Key Facts

APS is the most common acquired thrombophilia. Early recognition prevents recurrent thrombosis and adverse pregnancy outcomes.

Epidemiology

• Antiphospholipid antibodies found in 1-5% of healthy population
• APS develops in ~30-40% of SLE patients
• Primary APS (no underlying autoimmune disease): ~50% of cases
• F:M 5:1 for secondary (SLE-associated); more equal for primary

Pathophysiology

• Antiphospholipid antibodies bind β2-glycoprotein I on endothelial cells, platelets, and trophoblasts
• Endothelial activation → tissue factor expression → thrombosis
• Complement activation (particularly classical pathway)
• Placental thrombosis and inflammation → obstetric complications
• Lupus anticoagulant inhibits phospholipid-dependent coagulation in vitro (prolonged APTT) but is prothrombotic in vivo

Thrombotic APS

• Venous (most common): DVT, PE, cerebral venous sinus thrombosis, Budd-Chiari, renal vein thrombosis
• Arterial: stroke/TIA (especially young), MI, mesenteric ischaemia, digital gangrene
• Livedo reticularis: mottled, net-like skin pattern (common)
• Thrombocytopenia: mild (50-100 × 10⁹/L); rarely causes bleeding
• Libman-Sacks endocarditis: sterile vegetations on valve leaflets
• Sneddon syndrome: livedo reticularis + cerebrovascular disease

Obstetric APS

• ≥3 unexplained consecutive miscarriages <10 weeks
• ≥1 unexplained fetal death ≥10 weeks (morphologically normal fetus)
• ≥1 premature delivery <34 weeks due to eclampsia/pre-eclampsia/placental insufficiency

Catastrophic APS (CAPS)

• Multiorgan thrombosis developing rapidly (days-weeks)
• ≥3 organ systems involved
• Microangiopathic features (MAHA, thrombocytopenia)
• Mortality ~30-50% despite treatment

Red Flags

• Young stroke with no conventional risk factors → screen for APS
• Recurrent pregnancy loss → test antiphospholipid antibodies
• Multiorgan thrombosis → CAPS → emergency treatment

Antiphospholipid Antibody Testing

• Lupus anticoagulant: DRVVT-based assay; strongest predictor of thrombosis
• Anticardiolipin antibodies (IgG/IgM): ELISA; medium-high titre significant
• Anti-β2-glycoprotein I (IgG/IgM): ELISA
• Must be positive on ≥2 occasions ≥12 weeks apart to confirm persistence

Other Bloods

• APTT: may be prolonged (LA effect); does NOT correct with mixing study (inhibitor pattern)
• FBC: thrombocytopenia (50-100 × 10⁹/L)
• Blood film: schistocytes if CAPS
• Direct Coombs test: positive in some (associated AIHA)
• Complement C3/C4: may be low if SLE-associated
• ANA, dsDNA: SLE screening

Imaging

• Guided by clinical presentation: CT head (stroke), CTPA (PE), Doppler USS (DVT)
• Echocardiogram: Libman-Sacks vegetations
• MRI brain: cerebral infarcts, white matter lesions

Thrombotic APS

• Lifelong warfarin: target INR 2-3 (first venous event); some advocate INR 3-4 for arterial events or recurrence on INR 2-3
• DOACs (rivaroxaban, apixaban): NOT recommended for triple-positive APS (TRAPS trial: increased thrombosis vs warfarin)
• DOACs may be acceptable for single/double positive venous APS (controversial; warfarin remains standard)

Obstetric APS

• Aspirin 75-150mg daily (from pre-conception) + LMWH (enoxaparin 40mg SC OD from positive pregnancy test)
• Continue LMWH throughout pregnancy + 6 weeks postpartum
• High-risk: add hydroxychloroquine (reduces complement activation)
• Refractory obstetric APS: consider IVIg, prednisolone, or higher-dose LMWH

Primary Prevention (Asymptomatic aPL Positive)

• Low-dose aspirin 75mg: for persistently positive aPL without prior thrombosis (particularly in SLE)
• Hydroxychloroquine: in SLE patients with aPL (reduces thrombotic risk)

Catastrophic APS

• Anticoagulation (heparin) + IV methylprednisolone + plasma exchange + IVIg
• Rituximab/eculizumab: for refractory CAPS

Referral Criteria

• Confirmed APS → haematology/rheumatology
• Obstetric APS → obstetric medicine/high-risk obstetrics
• CAPS → ITU, multidisciplinary

• Recurrent thrombosis without treatment: 30-50% within 5 years
• Warfarin reduces recurrence to <5% per year
• Triple-positive APS: highest risk; recurrence rate 10-15%/year even on treatment
• Obstetric APS: with aspirin + LMWH, live birth rate 70-80% (vs <20% without treatment)
• CAPS: mortality 30-50% despite treatment
• Overall mortality: primarily from thrombotic events and complications of anticoagulation

Sydney Classification Criteria (2006)

Requires ≥1 clinical + ≥1 laboratory criterion:

Clinical:

1. Vascular thrombosis (arterial, venous, or small vessel)
2. Pregnancy morbidity (as defined above)

Laboratory (positive on ≥2 occasions ≥12 weeks apart):

1. Lupus anticoagulant
2. Anticardiolipin IgG/IgM (medium-high titre)
3. Anti-β2-glycoprotein I IgG/IgM

Risk Stratification