What is the appropriate workup for a patient presenting with neutropenia?

Neutropenia Workup

The workup for neutropenia should begin with a complete blood count with differential to confirm the absolute neutrophil count (ANC), followed by a comprehensive metabolic panel, blood cultures (if febrile), and bone marrow examination for severe or unexplained cases. 1, 2

Initial Laboratory Assessment

• Obtain a CBC with differential to confirm neutropenia and assess severity: mild (ANC 1000-1500/mm³), moderate (ANC 500-1000/mm³), or severe (ANC <500/mm³) 1, 3
• Examine the peripheral blood smear to evaluate cell morphology and identify abnormal cells 2
• Measure serum creatinine, blood urea nitrogen, electrolytes, hepatic transaminases, and total bilirubin 4, 1
• Consider vitamin B12, folate, and copper levels if nutritional deficiency is suspected 3

History and Physical Examination Focus

• Medication history is critical as drug-induced neutropenia is a common cause; review all current and recent medications 1
• Assess for recent infections, particularly viral infections (HIV, hepatitis, EBV) which are strongly associated with neutropenia 1, 5
• Document history of recurrent infections, oral ulcers, skin infections, and periodontal disease which suggest chronic severe neutropenia 2
• Family history may reveal inherited neutropenia syndromes 2, 3
• Physical examination should focus on: periodontium, pharynx, skin for infections or lesions, perineum, and any indwelling catheter sites 4, 1, 6

Blood Cultures and Infectious Workup

• Obtain at least 2 sets of blood cultures if the patient is febrile or has signs of infection 4, 1
• If a central venous catheter is present, draw blood cultures from each lumen plus a peripheral vein site 4, 1
• Urinalysis and urine culture should be performed if urinary symptoms are present or if a urinary catheter is in place 1, 6
• Chest radiography is indicated only if respiratory signs or symptoms are present 1, 6

Risk Stratification for Febrile Neutropenia

If the patient presents with fever (single oral temperature ≥38.0°C or ≥37.5°C axillary), immediate risk stratification is essential 4, 6:

• High-risk criteria include: ANC <100 cells/mm³ anticipated to last >7 days, MASCC score <21, hemodynamic instability, severe mucositis, gastrointestinal symptoms, neurologic changes, catheter tunnel infection, pulmonary infiltrates, or hepatic/renal insufficiency 4
• Low-risk criteria include: MASCC score ≥21, anticipated brief neutropenia (<7 days), clinically stable, and few comorbidities 4

Bone Marrow Evaluation

• Bone marrow aspirate and/or biopsy with cytogenetic testing is essential for diagnostic evaluation in severe neutropenia (ANC <500/mm³), unexplained chronic neutropenia, or when hematologic malignancy is suspected 2, 3
• Bone marrow examination helps differentiate between decreased production (hypocellular marrow, maturation arrest) versus increased destruction or peripheral sequestration 2

Additional Testing Based on Clinical Context

• Antineutrophil antibodies if autoimmune neutropenia is suspected 3
• Genetic testing may be required for inherited neutropenia syndromes (cyclic neutropenia, severe congenital neutropenia, bone marrow failure syndromes) 3
• HIV testing should be strongly considered given the strong association between HIV and neutropenia 5
• Imaging beyond chest X-ray (including chest CT) should be performed based on clinical signs and symptoms suggesting specific sites of infection 4, 1

Critical Management Considerations

• Febrile neutropenia is an oncologic emergency requiring empiric broad-spectrum antibiotics within 2 hours of presentation 1, 7
• Severe neutropenia (ANC <500/mm³) carries significant infection risk, particularly from organisms resident on body surfaces 2
• Moderate-severe neutropenia is associated with dramatically increased risk of haematological malignancies (odds ratio 46.03) and mortality (>50% absolute risk), necessitating urgent follow-up 5

Common Pitfalls to Avoid

• Inadequate blood culture volumes reduce diagnostic yield; ensure proper collection technique 1
• Delaying antibiotic therapy in febrile neutropenic patients can lead to rapid clinical deterioration and sepsis 1
• Overlooking medication-induced neutropenia is common; systematically review all medications including over-the-counter drugs 1, 3
• Failing to recognize that signs of inflammation may be minimal or absent in neutropenic patients despite serious infection 4, 6