What blood tests are relevant for diagnosing prolonged fever?

Relevant Blood Tests for Prolonged Fever

For patients with prolonged fever (>10 days), a comprehensive diagnostic workup should include complete blood count with differential, inflammatory markers, liver function tests, urinalysis, and blood cultures as first-line laboratory investigations. 1, 2

Initial Laboratory Evaluation

Complete Blood Count (CBC) with Differential

• White blood cell (WBC) count may be normal in up to 75% of patients with prolonged fever, but is still essential for evaluation 1, 3
• Presence of leukocytosis (WBC ≥14,000/mm³) or left shift (≥16% bands or ≥1,500 band neutrophils/mm³) warrants careful assessment for bacterial infection 1
• Mild thrombocytopenia may be present in early illness (approximately one-third of patients), sometimes followed by thrombocytosis 1
• Neutrophil-to-lymphocyte ratio (NLR) may be more useful than absolute WBC count in diagnosing septic shock 4
• Anemia may be present and should be evaluated as it could indicate chronic disease or malignancy 5

Inflammatory Markers

• C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) should be measured in all patients with prolonged fever 1
• CRP ≥3.0 mg/dL and/or ESR ≥40 mm/hr are significant indicators of inflammation 1
• CRP may be a better indicator of infection than WBC count in some patients, particularly when WBC count is normal 3
• Procalcitonin levels can help discriminate bacterial infection from other inflammatory processes causing fever 1

Liver Function Tests

• Liver enzyme levels are commonly elevated in up to 85% of patients with certain infections like Q fever 1
• Hyperbilirubinemia occurs in approximately 25% of patients with certain infections 1
• Albumin levels <3.0 g/dL may indicate inflammation or chronic disease 1

Urinalysis and Urine Culture

• Urinalysis for leukocyte esterase and nitrite by dipstick, plus microscopic examination for WBCs 1
• Pyuria (≥10 WBCs/high-power field) or positive leukocyte esterase/nitrite test should prompt urine culture 1
• Should not be performed routinely in asymptomatic patients 1

Second-Line Laboratory Tests

Blood Cultures

• Should be obtained if bacteremia is suspected, especially in critically ill patients 1
• May have low yield in some settings but are essential if endocarditis or other serious infection is suspected 1

Serologic Testing

• For suspected infectious causes like Q fever, serologic testing for specific antibodies (IgG and IgM) should be performed 1
• Paired acute and convalescent samples (3-6 weeks apart) may be necessary to confirm diagnosis 1

Molecular Diagnostic Tests

• Polymerase chain reaction (PCR) testing of blood or other specimens for specific pathogens when indicated 1
• Endotoxin activity assay may be useful in detecting Gram-negative infections 1

Special Considerations for Specific Patient Populations

Elderly Patients

• Fever may be absent in up to 48% of elderly patients with bacterial infections 6
• The combination of fever, leukocytosis, and bandemia has high specificity for bacterial infection in elderly patients 6
• Normal WBC count does not rule out infection in this population 1, 6

Children

• Evaluation for Kawasaki disease should be considered in children with prolonged fever (≥5 days) and 2-3 compatible clinical criteria 1
• Laboratory findings suggestive of Kawasaki disease include anemia, elevated ALT, albumin <3.0 g/dL, WBC ≥15,000/mm³, and platelet count ≥450,000 after the 7th day of fever 1

Immunocompromised Patients

• More extensive workup may be required, including testing for opportunistic infections 1
• Consider evaluation for autoinflammatory syndromes if recurrent fever episodes occur 1

When Initial Tests Are Inconclusive

• If ESR or CRP levels remain elevated and diagnosis is unclear after initial evaluation, consider 18F fluorodeoxyglucose positron emission tomography scan with computed tomography 2
• Tissue biopsy (liver, lymph node, bone marrow) may be necessary if noninvasive tests are unrevealing 2
• Consider consultation with infectious disease specialists for persistent unexplained fever 1, 2

Common Pitfalls to Avoid

• Relying solely on WBC count to rule out infection (normal WBC counts occur in many infections) 1, 3
• Failing to repeat laboratory tests if fever persists despite negative initial results 1
• Overlooking non-infectious causes of prolonged fever such as malignancy, autoimmune disorders, and drug reactions 2
• Starting empiric antimicrobial therapy without adequate diagnostic workup (not recommended except in neutropenic, immunocompromised, or critically ill patients) 2