From the Guidelines
Antiphospholipid syndrome (APLS) antibodies primarily include three main types: lupus anticoagulant (LA), anticardiolipin antibodies (aCL), and anti-β2 glycoprotein I antibodies (anti-β2GPI), as emphasized in the 2025 guidance from the ISTH-SSC subcommittee on lupus anticoagulant/antiphospholipid antibodies 1. These antibodies target phospholipids and phospholipid-binding proteins, disrupting normal coagulation processes. Lupus anticoagulant paradoxically increases clotting risk despite prolonging clotting tests in the laboratory. Anticardiolipin antibodies bind to cardiolipin, a phospholipid found in cell membranes, particularly when complexed with β2-glycoprotein I. Anti-β2GPI antibodies directly target the β2-glycoprotein I protein, which plays a role in regulating coagulation. For APLS diagnosis, persistent positivity (at least 12 weeks apart) for one or more of these antibodies is required, along with clinical manifestations such as thrombosis or pregnancy complications, as stated in the 2023 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) APS classification criteria 1. Testing for all three antibody types is recommended as some patients may be positive for only one type, and the antibody profile helps determine thrombotic risk and guides treatment decisions regarding anticoagulation therapy. Key considerations in the interpretation of these antibodies include the distinction between classification criteria for research purposes and diagnostic assessment in clinical practice, with the latter being broader and aimed at optimizing patient care 1. Additionally, the role of other antiphospholipid antibodies, such as antiphosphatidylserine (aPS)/prothrombin (PT) antibodies, and the significance of immunoglobulin (Ig)M and IgA isotypes, are areas of ongoing study and debate in the context of APLS diagnosis and management 1.
From the Research
APLS Antibody Types
The antiphospholipid syndrome (APS) is characterized by the presence of antiphospholipid antibodies (aPL) that are directed against phospholipid-binding plasma proteins, such as beta-2-glycoprotein I (b2GPI) 2. The main types of aPL include:
- Lupus anticoagulants (detected using clotting assays)
- Anticardiolipin antibodies (detected by ELISA)
- Anti-β2-glycoprotein I antibodies (detected by ELISA)
- Anti-prothrombin/phosphatidylserine antibodies (detected by ELISA) 3
Antibody Specificities
Each of these aPL may be either IgG, IgM, or IgA, though IgA antibodies are not included in criteria for APS 3. The presence of antiphospholipid antibodies can be completely asymptomatic, or they can lead to clinical manifestations as severe as catastrophic antiphospholipid syndrome 4.
Clinical Manifestations
Associated clinical manifestations include livedo reticularis, cutaneous ulcerations, thrombocytopenia, hemolytic anemia, valvular heart disease, and nephropathy 5. The degree of risk associated with antiphospholipid antibody depends on the characteristics of the antiphospholipid antibody profile and on the presence of additional thrombotic risk factors 4, 5.
Thrombotic Risk Stratification
Thrombosis risk stratification is challenging due to the relative rarity of APS and the heterogeneity of aPL 3. Patients with all three aPL (triple positive) are at highest risk of both a first thrombotic event and of a recurrence, despite anticoagulation 6.