How to manage a patient with antiphospholipid syndrome?

Management of Antiphospholipid Syndrome

Patients with confirmed antiphospholipid syndrome and thrombosis require lifelong warfarin therapy with target INR 2.0-3.0, and direct oral anticoagulants (DOACs) should be avoided, particularly in triple-positive patients or those with arterial thrombosis. 1, 2

Initial Anticoagulation Strategy

Venous Thromboembolism in APS

• Start warfarin with overlapping parenteral anticoagulation (LMWH or UFH) until INR is therapeutic for at least 24 hours 1, 3
• Target INR of 2.5 (range 2.0-3.0) provides optimal balance between thrombosis prevention and bleeding risk 2, 3
• For first episode of VTE with documented antiphospholipid antibodies, treat for at least 12 months, with indefinite therapy strongly suggested 3
• Lifelong anticoagulation is the standard of care due to high recurrence risk (1.30 per patient-year in the first 6 months after warfarin cessation) 4

Arterial Thrombosis in APS

• Warfarin with target INR 2.0-3.0 plus low-dose aspirin (75-100 mg daily) is recommended 5, 6
• Alternative approach: high-intensity warfarin (INR 3.0-4.0) without aspirin, though this increases bleeding risk 5, 4
• Indefinite anticoagulation is mandatory for arterial events 6

Critical Contraindications

DOACs in APS

• Rivaroxaban is specifically contraindicated in APS, especially in triple-positive patients, due to excess thrombotic events (63 more events per 1,000 cases at 36 months compared to warfarin) 1, 2
• All DOACs should be avoided in high-risk APS patients (triple-positive antibodies, lupus anticoagulant positive, or prior arterial thrombosis) 1, 2, 6
• DOACs may only be considered exceptionally in low-risk venous thrombosis patients who are warfarin-intolerant and LA-negative, though this remains controversial 6, 7

Risk Stratification

High-Risk Features Requiring Aggressive Management

• Triple-positive APS (lupus anticoagulant + anticardiolipin + anti-β2 glycoprotein-I antibodies) represents the highest thrombotic risk 2
• Prior arterial thrombosis 2, 6
• Recurrent thrombotic events 3, 4
• Associated systemic lupus erythematosus 4

Monitoring Considerations

• INR monitoring may be unreliable in LA-positive patients due to interaction between LA and thromboplastin reagent 8
• Consider chromogenic Factor X assay or point-of-care testing when INR results are discordant with clinical picture 8
• Reassess bleeding risk periodically using validated tools, particularly in elderly patients or those with renal/hepatic impairment 9

Special Clinical Scenarios

Perioperative Management

• Stop warfarin 5 days before high-bleeding-risk procedures to achieve INR ≤1.5 1
• Bridge with therapeutic-dose LMWH starting 36 hours after last warfarin dose, with last LMWH dose at half the normal daily dose given 24 hours before surgery 1
• For very high bleeding risk procedures (neurosurgery, cardiovascular surgery), delay resumption of therapeutic LMWH for 48-72 hours postoperatively 1
• Resume warfarin at usual maintenance dose the evening of surgery or next morning once hemostasis is achieved 1

Primary Prophylaxis

• Low-dose aspirin (75-100 mg daily) is recommended for asymptomatic patients with isolated antiphospholipid antibodies who do not meet full APS criteria, especially with additional cardiovascular risk factors 2, 7
• Antiplatelet therapy alone is insufficient for patients with confirmed thrombotic APS 2

Common Pitfalls to Avoid

• Never use moderate-intensity warfarin (INR 2.0-3.0) for only 3 months in APS patients—this is inadequate and leads to high recurrence rates 3, 4
• Avoid high-intensity warfarin (INR 3.0-4.5) routinely, as it provides no additional benefit over moderate intensity for venous thrombosis but significantly increases bleeding risk 2, 3
• Do not test for antiphospholipid antibodies during acute thrombosis; defer testing or repeat at least 4-6 weeks after the acute event and confirm persistence at 12 weeks 2
• Never switch stable APS patients from warfarin to DOACs—this increases thrombotic risk 1, 2

Duration of Therapy

• Indefinite anticoagulation is recommended for all patients with confirmed thrombotic APS 3, 4, 6
• The only exception would be patients with a first venous event, transient reversible risk factors, AND low-risk antibody profile (single positive, low titer), though even these patients warrant extended therapy 5
• Reassess risk-benefit periodically, but discontinuation carries substantial recurrence risk 3