What do abnormal laboratory results indicate?

Understanding Abnormal Laboratory Results

The interpretation of abnormal laboratory results requires understanding the specific analyte that is abnormal, the clinical context, and recognition that the extent of abnormality is not necessarily a guide to clinical significance. 1

Principles of Laboratory Result Interpretation

General Approach

• Laboratory results must be interpreted within the clinical context of the individual patient
• The degree of abnormality does not always reflect clinical severity
• Reference ranges are typically defined as the mean ± 2 standard deviations in a presumably healthy population
• A normal value does not completely exclude the presence of disease

False Results Considerations

• False-negative results may occur due to:

  • Invalid sample submission
  • Timing of use relative to testing
  • Cutoff concentration set too high
  • Substance not included in standard test panel 2

• False-positive results may occur due to:

  • Cross-reactivity with unrelated substances (e.g., fluoroquinolone antibiotics can cross-react with opiate screens)
  • Legitimate prescription medications
  • Certain foods that metabolize into tested substances 2

Significance of Abnormal Results

Persistence of Abnormalities

• Transient abnormalities may resolve without intervention
• Persistent abnormalities (≥6 months) typically warrant additional evaluation
• When liver blood tests were repeated, 84% remained abnormal after 1 month and 75% remained abnormal after 2 years 2

Clinical Significance by Degree of Abnormality

1. Critical values: Require immediate intervention
2. Significant abnormalities: Require targeted treatment or further investigation
3. Borderline results: May require monitoring or repeat testing

Examples of Clinical Significance

• A patient with hepatitis A can have ALT values >1000 U/L but may recover completely without intervention
• A patient with hepatitis C can have ALT within normal reference range but is at substantial risk of progressing to end-stage liver disease if not diagnosed and treated 2

Diagnostic Approach for Specific Abnormalities

Liver Function Tests

• For mild elevations (liver enzymes <5× normal), evaluate with noninvasive serologic tests
• For marked elevations (>5× normal), consider viral hepatitis A, E, and cytomegalovirus
• In cases of cholestatic enzyme elevations with history of autoimmune or inflammatory bowel disease, consider primary sclerosing cholangitis 1

Diabetes Diagnosis

• Diagnosis requires two abnormal test results from the same sample or in two separate test samples
• If using two separate samples, the second test should be performed without delay
• If two different tests (such as A1C and FPG) are both above diagnostic threshold, this confirms diagnosis
• For discordant results from two different tests, repeat the test that is above the diagnostic cut point 2

Drug Testing

• Direct observation is the most reliable method for specimen collection
• Random specimens or those taken without supervision should be labeled as such
• Specimens with legal implications may require collection in a tamper-proof container with chain of custody 2

Special Considerations

Patient Populations

• In children, consider broader differential diagnosis and include anti-liver kidney microsomal antibodies and anti-celiac antibodies
• In patients with HIV treated with certain drugs or with iron-deficient anemia, A1C is less reliable than blood glucose measurement 2

Concomitant Conditions

• Consider the presence and magnitude of concomitant inflammatory response
• The incidence of abnormally elevated serum transaminases is greater in patients taking multiple medications, especially hepatotoxic ones 3

Action Plan for Abnormal Results

1. Immediate referral for:

   • Unexplained clinical jaundice
   • Suspicion of possible hepatic or biliary malignancy 2

2. Expedited evaluation for:

   • Markedly elevated abnormalities
   • Persistent abnormalities

3. Follow-up testing to:

   • Evaluate treatment effectiveness
   • Adjust treatment based on trend analysis rather than single values

Common Pitfalls to Avoid

• Repeating the same tests without investigating underlying cause
• Assuming degree of abnormality reflects clinical significance
• Failing to consider demographic factors (age, sex, ethnicity) that affect reference ranges
• Overlooking that current upper limits of normal may be too high due to inclusion of subclinical conditions in reference populations 1

Remember that abnormal laboratory results are tools for clinical decision-making, not diagnostic endpoints themselves. The specific analyte that is abnormal matters more than the degree of abnormality, and all results must be interpreted in the context of the individual patient's clinical presentation.