What initial investigations to order and how to interpret results?

Initial Investigations for Patient Workup

The most important initial investigations for any patient workup should include a comprehensive metabolic panel, complete blood count, thyroid function tests, and vitamin B12 levels, as these can identify the most common causes of generalized symptoms and provide critical baseline information for further diagnostic decision-making. 1

Core Laboratory Tests

First-line Investigations

• Complete Blood Count (CBC) - Evaluates for anemia, infection, inflammation, and hematologic malignancies
• Comprehensive Metabolic Panel (CMP) - Assesses:
  • Electrolytes (sodium, potassium, chloride, bicarbonate)
  • Kidney function (BUN, creatinine)
  • Liver function (AST, ALT, bilirubin, albumin)
  • Glucose levels
• Thyroid Function Tests (TSH, free T4) - Essential to evaluate for hypo/hyperthyroidism 1
• Vitamin B12 Level - Critical as deficiency can present with neurological symptoms before anemia develops 1

Second-line Investigations

• Inflammatory markers (ESR, CRP) - To identify autoimmune or inflammatory conditions 1
• Iron studies (ferritin, iron, TIBC, transferrin saturation) - Particularly important in women of reproductive age 1
• Creatine kinase (CK) - To assess for possible myopathy or muscular disorders 1
• Lipid profile - For cardiovascular risk assessment 1

Disease-Specific Investigations

For Suspected Liver Disease

• Liver blood tests - ALT, AST, ALP, GGT, bilirubin
• Note: The extent of liver blood test abnormality is not necessarily a guide to clinical significance; even mild abnormalities can indicate significant underlying disease 2
• Caution: Many patients with significant liver fibrosis may have liver enzymes within normal reference ranges 2

For Suspected Hematologic Malignancy

• Peripheral blood smear
• Bone marrow aspiration and biopsy if indicated by CBC abnormalities
• Flow cytometry for suspected leukemia 2

For Suspected Autoimmune Encephalitis

• Brain MRI with contrast - Can show changes consistent with limbic encephalitis or other patterns 2
• Cerebrospinal fluid analysis - To rule out infectious causes and evaluate for inflammatory markers 2

Interpretation Principles

1. History remains paramount - Research shows that in 76% of cases, the history leads to the final diagnosis, while physical examination (12%) and laboratory investigations (11%) confirm or refine it 3

2. Abnormal results are common - Even when pretest probability is low, up to 57.7% of patients will have at least one abnormal test result, with 12.4% having markedly abnormal values 4

3. Consider clinical context - The significance of abnormal results depends on the specific analyte and clinical context, not just the degree of abnormality 2

4. Avoid unnecessary repeat testing - Simply repeating abnormal tests without investigating etiology is only justified when there's high certainty the abnormality will resolve 2

5. Order tests with purpose - An estimated $6.8 billion of medical care in the US involves unnecessary testing that doesn't improve patient outcomes 5

Red Flags Requiring Urgent Evaluation

• Loss of motor milestones or regression of skills
• Respiratory symptoms with generalized weakness
• Rapidly progressive weakness (possible Guillain-Barré syndrome)
• Clinical jaundice or suspicion of hepatic/biliary malignancy 2, 1

Common Pitfalls to Avoid

1. Relying solely on laboratory values, especially in early presentations of severe pathologies 1

2. Assuming mild abnormalities are clinically insignificant - Chronic conditions like NAFLD, alcohol-related liver disease, and hepatitis C often present with only mild or moderate liver blood test abnormalities 2

3. Delaying imaging studies in hemodynamically unstable patients 1

4. Omitting blood cultures before starting antibiotics in suspected sepsis 1

5. Information order bias - The order in which clinical information is presented can influence diagnostic probability estimates; be aware of this cognitive bias 6

By following this structured approach to initial investigations, clinicians can efficiently identify the underlying cause of a patient's presentation while avoiding unnecessary testing and potential diagnostic delays.