Question 11

College answer

This question was poorly answered, and a lot of this was due to the nuance and context of the question. Most candidates answered the question with reference to APS or the presence of AP antibodies, and not CAPS, which is a severe manifestation of antiphospholipid syndrome that involves accelerated and widespread thrombosis, which may lead to multi-organ failure. CAPS appears to involve a vicious spiral of progressive complement activation, leading to microvascular thrombosis and tissue damage. There was a poor understanding of the pathophysiology in the answers, and many candidates gave answers pertaining to the diagnosis of the organ damage caused by CAPS, rather than the diagnosis of the syndrome itself.

Discussion

• Pathophysiology
  • In lupus, antiphospholipid autoantibodies are produced which bind to negatively charged phospholipid surfaces normally involved in platelet aggregation (thus impeding clotting and increasing the APTT)
  • Some of these antibodies also bind to open β2 -glycoprotein on endothelial cells
  • This activates compliment, activates inflammatory cells, and promotes coagulation
  • The net result is anticoagulation (because platelet aggregation is impaired) as well as thrombosis (because endothelial function is impaired).
  • Catastrophic APS is the accelerated and systemic version of this process 
• Clinical features
  • ​​​​​​​DVT
  • PE
  • Miscarriage
  • Arterial thrombosis
  • Renal failure
  • Pulmonary disease, largely consisting of PE and ARDS 
  • CNS disease, including venous infarcts, seizures and encephalopathy
  • Skin complications, eg. skin necrosis 
  • Cardiac disease (51% valvular, 25% ischaemic coronary)
  • Thrombocytopenia (in 46%) and coagulopathy (15% have features of DIC)
  • Features of haemolysis (30%)
  • Elevated APTT which does not correct with mixing studies
• Diagnostic features
  • Evidence of involvement from three or more organ systems 
  • Manifestations developing within the same week
  • Histopathological evidence of small vessel occlusion
  • Laboratory confirmation of antiphospholipid syndrome (eg. lupus anticoagulant)
  • "Definite" CAPS satisfies all 4 criteria,  and  "probable" CAPS satisfies criteria 1, 2 and 4.
• Management options
  • ​​​​​​​First line:
    • ​​​​​​​Heparin (but sing anti-Xa to monitor heparinisation)
    • Pulsed methylprednisolone (1g daily for three days)
  • Second line:
    • ​​​​​​​Plasma exchange
    • IV immunoglobulin (0.4g/kg for 5 days)
  • Third line:
    • Cyclophosphamide
    • Rituximab
    • IV prostacycline
    • Defibrotide
    • Ancrod