Antiphospholipid Syndrome

Autoimmune disease characterised persistent antibodies to circulating anti-phospholipid, causing a pro-coagulant state that may present as:

• Thrombotic APS
  Venous, arterial, or microvascular thrombosis.
  • VTE
• Catastrophic APS
  Multi-organ (⩾3) thrombosis within 7 days, often with:
  • ARDS
  • Diffuse alveolar haemorrhage
  • Encephalopathy
  • Adrenal haemorrhage
  • AKI
• Obstetric APS
  
  • Foetal loss after 10^th week of gestation
  • Recurrent early miscarriages
  • IUGR
  • Pre-eclampsia with severe features
• Non-thrombotic APS
  
  • Valvular heart disease
  • Nephropathy
  • Haemolytic anaemia with thrombocytopaenia
  • Cognitive dysfunction

CAPS can be clinically indistinguishable from other thrombotic microangiopathies (covered under Thrombotic Microangiopathies); persistent antiphospholipid antibodies are required to confirm the diagnosis.

Epidemiology and Risk Factors

Associations:

• Systemic autoimmune disease
  • SLE

Pathophysiology

• β₂-glycoprotein I is a circulating plasma protein that binds to phospholipid surfaces
• Antiphospholipid antibody binds to β₂-glycoprotein on endothelial cells
  These include:
  • Anticardiolipin antibody
  • Lupus anticoagulant
  • Anti-β₂-glycoprotein antibody
• The antibody-glycoprotein complex induces a procoagulant state by:
  • Up-regulating prothrombotic cellular adhesion molecules
    • E-selectin
    • Tissue factor
  • Suppressing tissue factor pathway inhibitor

Aetiology

Clinical Features

Thromboses:

• Venous thrombosis
  • DVT
  • PE
  • Cerebral venous sinus
• Arterial thrombosis
  • MI
  • Thrombotic valvular disease
  • Stroke
  • Mesenteric ischaemia
  • Skin necrosis
• Miscarriage

Assessment

History:

• Autoimmune disease history

Exam:

• Livedo

Livedo reticularis

Investigations

Bedside:

• TTE
  • Valvular vegetations

Laboratory:

• Blood
  • FBE
    • Thrombocytopaenia
      <20×10⁹/L is rare.
    • Haemolytic anaemia
      May be immune-mediated or non-immune mediated.
  • Blood film
    • Schistocytes
      To distinguish haemolytic anaemia type.
  • Coag
    • Isolated ↑ APTT that does not correct on mixing studies
  • UEC
    • AKI
  • Antiphospholipid antibody

Imaging:

Other:

Diagnostic Approach and DDx

The Sapporo criteria requires both:

These criteria are incomplete for the full spectrum of APS features, and will probably be revised.

• Thrombotic complication
  Including obstetric.
• Persistent antiphospholipid antibodies

Management

• Anticoagulation
  Heparin with anti-Xa targeting.
• Immunosuppression

Resuscitation:

Specific therapy:

• Pharmacological
  • For CAPS:
    • Anticoagulation
      • Heparin preferable
        Monitor with anti-Xa targeting 0.3-0.7.
    • Immunotherapy
      • Corticosteroids
        Methylprednisolone 1g daily for 3 days.
      • IVIG
        • Theoretical benefit
        • 0.4g/kg for 5 days
      • Consider cyclophosphamide or rituximab
• Procedural
  • For CAPS:
    • Plasma exchange
      FFP preferred exchange solution.
• Physical

anti-Xa detects amount of residual unbound Xa, indicating the degree to which the heparin-antithrombin complex has bound Xa.

Supportive care:

Disposition:

Preventative:

• Secondary prevention
  • Aspirin and prophylactic enoxaparin
    • Preferred in pregnancy
  • Therapeutic anticoagulation
    • For VTE or arterial thrombosis
    • Warfarin recommended
      • Target INR 2-3
      • INR target may ↑ to 3-4 if recurrent thromboses
    • Evidence supporting DOAC is unclear
  • Aspirin may be added if:
    • Concurrent coronary artery disease
    • Thrombosis occurs on warfarin

Marginal and Ineffective Therapies

Anaesthetic Considerations

Complications

Prognosis

CAPS:

• 35-50% mortality

Key Studies

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References