Interpreting Laboratory Results: Evidence-Based Approach
Laboratory test interpretation requires understanding the clinical context, timing of testing, potential interferences, and the specific limitations of each assay to avoid diagnostic errors that could harm patients.
General Principles for Result Interpretation
Context is Critical
- All laboratory results must be interpreted within the clinical context, including the patient's medications, timing relative to clinical events, and physiological state 1
- Results obtained during acute illness, pregnancy, or immediately post-thrombosis may not accurately reflect baseline status and should be repeated when the patient is stable 1
- The reference interval describes the population from which it was determined and reflects cultural, biological, physiological and behavioral diversity 2
Understanding Test Limitations
- Every test has inherent analytical imprecision (typically ≤10%), meaning results near cutoff values should be interpreted with caution 1
- False-positive results can occur due to cross-reactivity with other substances, while false-negative results may occur if the substance tested is not included in the panel or if timing is suboptimal 1, 3
- Screening tests (like immunoassays) have known specificity limitations and require confirmatory testing before making clinical decisions 3
Specific Interpretation Strategies
When Results Are Near Cutoff Values
- Small differences (≤10%) around cutoff values may influence classification as positive or negative due to assay imprecision 1
- Retesting is recommended to confirm equivocal results 1
- Results should be interpreted according to local cutoff values stated in the laboratory report 1
Timing Considerations
- Delay testing as long as possible after red blood cell transfusion (ideally 50+ days) to avoid false-negative results from donor cell contamination 1
- Testing during pregnancy may show fluctuating results, with some markers decreasing in the second and third trimesters 1
- Post-thrombotic testing should be performed at a distance from the acute event to avoid falsely low antibody titers 1
Medication Interferences
- Always obtain a complete medication history before interpreting results, as many prescribed medications can cause false-positive results 3
- Anticoagulant therapy (warfarin, DOACs, heparin) can significantly interfere with coagulation testing and requires special interpretation 1
- Some medications may cross-react with immunoassays (e.g., trazodone causing false-positive amphetamine screens, fluoroquinolones cross-reacting with opiate screens) 1, 3
Confirmatory Testing Requirements
When to Order Confirmatory Tests
- Always order confirmatory testing (such as GC-MS) before making clinical decisions based on positive screening immunoassays 3
- Confirmatory tests are highly specific and unlikely to yield false-positive results, though they may still show "clinical false-positives" when patients take certain prescribed medications 1
- For antiphospholipid antibodies, two consecutive positive tests at least 12 weeks apart are required to rule out transient positivity 1
Interpreting Discordant Results
- When test results conflict with clinical findings, seek assistance from the testing laboratory or a toxicologist 1, 3
- Results that don't correlate with the clinical picture should prompt consideration of analytical errors, specimen issues, or alternative diagnoses 1
- Discuss unexpected positive results promptly with the patient in a non-judgmental manner before taking action, keeping in mind the possibility of false-positive results 3
Documentation and Reporting
Essential Elements to Document
- Record the clinical context: timing relative to transfusions, medications, acute events, and pregnancy status 1
- Note any potential interferences (anticoagulant therapy, acute phase proteins) that may affect interpretation 1
- Include the date of testing, as newer testing methods may not have been available during previous evaluations 1
Result Reporting Standards
- Results should include detailed findings with a final conclusion (positive/negative) and warnings about potential interferences 1
- Quantitative results should be reported with their level relative to the cutoff value 1
- Close interaction between laboratory and clinician is essential for proper interpretation 1
Common Pitfalls to Avoid
Critical Errors in Interpretation
- Never make punitive decisions or discharge patients based solely on screening test results without confirmatory testing 3
- Do not assume all positive results represent the suspected condition—many prescribed medications and physiological states cause false positives 1, 3
- Avoid testing during suboptimal conditions (acute illness, recent transfusion, high-dose anticoagulation) when results may be unreliable 1
Recognizing False Results
- False-positive laboratory results are 8 times more frequent than true positives in routine testing populations 3
- Results obtained during pregnancy or the acute post-thrombotic phase should be repeated postdelivery or at a distance from the event 1
- Bad sample storage conditions can lead to false-positive results; concomitant testing of a normal control can help identify this issue 1
Risk Stratification Based on Results
High-Risk Profiles
- Triple-positive or double-positive results (with concordant isotype) increase confidence in diagnosis and indicate higher risk 1
- IgG isotype is regarded as clinically more relevant than IgM for most antibody testing 1
- Persistent medium/high titers (>99th percentile) are of utmost importance for diagnosis 1
Lower-Risk or Uncertain Profiles
- Single positive results, especially isolated IgM, are regarded as less clinically relevant 1
- Results that fluctuate over time or become negative on repeat testing suggest transient positivity not sufficient for diagnosis 1
- Low positive results around the cutoff value require careful interpretation and often repeat testing 1