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Laboratory Test Interpretation: A Practical Framework

Laboratory test results must always be interpreted in the context of the patient's clinical presentation, timing of sample collection, medication history, and the specific assay methodology used—never in isolation. 1, 2

Understanding Reference Ranges and Their Limitations

Reference intervals describe the central 95% of values from healthy populations, meaning 5% of healthy individuals will have "abnormal" results by definition. 3, 4 This fundamental statistical reality explains why many flagged results lack clinical significance.

Key Factors Affecting Laboratory Values

• Biological variation within individuals is often more significant than laboratory error when repeat testing shows different results 5
• Age-related changes can alter alkaline phosphatase, fasting glucose, ESR, hemoglobin, and creatinine clearance without representing pathology, particularly in patients over 75 years 5
• Race and ethnicity significantly impact normal ranges—for example, serum creatinine reference ranges differ between White females (0.50-1.10 mg/dL) and Asian females (0.43-0.88 mg/dL) 1
• Gender differences affect ALT (upper limits 35-79 U/L for men vs 31-55 U/L for women), total bilirubin, cholesterol, and calcium 1

Critical Pre-Analytical Factors to Consider

Timing and Sample Collection Issues

• Fasting status affects tests containing hyaluronic acid and should be maintained for at least 2 hours before elastography 1
• Recent transfusions cause false-negative enzyme deficiency results—wait at least 50 days post-transfusion when possible, though 6-12% donor RBC contamination may persist 1
• Plasma exchange or IVIG can cause both false-negative and false-positive antibody results; retest 1-3 months after plasma exchange 1
• Disease activity affects antibody concentrations—MOG-IgG levels are higher during acute attacks than remission 1

Medication Interferences

• Anticoagulation therapy complicates lupus anticoagulant testing—DOAC removal procedures or alternative tests (TSVT/ET) may be needed during therapy 1
• Immunosuppression lowers antibody titers, potentially causing false-negative results 1
• Statins should be continued unless transaminases exceed 3× upper limit of normal (approximately 120-150 U/L) 2, 6

Interpreting Specific Test Categories

Autoantibody Testing

Weak positive results near cutoff values require confirmation with repeat testing after 12 weeks, as assay imprecision can reach 10% and transient positivity occurs. 1, 7

• MOG-IgG testing requires serum (not CSF), cell-based assays with Fc-specific secondary antibodies, and interpretation considering treatment status and disease phase 1
• Antiphospholipid antibodies need concurrent testing for lupus anticoagulant, anticardiolipin IgG/IgM, and anti-β2GPI IgG/IgM, with two positive tests at least 12 weeks apart 1
• Triple or double positivity (with concordant isotype) increases diagnostic confidence; single IgM positivity is less clinically relevant 1

Liver Function Tests

Review all previous LFT results first to distinguish acute elevation from chronic abnormality, as this fundamentally changes management. 2, 6

• Check INR and bilirubin immediately—coagulopathy or hyperbilirubinemia constitutes a medical emergency requiring ICU admission 2
• Magnitude of elevation does not correlate with prognosis—diagnosis and context matter more than absolute values 2
• Confirm hepatic origin of elevated alkaline phosphatase by checking GGT 6
• Measure creatine kinase to exclude muscle injury as cause of elevated AST 6

Enzyme Deficiency Testing

PK activity should be expressed as percentage of normal activity at 37°C, with results interpreted cautiously if obtained within 50 days of transfusion. 1

• False-negative results occur from reticulocytosis (which have 4× higher PK activity), recent transfusions, or inadequate sample storage 1
• Activity below 81.5% of normal distinguishes PK deficiency from other hemolytic conditions with 96.9% specificity 1

Common Pitfalls to Avoid

• Do not assume laboratory error when confronted with unexpected results—intraindividual biological variation is far more common 5
• Do not initiate treatment based solely on weak positive autoantibody results without clinical correlation and confirmatory testing 7
• Do not discontinue statins reflexively for mild LFT elevations, as this denies proven cardiovascular mortality benefit 2
• Do not overlook acetaminophen toxicity in patients with very high transaminases (>3,500 IU/L) even without clear ingestion history 2
• Do not use population reference intervals as clinical decision limits—they describe healthy populations, not disease thresholds 4

Algorithmic Approach to Abnormal Results

1. Verify the result is truly abnormal by reviewing previous values and considering patient-specific factors (age, race, gender) 1, 3
2. Assess pre-analytical variables: fasting status, medications, recent transfusions, sample timing relative to disease activity 1
3. Determine clinical urgency: Check for acute liver failure markers, coagulopathy, or other emergent conditions 2, 6
4. Confirm with repeat testing when results are borderline or unexpected, ideally using a methodologically different assay 1, 7
5. Interpret in clinical context: Laboratory values alone never establish or exclude diagnosis without supporting clinical features 1, 8

Documentation Requirements

Laboratory reports must include immunoglobulin class detected, assay type, antigenic substrate, biomaterial used, titer/concentration/units, assay-specific cutoffs, and performing laboratory. 1 This transparency allows proper interpretation and comparison across testing episodes.