Br J Haematol

Neutropenia and neutrophilia

The phagocyte system and disorders of granulopoiesis and granulocyte function

Infectious etiologies of transient neutropenia in previously healthy children

Pediatr Infect Dis J