What lab workup is recommended for a patient with unknown symptoms?

Lab Workup for Patients with Unknown Symptoms

The appropriate laboratory workup depends entirely on the clinical presentation and suspected diagnosis, but a foundational panel should include complete blood count (CBC) with differential, comprehensive metabolic panel (electrolytes, renal and hepatic function), inflammatory markers (ESR, CRP), and additional targeted tests based on specific clinical findings.

General Approach to Lab Testing

The lab workup must be guided by the clinical context rather than ordered indiscriminately. However, certain baseline tests provide essential information across multiple diagnostic possibilities:

Core Laboratory Panel

For most patients presenting with undifferentiated symptoms, obtain:

• Complete blood count (CBC) with differential - evaluates for infection, anemia, and hematologic abnormalities 1
• Comprehensive metabolic panel including:
  • Serum electrolytes (sodium, potassium, calcium, magnesium, phosphate) 1
  • Renal function (creatinine, BUN) 1
  • Hepatic function (AST, ALT, alkaline phosphatase, bilirubin, albumin) 1
  • Glucose 1
• Inflammatory markers:
  • Erythrocyte sedimentation rate (ESR) 1
  • C-reactive protein (CRP) 1

Context-Specific Testing

The following tests should be added based on clinical suspicion:

For Cognitive or Behavioral Symptoms

The Alzheimer's Association recommends a multi-tiered approach 1:

• Tier 1 tests (obtain in all patients):
  • CBC with differential 1
  • Complete metabolic panel (Chem-20) with electrolytes, glucose, calcium, magnesium, phosphate 1
  • Thyroid-stimulating hormone (TSH) 1
  • Vitamin B12 level 1
  • Homocysteine level 1
  • CRP and ESR 1

For Suspected Lymphoma

When Hodgkin lymphoma is considered 1:

• CBC with differential and platelets 1
• ESR 1
• Serum lactate dehydrogenase (LDH) 1
• Albumin 1
• Liver and renal function tests 1
• HIV and hepatitis B/C testing (before anthracycline therapy) 1

For Suspected Infection or Sepsis

When systemic infection is suspected 1:

• CBC 1
• Serum creatinine and electrolytes 1
• Inflammatory markers (CRP, procalcitonin) 1
• Blood gas analysis 1
• Lactate 1
• Coagulation assessment 1
• Blood cultures (if febrile or septic)

For Suspected Inflammatory/Rheumatologic Conditions

When immune-mediated disease is considered 1:

• Creatine kinase (CK) 1
• Transaminases (AST, ALT) 1
• LDH and aldolase 1
• ESR and CRP 1
• Troponin (if cardiac involvement suspected) 1

Important Caveats

Avoid common pitfalls:

• ESR has limitations: It is affected by age, sex, renal disease, and has slower response time than CRP 2, 3. CRP is more sensitive and responds more quickly to clinical changes 2, 3.
• Context matters: An isolated abnormal lab value must be interpreted with the complete clinical picture, not in isolation 1.
• Timing considerations: For acute conditions requiring urgent intervention (e.g., Fournier's gangrene), laboratory testing should not delay definitive treatment 1.
• False positives/negatives: ESR has more false positive and false negative results compared to CRP 3.

When to Expand Testing

Consider additional specialized testing when:

• Initial workup is unrevealing but clinical suspicion remains high 1
• Patient has extreme age, education level, or complex demographic factors 1
• Specific organ system involvement is identified on initial evaluation
• Risk factors for specific conditions are present (e.g., diabetes screening with HbA1c and urine ketones in suspected Fournier's gangrene) 1

The key principle is that laboratory testing should be hypothesis-driven based on clinical presentation, not a "shotgun" approach, while ensuring core metabolic and hematologic parameters are assessed in nearly all patients.