Who should be started on anticoagulant therapy in Antiphospholipid Syndrome (APLS) positive patients?

Anticoagulation in Antiphospholipid Syndrome (APS) Positive Patients

Who Should Be Started on Anticoagulation

Anticoagulation should be initiated in APS-positive patients who have experienced a thrombotic event (venous or arterial), while asymptomatic patients with positive antibodies alone do not require anticoagulation. 1

Patients Requiring Anticoagulation

Confirmed APS with thrombotic events:

• Patients who meet full diagnostic criteria for APS (persistent positive antibodies on two occasions at least 12 weeks apart) AND have had a documented thrombotic event require anticoagulation 1
• This includes both venous thromboembolism (DVT, PE, cerebral venous thrombosis) and arterial thrombosis (stroke, MI) 2

Specific anticoagulation recommendations:

• Vitamin K antagonist (warfarin) with target INR 2.5 (range 2.0-3.0) is the first-line therapy for patients with confirmed APS and thrombosis 2, 1, 3, 4
• The American College of Chest Physicians recommends adjusted-dose VKA over direct oral anticoagulants (DOACs) during the treatment phase 2
• For venous thrombosis: warfarin with target INR 2.0-3.0 is recommended 1, 5
• For arterial thrombosis: warfarin with target INR 2.0-3.0 or 3.0-4.0 may be considered based on individual bleeding and recurrence risk 5

Patients Who Should NOT Be Started on Anticoagulation

Asymptomatic antibody-positive patients:

• Patients with positive antiphospholipid antibodies but no history of thrombosis or pregnancy morbidity do not require anticoagulation 2
• For cryptogenic stroke or TIA with positive APL antibodies alone, antiplatelet therapy (not anticoagulation) is reasonable 2

Consider low-dose aspirin instead for:

• High-risk antibody profiles (triple-positive, double-positive, isolated lupus anticoagulant, or persistently positive anticardiolipin at medium-high titers) without thrombotic events: low-dose aspirin 75-100mg daily 1
• Non-pregnant adults with history of obstetric APS only (no thrombotic events): low-dose aspirin 75-100mg daily 1

Critical Treatment Algorithm

Step 1: Confirm APS Diagnosis

• Requires both clinical criteria (thrombosis or pregnancy morbidity) AND laboratory criteria (persistent positive antibodies on two occasions ≥12 weeks apart) 1

Step 2: Classify Thrombotic Event Type

• Venous thrombosis: Start warfarin targeting INR 2.0-3.0 1, 4, 5
• Arterial thrombosis: Start warfarin targeting INR 2.0-3.0, consider adding low-dose aspirin 75-100mg daily 1, 5
• Stroke/TIA with full APS criteria: Warfarin with target INR 2.0-3.0 2
• Cryptogenic stroke with positive antibodies but NOT meeting full APS criteria: Antiplatelet therapy (aspirin), not anticoagulation 2

Step 3: Determine Duration

• First venous thrombosis: Minimum 3 months, consider indefinite therapy for idiopathic events 4
• Arterial thrombosis or recurrent events: Indefinite anticoagulation 4, 5
• Patients with documented antiphospholipid antibodies and first thrombosis: 12 months recommended, indefinite therapy suggested 4

Critical Pitfalls to Avoid

Never use DOACs in high-risk APS patients:

• Direct oral anticoagulants (rivaroxaban, apixaban, etc.) are contraindicated in triple-positive APS patients due to increased risk of recurrent thrombosis compared to warfarin 1, 3, 6, 5
• The FDA label for rivaroxaban explicitly warns against use in triple-positive antiphospholipid syndrome 6
• DOACs should be avoided in patients with arterial thrombosis and/or triple aPL positivity 5
• Some evidence suggests DOACs may be acceptable only in single-positive APS patients, but this remains controversial and warfarin is preferred 7

Do not anticoagulate based on antibodies alone:

• The WARSS/APASS study showed no difference in recurrent stroke rates between warfarin and aspirin in APL-positive patients, and overall event rates were similar between APL-positive and APL-negative patients 2
• Asymptomatic antibody positivity alone is not an indication for anticoagulation 2

Avoid estrogen-containing contraceptives:

• Strongly contraindicated in women with positive antiphospholipid antibodies due to significantly increased thrombosis risk 1

Special Populations

Pregnancy:

• Use low molecular weight heparin plus low-dose aspirin throughout pregnancy, NOT warfarin (teratogenic in first trimester) 1, 3
• Prophylactic anticoagulation with LMWH is recommended for aPL-positive patients undergoing assisted reproductive technology 1

Cerebral venous thrombosis:

• Initiate anticoagulation immediately with LMWH or unfractionated heparin, then transition to warfarin targeting INR 2.0-3.0 3
• Anticoagulation should be initiated even with hemorrhagic transformation 3

Treatment-refractory APS:

• Consider adding antiplatelet therapy to anticoagulation 1
• Hydroxychloroquine may be added, especially in patients with underlying systemic lupus erythematosus 1, 3