What are the guidelines for Antiphospholipid Syndrome (APS) from the American Society of Hematology (ASH)?

From the Guidelines

The American Society of Hematology (ASH) guidelines for antiphospholipid syndrome (APS) recommend anticoagulation as the primary treatment approach, with a target INR of 2.0-3.0 for patients with thrombotic APS who experience a first venous thromboembolism, as supported by the most recent guidelines from the American Heart Association/American Stroke Association 1.

Key Recommendations

• For patients with thrombotic APS who experience a first venous thromboembolism, indefinite anticoagulation with vitamin K antagonists (such as warfarin) is recommended, targeting an INR of 2.0-3.0 1.
• For patients with arterial thrombosis, the guidelines suggest either vitamin K antagonists with an INR target of 2.0-3.0 or a higher intensity anticoagulation with an INR target of 3.0-4.0 1.
• Direct oral anticoagulants (DOACs) are not recommended for patients with triple-positive APS or those with arterial thrombosis, as they are associated with excess thrombotic events compared to warfarin 1.
• For pregnant women with APS and recurrent pregnancy loss, combination therapy with low-dose aspirin (81-100 mg daily) and prophylactic-dose heparin (either unfractionated heparin or low molecular weight heparin such as enoxaparin 40 mg daily) is recommended 1.

Laboratory Detection and Interpretation

• The diagnosis of APS is dependent on the accurate detection and interpretation of antiphospholipid antibodies (aPL), including lupus anticoagulant (LA), anti-cardiolipin antibodies (aCL), and anti-beta2 glycoprotein I antibodies (aβ2GPI) 1.
• The 2023 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) APS classification criteria define moderate and high titer thresholds as 40 and 80 Units, respectively, with cutoffs calculated by the 99th percentile abandoned 1.

Clinical Considerations

• 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.
• The method endorsed by the ISTH Guidance and Guidelines Committee Panel on writing guidance is applied, with the wording “recommend” indicating a strong consensus among the coauthors, “suggest” indicating a moderate consensus, and “propose” indicating areas where there is limited knowledge 1.

From the Research

Guidelines for Antiphospholipid Syndrome (APS)

The American Society of Hematology (ASH) guidelines for Antiphospholipid Syndrome (APS) are as follows:

• Diagnosis of APS includes the combination of thrombotic events and presence of antiphospholipid antibodies (aPL) 2
• Risk stratification on an individual basis remains challenging, with 'triple positive' patients having the highest risk of recurrent thrombosis 2
• 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 2
• Patients with first arterial thrombosis should be treated with clopidogrel or VKA with target INR 2.0-3.0 2
• Treatment with direct oral anticoagulants is not recommended 2, 3
• Patients with catastrophic APS, recurrent thrombotic events, or recurrent pregnancy morbidity should be referred to an expert centre 2

Management of APS

The management of APS 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 4

• Antiplatelet agents may reduce the risk of a first thrombotic event in individuals with a high-risk profile 4
• Lifelong vitamin K antagonists (VKAs), preferably warfarin, are recommended for patients with thrombotic APS 4
• The optimal intensity of anticoagulation following arterial thrombosis remains controversial, with options including high-intensity warfarin at a target INR > 3.0, or low-dose aspirin (LDA) combined with moderate-intensity warfarin (INR 2.0-3.0) 4

Treatment Options

Treatment options for APS include:

• Vitamin K antagonists (VKAs) with INR 2.0-3.0 2
• Clopidogrel or VKA with target INR 2.0-3.0 for first arterial thrombosis 2
• Low-molecular-weight-heparin, fondaparinux, and/or the addition of antiplatelet treatment for recurrent thrombosis and anticoagulant-refractory APS 5
• Adjunctive options such as vitamin D, hydroxychloroquine, and statins may also be considered 5