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 identify the underlying cause and guide appropriate treatment. The initial evaluation should include a thorough history focusing on medication use, recent infections, family history, and systemic symptoms 1. 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.

Key Components of the Workup

• A complete blood count with differential to confirm the diagnosis and assess severity
• A thorough history focusing on medication use, recent infections, family history, and systemic symptoms
• Physical examination to look for signs of infection, lymphadenopathy, hepatosplenomegaly, and other abnormalities
• Laboratory testing, including 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 underlying hematologic disorders 1.

Management and Treatment

Additional testing may include autoimmune markers (ANA, rheumatoid factor), HIV testing, and specific genetic testing if congenital neutropenia is suspected. Management depends on the underlying cause, with treatment of infections, discontinuation of offending medications, or specific therapies like granulocyte colony-stimulating factor (G-CSF) for certain conditions. Severe neutropenia (ANC <500/mm³) requires prompt evaluation and may necessitate empiric antibiotic therapy if infection is suspected 1. This systematic approach helps identify whether neutropenia is due to decreased production, increased destruction, or abnormal distribution of neutrophils, guiding appropriate treatment.

Risk Stratification

Risk-stratify patients with fever and neutropenia according to susceptibility to infection: high-risk patients are those with anticipated prolonged (>7 days) and profound neutropenia (absolute neutrophil count [ANC] <100 cells/µL) or with a Multinational Association for Supportive Care (MASCC) score of <21; low-risk patients are those with anticipated brief (<7 days) periods of neutropenia and few comorbidities or with a MASCC score of ≥21 1.

Determining the Extent of Infection

Determine the extent of infection through a thorough physical examination, blood cultures, chest radiograph, and additional imaging (including chest CT) as indicated by clinical signs and symptoms 1.

From the Research

Diagnosis and Treatment of Neutropenia

• Neutropenia is defined as an absolute neutrophil count (ANC) of less than 1.5 × 10(9)/L, and severe neutropenia is an ANC of less than 0.5 × 10(9)/L 2, 3.
• The diagnosis and management of neutropenia involve a stepwise approach, focusing on reaching a provisional diagnosis and treatment plan, and then proceeding to a final diagnosis 2.
• Patients with acute febrile neutropenia should be treated with antibiotics, and those at high risk of severe neutropenia should be treated prophylactically with a myeloid growth factor, usually granulocyte colony-stimulating factor (G-CSF) 2, 4.

Classification and Assessment of Neutropenia

• Neutropenia can be classified as transient or chronic, and chronic neutropenia can be further described as extrinsic or intrinsic 3.
• Assessment of patients with neutropenia should be guided by the severity of presentation, duration of leukopenia, and clinical status of the patient 3.
• The risk of febrile neutropenia should be assessed systematically in neutropenic patients, and patients with febrile neutropenia should undergo treatment with antibiotics 3, 4.

Management of Neutropenia

• Management of severe chronic neutropenia includes commonsense precautions to avoid infection, aggressive treatment of bacterial or fungal infections, and administration of G-CSF 2, 5.
• Patients with severe chronic neutropenia are at risk of eventually developing myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) and require monitoring for this complication 5.
• Hematopoietic stem cell transplantation is a curative therapy for congenital neutropenia with MDS/AML or with cytogenetic abnormalities indicating impending conversion 5.

Prophylactic Antibiotics in Neutropenia

• Prophylactic antibiotics are associated with risks and have limited mortality benefit, but early antibiotic use in febrile neutropenia is critical 4.
• Ciprofloxacin with erythromycin is effective prophylaxis against Gram-negative bacteraemia in neutropenic patients, but does not prevent coagulase-negative staphylococcal bacteraemia and selects for resistant strains 6.