From the Guidelines
The appropriate workup for Antiphospholipid Antibody (APA) Syndrome should include concurrent testing for lupus anticoagulant (LA), anticardiolipin antibodies (aCL) IgG and IgM, and anti-β2 glycoprotein I antibodies (aβ2GPI) IgG and IgM, with confirmation of positive results through repeat testing at least 12 weeks later, as recommended by the most recent guidelines 1.
Key Components of APA Syndrome Workup
- Lupus anticoagulant testing should be performed according to the ISTH-SSC recommendations, using a 3-step methodology with parallel testing in APTT and dRVVT as first-choice clotting tests 1.
- Measurement of aCL and aβ2GPI should be done in plasma or serum by solid phase assays, with results interpreted according to local cutoff values and reported with their level, considering each level higher than the cutoff value for positivity set at >99th percentile of normal controls as positive 1.
- The clinical context for testing typically includes unexplained venous or arterial thrombosis, recurrent pregnancy losses, or unexplained thrombocytopenia.
- Positive results may indicate the need for anticoagulation therapy, with the specific regimen depending on the clinical presentation, and low-dose aspirin may be used for primary prevention in asymptomatic individuals with persistent antibodies 1.
Considerations for Testing and Interpretation
- Testing should be performed before starting anticoagulation therapy when possible, as these medications can interfere with lupus anticoagulant testing 1.
- For patients already on anticoagulation, anticardiolipin and anti-β2 glycoprotein I antibodies can still be reliably tested, but interpretation should be done with caution, considering potential interferences from anticoagulant therapy 1.
- The ISTH-SSC subcommittee on lupus anticoagulant/antiphospholipid antibodies recommends against replacing LA with aPS/PT and suggests using aPS/PT and aDI in specific situations, such as when LA testing is unreliable or uncertain 1.
From the Research
Appropriate Workup for Antiphospholipid Antibody (APA) Syndrome
The workup for Antiphospholipid Antibody (APA) Syndrome involves several laboratory tests to detect the presence of antiphospholipid antibodies (aPL). The key tests include:
- Lupus anticoagulant (LA) measurement, which can be complex due to interference from anticoagulant therapy 2
- Anticardiolipin (aCL) and anti-β2-glycoprotein I (β2GPI) antibodies, which are measured using solid-phase assays 3, 4
- Immunoglobulin (Ig) G and IgM isotype testing for aCL and β2GPI antibodies 2
Laboratory Diagnosis
The laboratory diagnosis of APA Syndrome is based on the detection of aPL, which includes:
- LA, aCL, and β2GPI antibodies 3, 4
- Other aPL, such as antibodies against domain I of β2GPI and anti-phosphatidylserine/prothrombin antibodies, may be useful in risk stratification but are not necessary for diagnosis 2, 4
- An integrated interpretation of all test results and an interpretative comment on the laboratory report are essential for accurate diagnosis 2
Challenges and Limitations
The laboratory diagnosis of APA Syndrome is challenging due to:
- Interference from anticoagulant therapy in LA measurement 2
- Variability between different solid-phase assays for aCL and β2GPI antibodies 4
- Lack of universal calibrators or standards for aCL and β2GPI assays 4
- Need for close interaction between clinical pathologists and clinicians to increase diagnostic efficacy and reliability 2
Risk Stratification and Treatment
Risk stratification and treatment of APA Syndrome depend on the presence and type of aPL, as well as the clinical presentation. Patients with triple positivity (LA, aCL, and β2GPI antibodies) are at the highest risk of thrombotic events 3, 5. Treatment options include anticoagulation therapy, such as vitamin K antagonists or direct oral anticoagulants, and immunomodulatory therapies, such as intravenous immunoglobulins 3, 6.