What are Antiphospholipid Syndrome (APS)?

From the Guidelines

Antiphospholipid syndrome (APS) is a thrombo-inflammatory disease driven by antiphospholipid antibodies (aPL) that increase the risk of thrombosis, pregnancy morbidity, and other autoimmune and inflammatory manifestations. The diagnosis of APS is dependent on accurate detection and interpretation of aPL, including lupus anticoagulant (LA), anti-cardiolipin antibodies (aCL), and anti-beta2 glycoprotein I antibodies (aβ2GPI) 1.

Key Characteristics of APS

• APS is characterized by the presence of antiphospholipid antibodies that bind to phospholipid-binding proteins, activating endothelial cells, platelets, and the complement system, leading to a hypercoagulable state 1
• The clinical features of APS are not specific and can include thrombosis, pregnancy complications, and other autoimmune and inflammatory manifestations 1
• The diagnosis of APS requires the detection and interpretation of aPL, which can be done using various laboratory tests, including enzyme-linked immunosorbent assays (ELISAs) 1

Laboratory Detection and Interpretation of aPL

• The 2023 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) APS classification criteria define the type of laboratory parameters used for APS diagnosis, including LA, aCL, and aβ2GPI 1
• The measurement of aCL and aβ2GPI is restricted to ELISAs, with moderate and high titer thresholds defined as 40 and 80 Units, respectively 1
• The role of other aPL, such as antiphosphatidylserine (aPS)/prothrombin (PT) antibodies, and the use of non-ELISA assays are areas of ongoing research and debate 1

Clinical Implications

• The accurate detection and interpretation of aPL are critical for the diagnosis and management of APS, and clinicians must differentiate between classification criteria and assessment of aPL in clinical care 1
• Patients with APS require lifelong management, and discontinuation of anticoagulation typically results in recurrent thrombotic events 1
• The treatment of APS involves anticoagulation therapy, and the choice of treatment depends on the individual patient's risk factors and clinical presentation 1

From the Research

Definition of Antiphospholipid Syndrome (APS)

• Antiphospholipid Syndrome (APS) is an acquired thrombo-inflammatory disorder characterized by thrombosis (venous, arterial, or microvascular) or pregnancy morbidity, in association with persistent antiphospholipid antibodies (aPL) 2.
• APS is an acquired autoimmune disorder characterized by thrombosis, pregnancy morbidity, and the presence of antiphospholipid antibodies (aPL) 3.
• The syndrome is defined by the occurrence of venous and/or arterial thrombosis and/or pregnancy-related morbidity, combined with the presence of antiphospholipid antibodies (aPL) and/or a lupus anticoagulant (LAC) 4.
• APS is a systemic autoimmune disorder characterized by recurrent venous or arterial thrombosis with or without pregnancy morbidity in the presence of persistent antiphospholipid (aPL) autoantibodies 5.

Characteristics of APS

• Thrombosis is the most common manifestation of APS, and can occur in virtually any vascular bed, with cerebral circulation being the arterial territory most commonly affected 3.
• The presence of antiphospholipid antibodies (aPL) is a key characteristic of APS, and can be detected through laboratory tests 4.
• APS is a heterogeneous condition, and its management should be tailored with a patient-centred approach based on individual risk assessment, which includes the aPL profile, concomitant auto-immune diseases, and traditional cardiovascular risk factors 3.

Diagnosis and Treatment of APS

• The diagnosis of APS includes the combination of thrombotic events and presence of aPL 4.
• Treatment with vitamin K-antagonists (VKA) with INR 2.0-3.0 is first-line treatment for a first or recurrent APS-related venous thrombotic event 4.
• Patients with first arterial thrombosis should be treated with clopidogrel or VKA with target INR 2.0-3.0 4.
• Anticoagulation has, until now, formed the cornerstone of treatment for APS, but a significant proportion of patients continue to experience thrombosis and pregnancy morbidity despite this treatment 5.