From the Guidelines
The recommended treatment for patients with Antiphospholipid Syndrome (APS) primarily involves anticoagulation therapy with adjusted dose vitamin K antagonists (VKA) such as warfarin, targeting an INR of 2.5, over direct oral anticoagulant (DOAC) therapy during the treatment phase. This recommendation is based on the most recent and highest quality study available, which suggests that VKA therapy is more effective in preventing thrombotic events compared to DOAC therapy in patients with APS 1.
Key Considerations
- For patients with thrombotic APS who have experienced a venous thromboembolism, long-term anticoagulation with VKA is recommended, with a target INR of 2.0-3.0.
- For arterial thrombosis, a higher intensity anticoagulation (INR 3.0-4.0) or combination therapy with warfarin plus low-dose aspirin (75-100 mg daily) may be used.
- For pregnant women with APS, the standard treatment includes prophylactic low molecular weight heparin (such as enoxaparin 40 mg daily) plus low-dose aspirin throughout pregnancy and for 6 weeks postpartum.
- Patients with catastrophic APS require more aggressive treatment including therapeutic anticoagulation, high-dose corticosteroids (methylprednisolone 1000 mg daily for 3 days), intravenous immunoglobulin (2 g/kg over 5 days), and sometimes plasma exchange.
- For patients with persistent antiphospholipid antibodies but no prior thrombotic events (primary prophylaxis), low-dose aspirin may be considered, especially with additional cardiovascular risk factors.
Rationale
The rationale for anticoagulation is that antiphospholipid antibodies promote a hypercoagulable state by activating endothelial cells, platelets, and the complement system, leading to thrombosis formation. The use of VKA therapy has been shown to be effective in preventing thrombotic events in patients with APS, and is therefore recommended as the primary treatment option 1.
Additional Considerations
- The presence of antiphospholipid antibodies is associated with thrombotic and obstetric complications and increased risk of damage accrual 1.
- Low-dose aspirin may be considered for primary prophylaxis against thrombosis in patients with APS, especially those with additional cardiovascular risk factors.
- The optimal duration and timing of discontinuation of therapy in both renal and cardiovascular disease are still unknown and require further study.
From the FDA Drug Label
For patients with a first episode of DVT or PE who have documented antiphospholipid antibodies or who have two or more thrombophilic conditions, treatment for 12 months is recommended and indefinite therapy is suggested
- The recommended treatment for patients with antiphospholipid antibodies is warfarin for 12 months, with indefinite therapy suggested.
- The dose of warfarin should be adjusted to maintain a target INR of 2.5 (INR range, 2.0 to 3.0) for all treatment durations 2.
From the Research
Treatment Overview
The treatment of antiphospholipid syndrome (APS) typically involves anticoagulation therapy to prevent recurrent thrombosis. The mainstay of anticoagulation in patients with thrombotic APS is warfarin or an alternative vitamin K antagonist (VKA) and, in certain situations, low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) 3.
Anticoagulation Therapy
- Warfarin is commonly used for long-term anticoagulation in patients with APS, with a target international normalized ratio (INR) of 2.0-3.0 4, 5, 6.
- High-intensity warfarin (INR > 3) with or without low-dose aspirin may be more effective in preventing further thrombotic events than low-intensity warfarin or aspirin alone 5.
- New oral anticoagulants (NOACs) such as dabigatran, rivaroxaban, apixaban, and edoxaban may be considered as alternatives to warfarin, but their use in APS requires further study 7.
Monitoring and Adjustment
- Accurate assessment of anticoagulation intensity is crucial for optimal anticoagulant dosing, and point-of-care INR monitoring may be useful in patients with APS on warfarin 3.
- Antiphospholipid antibodies may interfere with INR determination, requiring alternative approaches to monitor and adjust warfarin dose 3, 6.
Prevention of Recurrent Thrombosis
- Long-term anticoagulation is recommended to prevent recurrent venous thrombosis in patients with APS 5, 6.
- Low-dose aspirin may be recommended for primary prevention of thrombosis in asymptomatic patients with moderate to high levels of antiphospholipid antibodies, although strong supporting data are lacking 6.