What are the investigations for neutropenia (low neutrophil count)?

From the Guidelines

The investigation for neutropenia should begin with a complete blood count with differential to confirm the neutropenia and assess other cell lines, followed by a thorough history and physical examination to identify signs of infection, lymphadenopathy, hepatosplenomegaly, and other systemic findings. Initial workup should include laboratory tests such as peripheral blood smear, reticulocyte count, liver and kidney function tests, vitamin B12 and folate levels, and inflammatory markers like ESR and CRP 1.

Key Components of the Investigation

• A thorough history focusing on medication use, recent infections, family history, and symptoms of underlying diseases
• Physical examination to look for signs of infection, lymphadenopathy, hepatosplenomegaly, and other systemic findings
• Laboratory tests to include peripheral blood smear, reticulocyte count, liver and kidney function tests, vitamin B12 and folate levels, and inflammatory markers like ESR and CRP
• Bone marrow examination is indicated for severe, persistent, or unexplained neutropenia to rule out primary bone marrow disorders
• Additional testing may include autoimmune markers (ANA, rheumatoid factor), HIV testing, and specific genetic testing if congenital neutropenia is suspected
• Imaging studies like chest X-ray or abdominal ultrasound may be warranted based on clinical findings

Risk Stratification

The investigation should also include risk stratification of patients with fever and neutropenia according to susceptibility to infection, with high-risk patients being 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, and low-risk patients being those with anticipated brief (<7 days) periods of neutropenia and few comorbidities or with a MASCC score of ≥21 1.

Severity Assessment

Severity assessment is crucial, as patients with absolute neutrophil counts below 500/μL are at high risk for serious infections and may require prophylactic antibiotics or granulocyte colony-stimulating factors depending on the underlying cause and clinical presentation 1.

Treatment Approach

The investigation aims to differentiate between acquired causes (medications, infections, autoimmune disorders) and congenital causes, as treatment approaches differ significantly 1.

From the Research

Investigation for Neutropenia

• Neutropenia is defined as the reduction in the absolute number of neutrophils in the blood circulation 2.
• The etiology of neutropenia may vary from transient bone marrow suppression to previously undiagnosed congenital syndromes or serious systemic diseases 3.
• Laboratory evaluation generally includes repeat complete blood cell counts (CBCs) with differentials and bone marrow examination with cytogenetics 4.
• Neutrophil antibody testing may be useful but only in the context of clinical and bone marrow findings 4.
• A structured approach to the evaluation of individuals with incidental neutropenia may make the identification of clinically silent diseases possible, and provide an opportunity for early treatment, avoiding complications of the diseases and consequences of neutropenia 5.

Diagnostic Approach

• The diagnosis and management of neutropenia can be challenging, and a stepwise approach is recommended, focusing first on reaching a provisional diagnosis and treatment plan, then steps to a final diagnosis 6.
• Experts agree that patients with acute febrile neutropenia should be treated with antibiotics and that patients at high risk of severe neutropenia (>20% risk) after myelosuppressive chemotherapy should be treated prophylactically with a myeloid growth factor, usually G-CSF 6.
• The discovery of genes responsible for congenital neutropenias now permits genetic diagnosis in many cases 4.
• Chronic idiopathic neutropenia of adults was identified in 34.0% of the individuals, neutropenia due to exposure to chemical agents was seen in 16.5%, infectious diseases in 9.3%, autoimmune diseases in 9.3%, haematological diseases in 9.3%, thyroid disorders in 8.2%, ethnic neutropenia in 7.2%, drug-related neutropenia in 2.1%, cyclic neutropenia in 2.1% and iron deficiency in 2.1% 5.

Management

• 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.
• 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 4.
• Hematopoietic stem cell transplantation is a curative therapy for congenital neutropenia with MDS/AML or with cytogenetic abnormalities indicating impending conversion 4.