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 and assess severity, followed by a thorough history, physical examination, and laboratory testing to determine the underlying cause and guide management. The initial evaluation should include a thorough history focusing on medication use, recent infections, family history, and systemic symptoms, as well as a physical examination to look for signs of infection, lymphadenopathy, hepatosplenomegaly, and other abnormalities 1. Laboratory testing should include a peripheral blood smear, comprehensive metabolic panel, vitamin B12 and folate levels, and inflammatory markers like ESR and CRP.

Key Components of the Workup

• A complete blood count with differential to confirm the diagnosis and assess severity
• Thorough history and physical examination to identify potential causes and signs of infection
• Laboratory testing, including peripheral blood smear, comprehensive metabolic panel, and inflammatory markers
• Risk stratification according to susceptibility to infection, with high-risk patients being those with anticipated prolonged and profound neutropenia or a Multinational Association for Supportive Care (MASCC) score of <21 1

Management

Management depends on the underlying cause and severity, ranging from observation for mild cases to granulocyte colony-stimulating factors (G-CSF) like filgrastim (5-10 μg/kg/day subcutaneously) for severe neutropenia. Patients with febrile neutropenia require urgent evaluation, blood cultures, and broad-spectrum antibiotics (such as piperacillin-tazobactam 4.5g IV every 6 hours or cefepime 2g IV every 8 hours) 1. The use of G-CSF should be guided by the risk of febrile neutropenia and the severity of neutropenia, with primary prophylaxis indicated for patients at high risk of febrile neutropenia.

Special Considerations

Special consideration should be given to patients with severe, persistent, or unexplained neutropenia, who may require bone marrow aspiration and biopsy to evaluate for primary bone marrow disorders. Additional testing may include autoimmune markers (ANA, rheumatoid factor), HIV testing, and specific genetic testing if congenital neutropenia is suspected. The workup is essential because neutropenia increases infection risk, with risk being highest when the absolute neutrophil count falls below 500/mm³, at which point prophylactic measures may be necessary.

From the Research

Definition and Classification of Neutropenia

• Neutropenia is defined as an absolute neutrophil count (ANC) of less than 1,500/mcL or <1.5 × 10(9)/L 2, 3, 4, 5
• It can be classified as mild (1000-1500 cells/mm(3)), moderate (500-1000 cells/mm(3)), or severe (<500 cells/mm(3)) 3
• Neutropenia can be transient or chronic, with chronic neutropenia further described as extrinsic or intrinsic 2

Etiology and Pathogenesis

• Neutropenia can develop as a result of one or more pathologic mechanisms, including decreased bone marrow production, sequestering of neutrophils, and increased destruction of neutrophils in the peripheral blood 3
• The clinical result is an increased risk for infection, which is directly proportional to the severity and duration of neutropenia 3

Clinical Approach to Diagnosis and Treatment

• Evaluation of patients with neutropenia should be guided by the severity of presentation, duration of leukopenia, and clinical status of the patient 2
• Assessment of patients with neutropenia should include confirmation of neutropenia, examination of a blood smear, and a careful review of the patient's medical history, family history, and physical examination 6
• Patients with febrile neutropenia should undergo treatment with antibiotics, and other treatments should be aimed at management of the underlying cause of neutropenia 2, 4
• 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) 4, 5

Diagnostic Evaluation

• Laboratory evaluation generally includes repeat complete blood cell counts (CBCs) with differentials and bone marrow examination with cytogenetics 5
• Neutrophil antibody testing may be useful but only in the context of clinical and bone marrow findings 5
• Examination of a bone marrow aspirate and/or biopsy and cytogenetic testing are primary for diagnostic evaluation 6