What labs should be ordered for a patient diagnosed with antiphospholipid antibody syndrome?

Laboratory Testing for Antiphospholipid Antibody Syndrome (APS)

For patients diagnosed with antiphospholipid antibody syndrome, regular monitoring should include lupus anticoagulant (LA), anticardiolipin antibodies (aCL) IgG/IgM, and anti-beta2 glycoprotein I antibodies (aβ2GPI) IgG/IgM. 1

Core Laboratory Tests

• Lupus Anticoagulant (LA) testing using a 3-step methodology:

  • Screening tests
  • Mixing studies
  • Confirmatory tests
  • Results should be reported as positive or negative with warnings about potential interferences 1

• Anticardiolipin antibodies (aCL):

  • IgG and IgM isotypes
  • Measured by solid phase assays (ELISA or other validated systems)
  • Results reported with their level; positivity defined as values above the 99th percentile of normal controls 1, 2

• Anti-beta2 glycoprotein I antibodies (aβ2GPI):

  • IgG and IgM isotypes
  • Measured by solid phase assays
  • Results reported with their level; positivity defined as values above the 99th percentile of normal controls 1, 2

Testing Frequency and Follow-up

• Initial diagnosis confirmation: Two consecutive positive tests at least 12 weeks apart are required to rule out transient positivity 2, 1

• Routine monitoring: The optimal frequency for retesting persistently positive patients is still under investigation, but annual testing of LA, aCL, and aβ2GPI is commonly practiced to evaluate:

  • Fluctuation of titers
  • Changes in antibody profile over time
  • Potential therapeutic consequences 2

Special Testing Considerations

• LA testing during anticoagulation:

  • For patients on direct oral anticoagulants (DOACs): Use pretest DOAC removal procedures
  • For patients on vitamin K antagonists (VKAs): Consider Taipan snake venom time/ecarin time (TSVT/ET)
  • Ideally, assess LA 1-2 weeks after discontinuation of VKA (with or without bridging to LMWH) 1

• LA methodology requirements:

  • Parallel testing with both activated partial thromboplastin time (APTT) and dilute Russell's viper venom time (dRVVT)
  • Omitting either test increases risk of underdiagnosis in up to 55% of triple aPL-positive samples 1

Risk Stratification Considerations

• Antibody profile assessment:
  • Triple positivity (LA, aCL, and aβ2GPI) carries the highest thrombotic risk
  • Double positivity (aCL and aβ2GPI with concordant isotype) significantly increases confidence in APS diagnosis
  • IgG isotype antibodies are considered clinically more relevant than IgM 1, 2
  • Medium/high titer antibodies (>99th percentile) are of utmost importance for diagnosis 1

Emerging Tests (Not Yet Routine)

• Anti-domain I beta2-glycoprotein (aDI) antibodies:

  • May be useful in risk stratification but not currently included in diagnostic criteria
  • Not recommended for routine testing as they have no proven added value in diagnosis 3

• Antiphosphatidylserine-prothrombin (aPS/PT) antibodies:

  • May be considered in patients negative for LA, aCL, and aβ2GPI where there is suspicion of APS
  • Further research needed on their role in thrombotic and obstetric APS 2

• Thrombin generation (TG) assays:

  • Systematic reviews show increased activated protein C resistance in APS patients
  • Further research needed to identify potential added value in diagnosis 2

Common Pitfalls to Avoid

• Interpretation errors: Laboratory results must be interpreted in clinical context with knowledge of anticoagulation status 1

• Anticoagulation interference: LA testing can be affected by anticoagulant therapy, acute phase proteins, and other interferences 1, 4

• Low positive results: Values around the cutoff should be interpreted with caution due to potential 10% imprecision of solid phase methods 1

• Single positive IgM: Considered less clinically relevant than IgG positivity 1, 2