Question 3

College answer

Not available.

Discussion

Bucking the conventional wisdom that CICM Fellowship Exam questions follow their subject with a lag of 12-18 months, this one brings up a topic of considerable contemporary importance in the latter half of 2021, when the Australian population were working hard on developing herd immunity. For this SAQ from August 2021, the most effective revision resource would have to be the TSANZ statement on VITT from August 2021. 

Pathophysiology and risk factors:

• Risk factors: 
  • AstraZeneca (ChAdOx1 nCov-19) vaccine
  • Johnson & Johnson (Ad26.COV2. S) vaccine
  • Female sex
  • Young age (<55 yo)
• Pathophysiology:
  • Antibodies form to the complex of PF4 platelet surface proteins and adenoviral RNA from the vaccine (a rare failure of self-tolerance)
  • This is similar to HITS, but has a different epitope
  • Antibody (IgG) binding to this epitope results in platelet activation and autoimmune platelet destruction

Clinical presentation:

• History:
  • Vaccine within 4-42 days of the presentation
  • Thrombosis: abdominal pain, decreased level of consciousness, visual changes, seizures, leg pain or swelling
  • Thrombocytopenia: unexplained bleeding
• Examination:
  • Clinical features of DVT or PE
  • Cranial nerve signs supportive of cavernous sinus thrombosis
  • Features of stroke
  • Ascites, features of liver failure
  • Petechii, ecchymoses
• Laboratory data:
  • Thrombocytopenia
  • Elevated D-dimer
  • Evidence of organ dysfunction (eg. deranged LFTs)
  • Positive VITT ELISA immunoassay
  • Positive VITT functional platelet assay
• Imaging
  • Finding of thrombosis (CVT, portal vein, or even arterial)

Three differential diagnoses:

• HIT
• ITP
• TTP/HUS

Supportive and specific management:

• Non-heparin anticoagulation (eg. bivalirudin or fondparinux)
• IV immunoglobulin, 1-2g/kg over 2 days
• Plasmapheresis +/- high dose methylprednisolone if not improving or if thrombosis is severe and extensive