General Principles for Interpreting Laboratory Results
Laboratory test results must always be interpreted within the complete clinical context of the patient's presentation, medication history, and overall clinical picture—never in isolation. 1
Essential Steps Before Interpretation
Obtain Complete Clinical Information
- Document all medications including prescription drugs, over-the-counter medications, and supplements before interpreting any test result 2, 3
- Review the patient's complete medical history, as many conditions and medications can affect test results 1
- Understand the specific clinical question being asked and whether the test result will actually impact management decisions 3
Verify Test Quality and Methodology
- Check specimen validity: Confirm proper collection, handling, and storage conditions 1
- Verify the assay method used, as different methodologies have different sensitivities, specificities, and potential interferences 1
- Review the laboratory's specific cutoff values and reference ranges, which are assay-dependent 1
- Ensure results are reported with appropriate units, methodology, and performing laboratory documentation 1
Understanding Test Limitations
Recognize Analytical Variability
- Small changes in quantitative results (e.g., ±0.3% for HbA1c) may reflect assay variability rather than true clinical change 1
- Screening immunoassays are presumptive only and have inherent limitations in specificity due to cross-reactivity with structurally similar compounds 2, 3, 4
- Results outside expected ranges or below reference intervals should be verified by repeat testing, ideally using a different analytical method 1
Account for Timing Issues
- Test results depend on disease activity, with concentrations varying during acute episodes versus remission 1
- Treatment status affects results, with lower concentrations during immunosuppression or after plasma exchange 1
- Detection windows vary by substance and testing matrix, potentially missing recent or remote exposures 1, 2
Interpreting Positive Results
Confirm Unexpected Positives
- Always review positive results with the patient first to determine whether something other than the suspected condition may explain the results 1
- Consider false-positives due to cross-reactivity, medication interference, or laboratory error 1, 2, 3
- Request confirmatory testing using gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS) when results are unexpected or will impact patient management 2, 3, 4
- Use a second methodologically different assay if discrepancies exist to reduce false-positive reproduction 1
Assess Clinical Significance
- Interpret results according to local cutoff values and clinical context, not just whether the result is "positive" or "negative" 1
- For antibody testing, repeat positive tests at least 12 weeks apart to rule out transient positivity that is insufficient for diagnosis 1
- Consider the positive predictive value, which varies with disease prevalence in the tested population 5
Interpreting Negative Results
Don't Dismiss Clinical Suspicion
- A negative test does not exclude the possibility of disease, especially if clinical suspicion remains high 1
- Consider retesting during acute episodes, treatment-free intervals, or after appropriate washout periods if initial testing is negative but suspicion persists 1
- Recognize that standard panels may not detect all relevant substances or variants 1, 2
Evaluate for Technical Issues
- Assess whether the specimen could have been diluted, substituted, or adulterated 1
- Consider whether the substance used is included in the test panel 1, 2
- Verify that timing of specimen collection was appropriate for the detection window 1, 2
Critical Pitfalls to Avoid
Never Make Consequential Decisions Without Confirmation
- Do not discharge patients from care, make custody decisions, or take legal actions based solely on screening test results without confirmatory testing 2, 3, 4
- Avoid assuming all positive screening results represent the suspected condition without considering alternative explanations 1, 2, 3
- Never dismiss ongoing symptoms just because a test result is negative 1
Maintain Appropriate Clinical Relationships
- Establish a working relationship with laboratory personnel or toxicologists for consultation on complex or unexpected results 2, 3, 4
- Seek expert advice from specialized centers when results conflict with clinical presentation 1
- Ensure close interaction between laboratory and clinician for proper interpretation 1
Understand Specific Test Characteristics
- Know which medications and conditions can interfere with specific assays 1, 2
- Recognize that different immunoglobulin classes (IgG, IgM, IgA) have different clinical relevance, with IgG generally more clinically significant 1
- Be aware that some tests (like certain antibody assays) may be affected by recent treatments such as IVIG or plasma exchange 1
Documentation and Reporting
Essential Elements to Document
- Immunoglobulin class detected, assay type, antigenic substrate, and biomaterial used 1
- Titer/concentration/units with assay-specific cutoffs 1
- Performing laboratory and methodology 1
- Any potential interferences such as anticoagulant therapy or acute phase proteins 1