What is Antiphospholipid Syndrome (APS)?

From the Guidelines

Antiphospholipid syndrome (APS) is a thrombo-inflammatory disease driven by antiphospholipid antibodies (aPL) that increase the risk of blood clots, pregnancy complications, and other autoimmune and inflammatory manifestations. The diagnosis of APS is dependent on the 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 recognize phospholipid surfaces and phospholipid-binding proteins, leading to thrombosis and other clinical manifestations 1.
• The clinical features of APS are not specific and can include thrombosis, pregnancy morbidity, and other autoimmune and inflammatory manifestations 1.
• The diagnosis of APS requires the accurate detection and interpretation of aPL, which can be achieved through laboratory tests such as 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 recommend the use of LA, aCL, and aβ2GPI as the cornerstone of laboratory diagnosis, with moderate and high titer thresholds defined as 40 and 80 Units, respectively 1.
• The measurement of aCL and aβ2GPI is restricted to ELISAs, and the use of non-ELISA assays is increasing, with semiquantitative reporting of titers and the role of immunoglobulin (Ig)M and IgA isotypes being debated 1.

Clinical Implications

• The distinction between classification criteria and assessment of aPL in clinical care is critical, as classification criteria are strict and meant for participant inclusion in studies and trials, while laboratory detection for APS diagnosis in daily practice is broader and meant to diagnose each APS patient to optimize their management 1.
• Patients with APS may require anticoagulation therapy to prevent thrombosis, and the choice of anticoagulant and intensity of therapy should be individualized based on the patient's risk factors and clinical presentation 1. The management of APS should prioritize the prevention of thrombosis and pregnancy complications, and patients should be educated about the lifelong nature of their condition and the importance of medication adherence and specialized care during high-risk periods.

From the Research

Definition and Characteristics 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 diagnosis of APS is made by the persistent detection of anticardiolipin antibodies, β2-glycoprotein I antibodies (β2GPIA), and/or lupus anticoagulants (LAs) for at least 12 weeks, along with at least one clinical and one laboratory criterion 4.

Clinical Manifestations 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.
• Venous thromboembolism is the most common manifestation of APS 3.
• Pregnancy morbidity is also a common manifestation of APS, and can include recurrent miscarriages and other complications 2, 3.

Treatment and Management of APS

• Anticoagulation is central to the management of APS, and the mainstay of anticoagulation in patients with thrombotic APS is warfarin or an alternative vitamin K antagonist (VKA) 2, 3.
• Direct oral anticoagulants (DOACs) may be considered in patients with low-risk APS, but are not recommended for high-risk patients with arterial APS or triple positivity 5, 4.
• Aspirin can be given as primary prevention in asymptomatic patients with positive antiphospholipid antibodies without thrombosis or pregnancy complications, especially when additional vascular risk factors are present 4.