What is the workup for neutropenia (low neutrophil count)?

From the Guidelines

The workup for neutropenia should begin with a complete blood count with differential to confirm the diagnosis (absolute neutrophil count <1500/mm³) and assess severity. Initial evaluation includes a thorough history focusing on medication use, recent infections, family history, and systemic symptoms. Physical examination should look for signs of infection, lymphadenopathy, hepatosplenomegaly, and other abnormalities. Laboratory testing should include a peripheral blood smear, comprehensive metabolic panel, vitamin B12 and folate levels, and inflammatory markers like ESR and CRP. Bone marrow aspiration and biopsy are indicated for severe, persistent, or unexplained neutropenia to evaluate for hematologic malignancies or bone marrow failure. Additional testing may include autoimmune markers (ANA, rheumatoid factor), HIV testing, and specialized tests like flow cytometry or genetic testing depending on clinical suspicion. Management depends on the underlying cause, with treatment of infections, discontinuation of offending medications, or specific therapies for identified conditions. In severe neutropenia (ANC <500/mm³), prophylactic antibiotics and granulocyte colony-stimulating factors like filgrastim (5-10 μg/kg/day subcutaneously) may be considered, as supported by recent guidelines 1. This systematic approach helps identify the cause of neutropenia, which can range from benign ethnic variations to serious conditions requiring prompt intervention.

Key Considerations

• The most recent and highest quality study on the topic is from 2017, which provides guidance on the management of myelodysplastic syndromes, including the use of erythropoiesis-stimulating agents (ESAs) and granulocyte colony-stimulating factors (G-CSF) in patients with lower-risk disease 1.
• The use of G-CSF in combination with ESAs has been shown to have synergistic erythropoietic activity and can enhance the erythroid response rates in patients with myelodysplastic syndromes 1.
• The NCCN Guidelines recommend stratifying patients with lower-risk myelodysplastic syndromes into several groups based on their clinical characteristics and cytogenetic abnormalities, and provide guidance on the use of lenalidomide, ESAs, and G-CSF in these patients 1.

Laboratory Testing

• A complete blood count with differential is essential for confirming the diagnosis of neutropenia and assessing its severity.
• Additional laboratory tests, such as a peripheral blood smear, comprehensive metabolic panel, vitamin B12 and folate levels, and inflammatory markers like ESR and CRP, can help identify underlying causes of neutropenia.
• Bone marrow aspiration and biopsy may be necessary for severe, persistent, or unexplained neutropenia to evaluate for hematologic malignancies or bone marrow failure.

Management

• Management of neutropenia depends on the underlying cause, with treatment of infections, discontinuation of offending medications, or specific therapies for identified conditions.
• In severe neutropenia (ANC <500/mm³), prophylactic antibiotics and granulocyte colony-stimulating factors like filgrastim (5-10 μg/kg/day subcutaneously) may be considered, as supported by recent guidelines 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Neutropenia Workup

The workup for neutropenia, a condition characterized by an abnormally low number of neutrophils in the bloodstream, involves several steps:

• Diagnosis: Neutropenia is typically diagnosed through a complete blood count (CBC) test, which measures the levels of different blood cells, including neutrophils 2, 3, 4, 5.
• Classification: Neutropenia can be classified as transient or chronic, with chronic neutropenia further divided into extrinsic or intrinsic causes 5.
• Assessment: The assessment of patients with neutropenia should be guided by the severity of the condition, duration of leukopenia, and clinical status of the patient 5.
• Risk evaluation: Patients with neutropenia are at risk of developing life-threatening bacterial infections, and the risk of febrile neutropenia should be assessed systematically 3, 5.

Diagnostic Tests

Diagnostic tests for neutropenia may include:

• Complete blood count (CBC) test: This test measures the levels of different blood cells, including neutrophils 2, 3, 4, 5.
• Multi-spectral deep-UV microscopy: This is a label-free technique that can detect and grade neutropenia based on the analysis of live, unstained blood cells in a smear 2.
• Germline and/or somatic mutational analyses: These tests can help characterize and risk-stratify patients with chronic neutropenias 6.

Treatment

Treatment for neutropenia depends on the underlying cause and severity of the condition:

• Antibiotics: Patients with febrile neutropenia should undergo treatment with antibiotics 3, 5.
• Myeloid growth factors: Patients with severe chronic neutropenia may be treated with granulocyte colony-stimulating factor (G-CSF) 3, 6.
• Management of underlying cause: Treatment should also aim to manage the underlying cause of neutropenia, such as viral infections or hematological malignancies 4, 5.