Treatment and Prophylaxis of Antiphospholipid Antibody Syndrome (APLA)
Primary Prevention in Asymptomatic APLA-Positive Patients
For asymptomatic patients with positive antiphospholipid antibodies and no prior thrombotic events, do NOT routinely use anticoagulation or aspirin for primary prevention, as the APLASA trial demonstrated no benefit of aspirin over placebo (HR 1.04,95% CI 0.69-1.56, P=0.83) and the bleeding risk of therapeutic anticoagulation outweighs the low absolute thrombotic risk. 1
The annual thrombosis incidence in asymptomatic APLA-positive individuals is low, and vascular events typically occur only when additional thrombotic risk factors are present. 1
Exception: Consider low-dose aspirin (75-100 mg daily) in asymptomatic APLA-positive patients who also have systemic lupus erythematosus (SLE), as meta-analysis data support a protective role in this specific subgroup. 1
Triple-positive antibodies (lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein I) confer higher risk with annual thrombosis incidence of 5.3% versus 1.9% for single positive tests, but this still does not justify routine anticoagulation in the absence of thrombotic events. 1
Secondary Prevention After Thrombotic Events
Venous Thromboembolism
For patients with APLA and a first venous thrombotic event, initiate warfarin with a target INR of 2.0-3.0 for long-term anticoagulation. 2, 1
For first episode of venous thrombosis with documented antiphospholipid antibodies, treat with warfarin for at least 12 months, with indefinite therapy strongly suggested due to high recurrence risk. 2
For patients with two or more episodes of documented venous thromboembolism, indefinite treatment with warfarin is recommended. 2
The risk of recurrent thrombosis after warfarin discontinuation is significantly elevated in APLA patients, supporting the standard of long-term anticoagulation. 3, 4
Arterial Thromboembolism
For patients with APLA and arterial thrombosis (including stroke or TIA), use higher-intensity anticoagulation with warfarin targeting INR 3.0-4.0, as 40% of thromboembolic events in APLA-positive patients are arterial. 1, 5
- Combined therapy with warfarin (INR 2.0-3.0) plus low-dose aspirin (75-100 mg daily) is an alternative approach for arterial events, though higher-intensity warfarin monotherapy is preferred by most guidelines. 5, 4
Obstetric APLA Syndrome
During Pregnancy
For pregnant women with obstetric APLA syndrome (recurrent pregnancy loss), use prophylactic or intermediate-dose low-molecular-weight heparin (LMWH) or unfractionated heparin combined with low-dose aspirin (75-100 mg daily) throughout pregnancy. 6, 1
For women who fulfill laboratory criteria for APLA syndrome with three or more miscarriages before 10 weeks of gestation, this combination therapy is the standard of care. 6
Continue anticoagulation postpartum for 6 weeks with prophylactic- or intermediate-dose LMWH or vitamin K antagonists targeted at INR 2.0-3.0. 6
Outside Pregnancy
For women with obstetric APLA syndrome outside of pregnancy, use prophylactic low-dose aspirin (75-100 mg daily). 1
Monitoring and Special Considerations
Anticoagulation Monitoring
Lupus anticoagulant can interfere with phospholipid-dependent coagulation monitoring tests (PT/INR), potentially causing spurious results that do not reflect true anticoagulation intensity. 7
In patients with lupus anticoagulant, consider alternative monitoring strategies including anti-Xa levels for heparin therapy or chromogenic factor X assays for warfarin monitoring when INR results are unreliable. 7
High-Risk Features Requiring Intensified Therapy
Triple-positive antibody profile (lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein I) warrants more intensive anticoagulation and closer monitoring. 1
Recurrent thrombotic events despite therapeutic anticoagulation may require escalation to higher-intensity warfarin (INR 3.0-4.0) or addition of antiplatelet therapy. 5, 4
Duration of Therapy
Reassess the risk-benefit ratio periodically in patients receiving indefinite anticoagulation, though most APLA patients with thrombotic events require lifelong therapy. 2
Anticoagulation discontinuation may be considered only in highly selected low-risk primary APLA patients whose antiphospholipid antibodies become persistently negative over time, though this requires careful monitoring. 8
Critical Pitfalls to Avoid
Do not use direct oral anticoagulants (DOACs) as first-line therapy in APLA patients with thrombotic events, as evidence for their efficacy and safety in this population is lacking and recent guidance does not support their routine use. 7
Do not delay anticoagulation in confirmed thrombotic APLA syndrome while attempting to achieve "perfect" INR monitoring, as the thrombotic risk is immediate and substantial. 3
Do not use antithrombotic prophylaxis in women with inherited thrombophilia and pregnancy complications who do not have APLA, as this is not supported by evidence. 6
Do not screen for inherited thrombophilia in women with pregnancy complications, as APLA screening is what matters for obstetric APS. 6
Risk Factor Modification
Aggressively minimize all modifiable vascular risk factors in all APLA patients, including smoking cessation, diabetes control, hypertension management, and lipid optimization, as these additional risk factors significantly increase thrombotic risk. 1, 5