What is Antiphospholipid Syndrome (APS)?

From the Guidelines

Antiphospholipid syndrome (APS) diagnosis and management should prioritize the detection and interpretation of antiphospholipid antibodies, with lupus anticoagulant, anti-cardiolipin antibodies, and anti-beta2 glycoprotein I antibodies remaining the cornerstone of laboratory diagnosis, as recommended by the 2023 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria 1.

Diagnosis and Classification

The diagnosis of APS is dependent on the accurate detection and interpretation of antiphospholipid antibodies (aPL) 1. The 2023 ACR/EULAR classification criteria define the type of laboratory parameters, including lupus anticoagulant (LA), anti-cardiolipin antibodies (aCL), and anti-beta2 glycoprotein I antibodies (aβ2GPI), which remain the cornerstone of the laboratory part of APS diagnosis 1.

• The measurement of aCL and aβ2GPI is restricted to enzyme-linked immunosorbent assays (ELISAs) with moderate and high titer aPL thresholds defined as 40 and 80 Units, respectively 1.
• The cutoff calculated by the 99th percentile has been abandoned in the 2023 ACR/EULAR classification criteria 1.

Management

Treatment of APS primarily focuses on preventing thrombosis through anticoagulation therapy.

• For patients with a history of thrombosis, long-term warfarin with a target INR of 2.0-3.0 is typically recommended, though some evidence suggests a higher target INR of 3.0-4.0 may be beneficial for those with recurrent thrombosis despite standard anticoagulation 1.
• For pregnant women with APS, the standard regimen includes low-dose aspirin (81-100 mg daily) plus prophylactic low molecular weight heparin (such as enoxaparin 40 mg daily or equivalent).
• Patients with APS but no history of thrombosis may be managed with low-dose aspirin alone for primary prevention.
• During acute thrombotic events, initial treatment with unfractionated or low molecular weight heparin followed by transition to warfarin is recommended.
• Newer direct oral anticoagulants (DOACs) are generally not recommended for APS, particularly in high-risk patients with triple-positive antibody status, as studies have shown increased thrombotic risk compared to warfarin 1.

Monitoring and Education

Regular monitoring of anticoagulation therapy is essential, and patients should be educated about the importance of medication adherence and recognizing signs of thrombosis or bleeding complications.

• 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, aimed at optimizing patient management 1.

From the Research

Definition and Characteristics of Antiphospholipid Syndrome

• Antiphospholipid syndrome (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 2.
• APS is characterized by thrombosis (venous, arterial, or microvascular) or pregnancy morbidity, in association with persistent antiphospholipid antibodies (aPL) 3.
• The syndrome can cause various clinical manifestations, including livedo reticularis, cutaneous ulcerations, thrombocytopenia, hemolytic anemia, valvular heart disease, and nephropathy 4.

Diagnosis and Treatment of Antiphospholipid Syndrome

• The diagnosis of APS appears to affect at least one in 2000 people, and vitamin K antagonists remain the mainstay of treatment for most patients with thrombotic antiphospholipid syndrome 5.
• Current standard treatment for unprovoked thrombosis is long-term warfarin or other vitamin K antagonist therapy, while treatment to prevent recurrent obstetric complications is low-dose aspirin and prophylactic heparin, usually low-molecular-weight heparin 4.
• Direct oral anticoagulant drugs may not be suitable for high-risk patients with thrombotic APS, and emerging evidence suggests that immunomodulating agents, statins, and novel agents such as sirolimus and defibrotide may be potential alternatives 2.

Monitoring and Management of Anticoagulation Therapy

• Accurate assessment of anticoagulation intensity is crucial for optimal anticoagulant dosing in patients with APS, and point-of-care testing (POCT) to monitor INR is discouraged in patients with APS due to potential interactions between antiphospholipid antibodies and thromboplastin used for INR testing 3, 6.
• However, a study found that POCT management of APS showed comparable results to venous INR monitoring, suggesting that POCT may be a viable option for monitoring INR control in patients with APS 6.
• The role and monitoring of low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) are also important in the management of APS, particularly in certain situations such as pregnancy or anticoagulant refractory settings 3.