What bloodwork is needed for a definitive diagnosis of lupus in a young to middle-aged woman, especially those from high-risk ethnic groups?

Bloodwork for Definitive Diagnosis of Lupus

For a definitive diagnosis of systemic lupus erythematosus (SLE), begin with antinuclear antibody (ANA) testing as the primary screening test, followed by a confirmatory panel including anti-dsDNA and anti-Sm antibodies, complement levels (C3, C4), complete blood count, and antiphospholipid antibodies including lupus anticoagulant testing. 1, 2

Sequential Testing Algorithm

Initial Screening Test

• ANA testing is the mandatory first step with nearly 100% sensitivity for SLE, making it the best screening assay to rule out the disease 2, 3
• An ANA titer of 1:40 or greater with characteristic multiorgan involvement supports the diagnosis 4
• ANA should only be ordered in patients with unexplained involvement of two or more organ systems to avoid false-positive results in low-prevalence populations 4

Confirmatory Autoantibody Panel (if ANA positive)

The following specific antibodies should be tested to confirm SLE diagnosis:

• Anti-dsDNA antibodies: Highly specific for SLE (present in 40-80% of patients), correlates with disease activity and particularly active renal disease 2, 5
• Anti-Sm antibodies: Highly specific for SLE with strong confirmatory power even in patients unlikely to have the disease 1, 2, 3
• Anti-Ro/SSA and anti-La/SSB antibodies: Essential for prognostic information and must be checked before pregnancy due to neonatal lupus risk 2, 5
• Anti-RNP antibodies: Provide additional prognostic information 2

Antiphospholipid Antibody Testing

Lupus anticoagulant (LA) testing is critical and must include: 1, 2

• Two tests based on different principles: dilute Russell's viper venom time (dRVVT) as the first test, and sensitive aPTT (with low phospholipids and silica as activator) as the second test 6
• Critical timing: Blood must be collected before starting any anticoagulant therapy or after sufficient discontinuation period 6, 2
• Proper specimen handling: Fresh venous blood in 0.109 M sodium citrate with double centrifugation to ensure platelet-poor plasma 6, 2
• Confirmation requirement: Positive LA results must be repeated >12 weeks later to confirm persistence 6, 2

Complement Levels

• C3 and C4 levels are essential at baseline as low complement predicts flares and correlates with active disease, especially renal involvement 2
• These should be monitored regularly throughout the disease course 1, 2

Routine Laboratory Tests

• Complete blood count (CBC): To detect cytopenias; severe anemia, thrombocytopenia, and leukopenia correlate with organ involvement and worse prognosis 2
• Urinalysis with urine protein/creatinine ratio: Essential for detecting and monitoring lupus nephritis 2
• Serum creatinine and albumin: Provide prognostic information about renal involvement 2
• ESR and CRP: For baseline and monitoring; significantly elevated CRP suggests superimposed infection 2

Common Pitfalls to Avoid

Lupus Anticoagulant Testing Errors

• Do not test patients already on anticoagulation as this interferes with the assay; wait for sufficient discontinuation period 6
• Ensure proper specimen processing with double centrifugation to achieve platelet-poor plasma (<10^7/mL platelets), as residual platelets cause false-negative results 6
• Avoid single-test screening: At least two different tests (dRVVT and sensitive aPTT) are required to rule out LA 6, 7
• Do not diagnose on single positive result: Confirmation testing at >12 weeks is mandatory 6, 2

ANA Testing Pitfalls

• Low predictive value in asymptomatic patients: Only order ANA when clinical suspicion exists with multiorgan involvement 4
• ANA-negative SLE exists: Patients with persistent characteristic multisystem involvement may have disease despite ANA <1:40 4

Interpretation Considerations

• Anti-Sm antibodies are highly specific but only present in a subset of SLE patients, so their absence does not rule out disease 2, 5
• Approximately 60% of patients with LA will also have anticardiolipin antibodies, but both should be tested as they can occur independently 7