What is the workup for Antiphospholipid (APLA) syndrome?

From the Guidelines

The workup for antiphospholipid syndrome (APS) should include concurrent testing for lupus anticoagulant (LA), anticardiolipin (aCL) IgG and IgM, and anti-beta2 glycoprotein I (aβ2GPI) IgG and IgM, with measurement of LA in citrated plasma according to the ISTH-SSC recommendations 1. The initial evaluation involves screening for these antibodies, with a focus on LA, aCL, and aβ2GPI, as they are the cornerstone of laboratory criteria for APS diagnosis 1.

• Key tests include:
  • Lupus anticoagulant (LA) in citrated plasma, using a 3-step methodology (screening, mixing, and confirmation) with parallel testing in APTT and dRVVT as first-choice clotting tests 1
  • Anticardiolipin (aCL) IgG and IgM, and anti-beta2 glycoprotein I (aβ2GPI) IgG and IgM, measured in plasma or serum by solid phase assays (ELISA or non-ELISA systems) 1
• Interpretation of results should be according to local cutoff values, with LA reported as positive or negative, and warning for potential interferences (anti-coagulant therapy, acute phase proteins) 1
• APL testing should be performed on two or more occasions at least 12 weeks apart to confirm persistent positivity, which is essential for APS diagnosis 1
• The aPL profile, including triple and double positivity, should be assessed to increase confidence in APS diagnosis, with IgG isotype regarded as clinically more relevant than IgM 1

From the Research

Antiphospholipid Syndrome (APS) Workup

The workup for Antiphospholipid Syndrome (APS) involves a combination of clinical and laboratory criteria. The diagnosis of APS requires the presence of a clinical criterion (thrombosis and/or pregnancy morbidity), combined with persistently circulating antiphospholipid antibodies (aPL) 2.

Laboratory Criteria

The laboratory criteria for APS include:

• Lupus anticoagulant (LAC)
• Anticardiolipin antibodies (aCL) IgG/IgM
• Anti-β2 glycoprotein I antibodies (aβ2GPI) IgG/IgM 2, 3 These antibodies should be demonstrable on at least 2 occasions separated by 12 weeks 4.

Challenges in Laboratory Testing

There are several challenges in laboratory testing for APS, including:

• LAC detection is prone to interference by anticoagulation therapy 2, 3
• Solid-phase assays for aCL and aβ2GPI exhibit discrepancies between different assays 2, 3
• Lack of universal calibrators or standards results in high variability between different solid-phase assays 2

Clinical Significance

The clinical significance of APS includes:

• Recurrent thrombosis (arterial, venous, microvascular) and/or pregnancy complications 5, 6
• Association with other autoimmune diseases, such as systemic lupus erythematosus 5, 6
• Treatment with antithrombotic therapy, which is the mainstay of treatment 6