Antiphospholipid Antibody Syndrome With Thrombosis

Thrombotic antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilia with venous, arterial or small vessel thrombosis and persistently positive antiphospholipid antibodies.

• Antibodies: lupus anticoagulant (strongest predictor), anticardiolipin IgG/IgM, anti beta-2 glycoprotein I IgG/IgM. Triple positivity carries the highest risk.

• Primary or associated with SLE (secondary, 30 to 40% of SLE patients have antibodies).

• Venous thromboembolism (deep vein, pulmonary embolism, cerebral venous, Budd Chiari), arterial events (stroke, TIA, myocardial infarction), recurrent thrombosis despite treatment.

• Other manifestations: livedo reticularis, thrombocytopenia, valvular disease, nephropathy, cognitive impairment.

• Unprovoked or recurrent venous thrombosis, stroke or TIA in young adults, myocardial infarction.

• Livedo racemosa, skin ulcers, digital gangrene.

• Cardiac valve thickening (Libman-Sacks), nephropathy, adrenal haemorrhage.

• Catastrophic APS is a separate emergency.

• Sydney/2023 ACR-EULAR classification: clinical event (thrombosis, obstetric) and laboratory criteria on two occasions at least 12 weeks apart.

• Lupus anticoagulant by two tests (dRVVT, aPTT-based), measured before anticoagulation where possible (DOACs and heparin interfere); anticardiolipin and anti beta-2 GPI IgG/IgM above 40 units or 99th percentile.

• Platelet count, aPTT, ANA, anti-dsDNA, complements, echocardiography, renal function, brain imaging.

• Evaluate other thrombotic risks.

• Acute thrombosis: heparin (UFH or enoxaparin 1 mg/kg twice daily), transition to warfarin.

• Long-term anticoagulation with warfarin INR 2.0 to 3.0 for venous thrombosis (lifelong in most). Avoid DOACs (rivaroxaban inferior in triple positive and arterial disease).

• Arterial thrombosis: warfarin with INR 2.0 to 3.0 (some guidelines advise 3.0 to 4.0 or combination with aspirin 75 to 100 mg for high-risk patients); individualise.

• Recurrent thrombosis on adequate anticoagulation: raise INR target to 3.0 to 4.0, add aspirin or switch to LMWH (enoxaparin 1 mg/kg twice daily), add hydroxychloroquine 200 to 400 mg daily, statin; consider rituximab, eculizumab, or sirolimus in refractory cases.

• Thrombocytopenia: steroids, IVIG; avoid platelet infusion.

• Primary prophylaxis in asymptomatic high-risk carriers: aspirin 75 to 100 mg daily, hydroxychloroquine in SLE; cardiovascular risk control, avoid oestrogen contraception.

• Pregnancy: therapeutic LMWH throughout and 6 weeks postpartum for prior thrombosis; warfarin is teratogenic (avoid 6 to 12 weeks).

• Monitor INR (point of care/chromogenic Factor X because of lupus anticoagulant interference).