TTP and aHUS

Question 1

Pathophysiology of TTP

Answer 1

ADAMSTS-13 cleaves vWF –> inactivation of vWF –> No thrombosis

TTP = Deficient ADAMTS-13 or ADAMTS-13 antibody –> can’t cleave vWF –> thrombosis

Question 2

Presentation and Diagnosis of TTP

Answer 2

Anaemia
Thrombocytopenia
Neurological dysfunction - altered LOC, seizures, hemiplegia, paresthesia, visual disturbance, aphasia
Fever
Haemoglobinuria

Diagnosis:

• Thrombocytopenia
• Evidence of haemolysis - Raised LDH, Schistocytes, low haptoglobin, coombs positive
• ADAMSTS13 < 5%

Question 3

Treatment of TTP

Answer 3

Plasma exchange

Rituximab

Question 4

HUS

Answer 4

Shiga toxin from E. Coli gastrointestinal infection causes endothelial injury –> thrombotic microangiopathy

History of diarrheal illness
Haemolysis picture
Shiga toxin positive

Self limiting illness = supportive care

Question 5

aHUS pathophysiology

Answer 5

Chronic uncontrolled activation of complement
Through either:
- Gain of function mutations in C3 or Complement Factor B or
- Loss of function in complement regulators - Complement factor H, thrombomodulin, CFI or MCF

Results in thrombosis and haemolysis

Question 6

aHUS presentation and diagnosis

Answer 6

Thrombocytopenia and evidence of haemolysis 
AND
Evidence of organ damage:
- Renal dysfunction - 80%
- Neurological 
- GIT
- Cardiac

Exclude TTP and HUS - ADAMSTS13>5% and negatvie shiga toxin

Question 7

Treatment for aHUS

Answer 7

Eculizumab

Humanized monoclonal Ab to C5

• -> prevents cleave of C5 into C5a and C5b
• -> Stops activation of terminal complement factors

Must be vaccinated against neisseria prior to commencement