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

From the Guidelines

Investigations for neutropenia should begin with a complete blood count with differential, peripheral blood smear, and bone marrow aspiration and biopsy to assess cellularity and maturation of neutrophil precursors, as recommended by recent guidelines 1. The initial evaluation should also include a thorough physical examination to identify potential sites of infection, such as the periodontium, pharynx, lower esophagus, lung, perineum, and skin, including bone marrow aspiration sites, vascular catheter access sites, and tissue around the nails 1. Additional blood tests should include:

• Vitamin B12 and folate levels
• Liver and renal function tests
• Inflammatory markers (ESR, CRP)
• Autoimmune markers like ANA and rheumatoid factor
• Specific antibody tests for infections such as HIV, hepatitis, CMV, and EBV, which can cause neutropenia Genetic testing may be warranted in suspected congenital neutropenias, including testing for ELANE, HAX1, or G6PC3 mutations 1. The investigation approach should be tailored based on the severity of neutropenia, associated symptoms, and clinical context, with urgent evaluation needed for febrile neutropenia, and consideration of risk-stratification according to susceptibility to infection, as recommended by the Infectious Diseases Society of America 1. In patients with neutropenic fever, empiric treatment with broad-spectrum antibiotics is strongly recommended, and assessments of cellular/humoral immunity, where available, should be performed 1.

From the Research

Investigations for Neutropenia

The following investigations are required for neutropenia:

• Complete blood count (CBC) with differentials to confirm the diagnosis of neutropenia 2, 3, 4, 5
• Bone marrow examination with cytogenetics to evaluate the production of neutrophils and rule out underlying hematologic disorders 3, 4, 5
• Neutrophil antibody testing to diagnose autoimmune neutropenia 3
• Genetic testing to diagnose congenital neutropenias 3, 4
• Screening for vitamin B12 and folate deficiencies, as well as other nutritional deficiencies such as iron and zinc 6, 5
• Testing for infections such as hepatitis B and C, cytomegalovirus, and human immunodeficiency virus 5
• Evaluation of liver and thyroid function 5
• Imaging studies such as chest roentgenogram and abdominal echography to rule out underlying diseases 5
• Direct and indirect antiglobulin test to diagnose autoimmune hemolytic anemia 5
• Assessment of serum proteins and rheumatoid factor to diagnose autoimmune diseases 5

Classification of Neutropenia

Neutropenia can be classified into:

• Acute neutropenia, which evolves over a few days and occurs when neutrophil use is rapid and production is impaired 4
• Chronic neutropenia, which lasts for 3 months or longer and is a result of reduced production, increased destruction, or excessive splenic sequestration of neutrophils 4
• Severe neutropenia, which is defined as an absolute neutrophil count below 500/μL and increases susceptibility to bacterial or fungal infections 2, 4

Causes of Neutropenia

The causes of neutropenia can be categorized into:

• Intrinsic defects arising from impaired proliferation and maturation of myeloid progenitor cells in the bone marrow 4
• Acquired disorders of myeloid progenitor cells 4
• Secondary causes extrinsic to bone marrow myeloid cells, such as medications, infections, and autoimmune diseases 3, 4, 5