What is Antiphospholipid Antibody Syndrome (APS)?

From the Guidelines

Antiphospholipid antibody syndrome (APS) diagnosis and management should prioritize the accurate detection and interpretation of antiphospholipid antibodies, with lupus anticoagulant, anti-cardiolipin antibodies, and anti-beta2 glycoprotein I antibodies being the cornerstone of laboratory diagnosis, as per the latest guidance from the ISTH-SSC subcommittee on lupus anticoagulant/antiphospholipid antibodies 1.

Key Considerations

• The 2023 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) APS classification criteria remain essentially unchanged compared with the updated Sapporo classification criteria, with aCL and aβ2GPI measurement still restricted to enzyme-linked immunosorbent assays (ELISAs) with moderate and high titer aPL thresholds defined as 40 and 80 Units, respectively 1.
• The use of direct oral anticoagulants (DOACs) in APS is not recommended due to the higher risk of thrombotic events compared to vitamin K antagonists (VKAs) such as warfarin, as evidenced by recent studies 1.
• Treatment of APS typically involves anticoagulation therapy, with the specific regimen depending on clinical presentation, and may include low-dose aspirin, prophylactic-dose low molecular weight heparin, and high-dose corticosteroids in certain cases.

Management Strategies

• For patients with a history of thrombosis, long-term anticoagulation with warfarin (target INR 2.0-3.0) is recommended 1.
• For pregnant women with APS, the standard treatment is low-dose aspirin (81-100 mg daily) plus prophylactic-dose low molecular weight heparin (such as enoxaparin 40 mg daily).
• Patients with catastrophic APS require more aggressive therapy including anticoagulation, high-dose corticosteroids, intravenous immunoglobulin, and sometimes plasma exchange.

Ongoing Considerations

• Regular monitoring of anticoagulation levels is essential, as is addressing modifiable cardiovascular risk factors.
• APS requires lifelong management as the antibodies typically persist, and the risk of recurrent thrombosis remains high without appropriate treatment 1.

From the Research

Definition and Characteristics of Antiphospholipid Antibody Syndrome

• Antiphospholipid antibody syndrome (APS) is an acquired thrombo-inflammatory disorder characterized by thrombosis or pregnancy morbidity, in association with persistent antiphospholipid antibodies (aPL) 2.
• APS can be primary or secondary, with the latter being associated with another autoimmune disorder, most commonly systemic lupus erythematosus 3.
• The syndrome is characterized by the presence of antiphospholipid antibodies (APL) that are directed against phospholipid-binding plasma proteins, such as beta-2-glycoprotein I (b2GPI) 4.

Clinical Manifestations and Diagnosis

• The main manifestations of APS are recurrent vascular thromboses and pregnancy complications 4.
• Diagnosis of APS requires a patient to have both a clinical manifestation (arterial or venous thrombosis and/or pregnancy morbidity) and persistently positive aPL 3.
• Other clinical features, such as thrombocytopenia, Coombs-positive haemolytic anaemia, heart valve disease, renal microangiopathy, and neurologic disorders, are also common in APL-positive patients 4.

Treatment and Management

• Treatment for APS is based on the patient's clinical status, presence of an underlying autoimmune disease, and history of thrombotic events 3.
• Long-term anticoagulation therapy is required to prevent recurrent thrombosis, with warfarin being the mainstay of treatment in APS patients with a prior history of deep venous thrombosis (DVT) 5.
• Other treatment options include subcutaneous low-molecular-weight heparin, unfractionated heparin, or direct oral anticoagulants 5.
• Apixaban, an oral factor Xa inhibitor anticoagulant, may not be routinely substituted for warfarin to prevent recurrent thrombosis, especially strokes, among patients with thrombotic antiphospholipid syndrome (TAPS) 6.

Special Considerations

• In patients with APS on warfarin, the international normalized ratio (INR) may not be representative of anticoagulation intensity due to an interaction between lupus anticoagulant and the thromboplastin reagent used in the INR determination 2.
• Pregnancy complications are usually managed with low-dose aspirin in association with low molecular weight heparin 3.
• Refractory forms of APS could benefit from adding hydroxychloroquine and/or intravenous immunoglobulin to anticoagulation therapy 3.