What laboratory tests indicate neutropenia (low neutrophil count) in a patient?

Laboratory Tests Indicating Neutropenia

Neutropenia is diagnosed by obtaining a complete blood count (CBC) with differential, which measures the absolute neutrophil count (ANC), with neutropenia defined as an ANC <1,500 cells/mm³ in most populations, though clinically significant neutropenia requiring intervention is typically ANC <500 cells/mm³. 1

Primary Diagnostic Test

• CBC with differential leukocyte count and platelet count is the essential laboratory test to diagnose neutropenia 1
• The ANC is calculated from the CBC differential and represents the total number of mature neutrophils and band forms in circulation 1
• A peripheral blood smear should be examined to assess neutrophil morphology and identify any abnormal cells 2, 3

Severity Classification Based on ANC

The severity of neutropenia directly correlates with infection risk and guides clinical management:

• Mild neutropenia: ANC ≥1,000 to <1,500 cells/mm³ 2
• Moderate neutropenia: ANC ≥500 to <1,000 cells/mm³ 1, 2
• Severe neutropenia: ANC <500 cells/mm³ 1
• Profound neutropenia: ANC <100 cells/mm³ (highest infection risk) 1
• Agranulocytosis: ANC <200 cells/mm³ 2

Additional Laboratory Evaluation

When neutropenia is confirmed, additional tests help determine etiology and guide management:

• Serum creatinine and blood urea nitrogen to assess renal function and guide antibiotic dosing 1
• Electrolytes, hepatic transaminase enzymes, and total bilirubin to evaluate organ function and potential drug toxicity 1
• Blood cultures (at least 2 sets) are critical if fever is present, obtained from peripheral sites and each lumen of any central venous catheter 1
• Bone marrow aspirate and/or biopsy with cytogenetics for evaluation of chronic or unexplained neutropenia to assess production defects 4, 3

Clinical Context Matters

The duration of neutropenia is as important as the absolute count. Prolonged neutropenia (>7 days) with ANC <100 cells/mm³ defines high-risk patients who require hospitalization and IV antibiotics 1. Brief neutropenia (<7 days) with few comorbidities defines low-risk patients who may be managed as outpatients 1.

Common Pitfalls to Avoid

• Do not rely on relative neutrophil percentages alone—the absolute neutrophil count determines clinical significance and intervention urgency 5
• Repeat the CBC if neutropenia is discovered incidentally in an afebrile patient, as transient neutropenia from viral infections or medications is common 2, 6
• Do not delay blood cultures in febrile neutropenic patients while waiting for other test results, as bacteremia occurs in >10-20% of patients with ANC <100 cells/mm³ 1
• Recognize that signs of infection are often absent in severe neutropenia—fever may be the only indicator, and typical inflammatory signs (erythema, induration, pustulation) are diminished or absent 1

Risk Stratification Tools

The MASCC (Multinational Association for Supportive Care in Cancer) score can formally differentiate high-risk (score <21) from low-risk (score ≥21) patients with febrile neutropenia, though this applies specifically to cancer patients 1. High-risk features include profound neutropenia (ANC <100 cells/mm³), anticipated prolonged duration (>7 days), hemodynamic instability, mucositis, or significant comorbidities 1.