What is the primary treatment for antiphospholipid syndrome (APS)?

Primary Treatment for Antiphospholipid Syndrome (APS)

For patients with confirmed antiphospholipid syndrome requiring anticoagulant therapy, adjusted-dose vitamin K antagonists (VKAs) with a target INR of 2.5 (range 2.0-3.0) are recommended over direct oral anticoagulants (DOACs). 1

Diagnosis and Risk Stratification

APS is diagnosed based on:

• Clinical criteria: Thrombosis (venous, arterial, or microvascular) and/or pregnancy morbidity
• Laboratory criteria: Persistent presence of antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies, or anti-β2-glycoprotein-I antibodies)

Risk stratification is essential:

• High-risk patients: Triple-positive antibody profile (positive for all three antibodies) or arterial thrombosis
• Standard-risk patients: Single or double antibody positivity with venous thrombosis

Treatment Algorithm for Thrombotic APS

1. Initial Treatment

• Begin with parenteral anticoagulation (LMWH or UFH) overlapping with VKA initiation 1
• Continue parenteral anticoagulation until therapeutic INR is achieved (2.0-3.0)

2. Long-term Anticoagulation

• First-line therapy: Vitamin K antagonists (warfarin) with target INR 2.0-3.0 1, 2
• Duration: Lifelong anticoagulation is recommended as long as antiphospholipid antibodies persist 2, 3

3. Special Situations

Venous Thromboembolism (VTE)

• Standard-intensity warfarin (INR 2.0-3.0) 1, 3
• DOACs should be avoided, especially in high-risk patients 1, 2, 3

Arterial Thrombosis

Two options:

• High-intensity warfarin (INR >3.0) 3, 4
• OR moderate-intensity warfarin (INR 2.0-3.0) plus low-dose aspirin (75-100 mg/day) 2, 3

Recurrent Thrombosis Despite Therapeutic INR

• Increase target INR to 3.0-4.0 2, 4
• Add low-dose aspirin if not already prescribed 2
• Consider adding hydroxychloroquine, especially in patients with SLE 2, 5

Catastrophic APS (CAPS)

Triple therapy approach:

• Therapeutic anticoagulation
• High-dose glucocorticoids
• Plasma exchange and/or intravenous immunoglobulins 2

Obstetric APS Management

For pregnant women with APS:

• Low-dose aspirin plus prophylactic LMWH 2, 3
• Avoid warfarin during pregnancy (teratogenic) 2
• Continue treatment throughout pregnancy and 6 weeks postpartum

Primary Thromboprophylaxis

For asymptomatic individuals with persistent antiphospholipid antibodies:

• Low-dose aspirin (75-100 mg/day), especially with additional cardiovascular risk factors 2, 6
• Aggressive management of traditional cardiovascular risk factors 2

Monitoring and Follow-up

• Regular INR monitoring (more frequent initially, then every 4-6 weeks when stable)
• Periodic reassessment of antiphospholipid antibody status
• Annual assessment of thrombotic risk factors
• Regular evaluation for potential complications

Important Caveats

• DOACs (apixaban, dabigatran, edoxaban, rivaroxaban) should be avoided in APS patients, especially those who are triple-positive for antiphospholipid antibodies or have arterial thrombosis 1, 2
• Initiating VKA therapy must include an overlapping period of parenteral anticoagulation 1
• Discontinuation of anticoagulation might be considered only in very selected low-risk patients whose antiphospholipid antibodies have become persistently negative 7, but this approach requires careful consideration and is not standard practice

The evidence strongly supports the use of vitamin K antagonists as the cornerstone of APS management, with treatment decisions guided by the patient's specific thrombotic risk profile and antibody status.