Antiphospholipid Syndrome (APS)

Presentation

• Acquired thrombophilia → increased risk of arterial and venous thrombi

• Recurrent miscarriages, pre-eclampsia, fetal growth restriction, MI, CVA

• Associated with SLE and autoimmune disorders, also seen in Sjögren’s syndrome, RA, systemic sclerosis

• May present with livedo reticularis, thrombocytopenia, or cardiac valve disease (valve thickening and regurgitation)

• Catastrophic APS (CAPS) is a rare, life-threatening variant causing multi-organ failure due to microvascular thrombosis

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Pathophysiology

• Antiphospholipid antibodies (aPL) interact with inflammatory endothelial factors → disrupt coagulation → clot formation

• Triple positivity (lupus anticoagulant, anticardiolipin, beta-2 glycoprotein 1) confers highest risk of recurrent thrombosis

• aPL antibodies may be additive to traditional risk factors (smoking, hypertension, hyperlipidaemia)

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Investigations

• Antibody tests:

  • Lupus anticoagulant

  • Anticardiolipin antibody

  • Beta-2 glycoprotein 1 antibody

• Other tests:

  • FBC (thrombocytopenia, anaemia)

  • Coagulation studies (aPTT prolongation, INR monitoring)

• Repeat aPL testing at least 12 weeks apart to confirm persistent positivity

• Assess modifiable risk factors (smoking, hypertension, dyslipidaemia) to reduce vascular risk

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Diagnosis

• Requires one clinical manifestation (thrombotic or obstetric) plus persistent aPL antibodies (two positive tests, 12 weeks apart)

• Higher-risk profiles: Triple positivity and history of severe thrombotic or obstetric complications

• Catastrophic APS diagnosed when thrombosis affects ≥3 organs in <1 week

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Treatment

• Thrombotic APS:

  • Lifelong warfarin (target INR 2.5–3.5)

  • Avoid NOACs (less effective in APS, increased risk of recurrent thrombosis)

  • Recurrent events: Warfarin + antiplatelet therapy (aspirin/dipyridamole)

  • Consider hydroxychloroquine for added protection in high-risk patients

  • Statins may be considered in high-risk patients with atherosclerotic risk factors

  • Specialist input for refractory cases, catastrophic APS

• Obstetric APS:

  • Low-dose aspirin + LMWH during pregnancy and for 6–12 weeks postpartum

  • High-risk cases: Add hydroxychloroquine or IVIG (specialist decision)

  • Warfarin contraindicated in pregnancy → switch to therapeutic LMWH

  • Postpartum remains high risk for thrombosis; extended prophylaxis advised

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Obstetric vs Thrombotic APS

Clinical Manifestations

Obstetric APS

• ≥3 early miscarriages (<10 weeks)

• ≥1 fetal death (>10 weeks)

• Preterm birth (<34 weeks) due to pre-eclampsia/placental insufficiency

Thrombotic APS

• DVT/PE (most common initial presentation)

• Stroke/TIA in young patients

• Other: Myocardial infarction, retinal occlusion, microvascular thrombosis

Management

Obstetric APS

• Low-dose aspirin + LMWH during pregnancy and 6–12 weeks postpartum

• High-risk cases: Add hydroxychloroquine or IVIG (specialist decision)

• Postpartum period remains high risk for thrombosis; prophylaxis continuation advised

Thrombotic APS

• Lifelong anticoagulation with warfarin

• Recurrent events: Combine warfarin with antiplatelet therapy (aspirin/dipyridamole)

Catastrophic APS (CAPS)

• Acute multi-organ failure due to widespread microvascular thrombosis

• Precipitated by infection, surgery, malignancy, anticoagulation withdrawal

• Requires urgent hospitalisation, anticoagulation, high-dose steroids, IVIG, and plasma exchange

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Key Considerations

• Screening for aPL antibodies only in specific clinical contexts (young stroke, unprovoked VTE, recurrent pregnancy loss)

• Asymptomatic aPL positivity does not warrant routine anticoagulation, but may justify aspirin in high-risk individuals

• Hydroxychloroquine recommended for SLE patients with aPL antibodies

• Regular INR monitoring crucial, especially in high-risk (triple-positive) patients

• Avoid oestrogen-containing contraceptives and HRT in APS due to increased thrombotic risk