Antiphospholipid syndrome

Question 1

Define antiphospholipid syndrome

Answer 1

Association of antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, and/or anti-beta2-glycoprotein I) with a variety of clinical features characterised by thromboses and pregnancy-related morbidity.

Question 2

Explain aetiology/risk factors

Answer 2

AETIOLOGY

• Antiphospholipid syndrome (APS) can be:
  
  • Primary APS (no underlying autoimmune disease) - associated with HLA-DR7
  • Secondary APS (caused by other conditions - SLE is the most common secondary cause
• Formation of procoagulatory antiphospholipid antibodies (against phospholipid binding proteins)
• Induction of a hypercoagulable state → increased risk of thrombosis and embolism and results in the development of venous, arterial, and microvascular thromboses, and/or pregnancy-associated morbidity.

RISK FACTORS

• SLE
• Other autoimmine conditions (especially AIHA)

Question 3

Summarise the epidemiology of Antiphospholipid syndrome

Answer 3

• Females
• 15-50 (mean age 34)
• White

Question 4

Recognise the presenting symptoms of antiphospholipid syndrome

Answer 4

APS usually manifests with recurring thrombotic events that may affect any organ.

• Recurrent miscarriages and premature births (due to pre-eclampsia, eclampsia or placental insufficiency)
• History of venous thromboses
  
  • DVT
  • PE
  • Venous ulcers
• History of arterial thromboses (less common) – stroke, TIA, MI

Question 5

Signs on physical examination (2)

Answer 5

• Livedo reticularis (mottled/reticular purplish discoloration of the skin due to pro-thrombotic state in cutaneous vasculature)
• Heart murmur due Libman-Sacks endocarditis (fibrin vegetations on valves)
• Signs of SLE

Question 6

Identify appropriate investigations for antiphospholipid syndrome and interpret the results

Answer 6

• FBC showing thrombocytopenia
• Serology for APL Antibodies:
  
  • Lupus anticoagulant
    
    • If Lupus anticoagulant is +ve then aprolonged aPTT
    • Mixing study: The patient’s plasma is mixed with normal plasma. If the prolonged aPTT is caused by a lack of clotting factors, the factors contained in the normal plasma will normalize the aPTT. In the presence of lupus anticoagulants, the aPTT will remain unchanged.
  • Anticardiolipin
  • Anti-β2 Glycoprotein 1

Question 7

Diagnostic criteria for APS

Answer 7

Diagnostic criteria:

• At least 1 vascular thrombotic event (arterial, venous, or small-vessel in any tissue or organ) or pregnancy morbidity with the presence of antiphospholipid antibodies on 2 or more occasions, that are at least 12 weeks apart.
  
  • E.g. one or more episodes of DVT/miscarriage then 3 months later one or more epsiodes of ulcer/miscarriage and both times there was a high APL antibody titre

Question 8

Management

Answer 8

primary thromboprophylaxis

• low-dose aspirin 75mg daily

secondary thromboprophylaxis

• lifelong warfarin with a target INR of 2-3
• if recurrent events then target is 3-4