What is Antiphospholipid Syndrome (APS)?

From the Guidelines

Antiphospholipid syndrome (APS) is a thrombo-inflammatory disease driven by antiphospholipid antibodies (aPL) that requires accurate detection and interpretation for diagnosis, with treatment focusing on preventing thrombosis through anticoagulation therapy. The clinical features of APS are not specific and can include recurrent blood clots (thrombosis) and pregnancy complications, making diagnosis dependent on both clinical criteria (vascular thrombosis or pregnancy morbidity) and laboratory criteria (persistent presence of lupus anticoagulant, anticardiolipin antibodies, or anti-β2 glycoprotein-I antibodies) 1.

Key Considerations in APS Diagnosis

• 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, while laboratory detection for APS diagnosis in daily practice is broader and aimed at optimizing patient management 1.
• The 2023 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) APS classification criteria define moderate and high titer aPL thresholds as 40 and 80 Units, respectively, with cutoffs calculated by the 99th percentile abandoned 1.
• Lupus anticoagulant (LA), anti-cardiolipin antibodies (aCL), and anti-beta2 glycoprotein I antibodies (aβ2GPI) remain the cornerstone of the laboratory part of APS diagnosis, with aCL and aβ2GPI measurement restricted to enzyme-linked immunosorbent assays (ELISAs) 1.

Treatment Approaches

• For patients with prior thrombotic events, lifelong warfarin with a target INR of 2.0-3.0 is typically recommended, though direct oral anticoagulants may be considered in certain cases 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), with the addition of hydroxychloroquine (HCQ) conditionally recommended for patients with primary APS 1.
• Patients with catastrophic APS require aggressive treatment with anticoagulation, high-dose corticosteroids, plasma exchange, and/or intravenous immunoglobulin 1.

Monitoring and Management

• Regular monitoring of anticoagulation therapy and awareness of potential complications are essential for effective management of this chronic condition 1.
• The role of immunoglobulin (Ig)M and IgA isotypes, as well as other aPL such as antiphosphatidylserine (aPS)/prothrombin (PT) antibodies, is a matter of ongoing debate and research 1.

From the Research

Overview of Antiphospholipid Syndrome

• Antiphospholipid syndrome (APS) is a rare systemic autoimmune disease characterized by persistent antiphospholipid antibodies (aPL) in combination with recurrent thrombosis in the veins and/or arteries, obstetric morbidity, and various non-thrombotic associated complications 2.
• APS can be primary, as an isolated condition, or secondary in the context of another autoimmune disease, especially systemic lupus erythematosus 2.
• The pathogenesis of APS involves complex interactions between aPL, phospholipid-binding proteins, and the coagulation cascade 2, 3.

Clinical Manifestations

• APS is associated with a wide spectrum of clinical manifestations, including thrombosis, obstetric morbidity, and various non-thrombotic complications 2, 3.
• The cardinal features of APS are thrombosis and APS-related obstetric morbidity 2.
• Diagnosis remains challenging due to overlapping symptoms with other conditions, and clinicians should maintain a high index of suspicion in order to set the diagnosis 2.

Diagnosis

• The recently published 2023 ACR/EULAR criteria offer clinicians a valuable tool to aid in determining whether further investigation for APS is warranted, although they are not definitive for clinical decision-making 2.
• Continued refinement of these criteria through ongoing feedback and updates is anticipated 2.

Treatment

• Anticoagulation is central to the management of APS, with vitamin K antagonists (VKAs) remaining the mainstay of treatment for most patients with thrombotic APS 4, 2, 3.
• The intensity and duration of anticoagulation therapy in APS have been a matter of debate, with recommendations including warfarin to an INR range of 2.0 to 3.0 for patients with a first venous thromboembolic event 5.
• Higher anticoagulation intensity is recommended for patients presenting with arterial events, and combined therapy with warfarin and aspirin is another possibility 5.
• Long-term anticoagulation is considered the standard treatment, although anticoagulation regimes of shorter duration could be given in selected patients with venous thromboembolism who have transient risk factors and a low-risk profile 5.

Management

• Early diagnosis and multidisciplinary management of APS are critical to reducing morbidity and improving outcomes 2.
• Treatment strategies center on anticoagulation, but individualized approaches are necessary 2.
• The potential role of immunomodulatory treatments in APS management is receiving increased attention, with the goal of unlocking personalized and proactive treatments for patients 3.