Thrombotic Thrombocytopenic Purpura

Question 1

What is thrombotic thrombocytopenic purpura?

Answer 1

Rare form of microangiopathy characterised by microangiopathic haemolysis, thrombocytopenia and neurological abnormalities.

Question 2

Aetiology of TTP?

Answer 2

Due to deficiency of metalloproteinase ADAMTS13
* Can be hereditary congenital mutation or due to autoimmune inhibition.

Associated with triggers such as medication, AIDS and malignancy.

Question 3

What is the clinical presentation for TTP?

Answer 3

Classic pentad:

• Fever
• Macroangiopathic haemolytic anaemia (MAHA)
• Thrombocytopenic purpura
• CNS involvement: headache, confusion, seizures
• AKI (acute kidney injury)

Question 4

Blood test investigations for TTP?

Answer 4

FBC: normocytic anaemia (secondary to haemolysis), thrombocytopenia and possibly a raised neutrophil count.

U and E: raised urea and creatinine.

Blood film: schistocytes (consistent with haemolysis), elevated reticulocyte count.

Other bloods: LFT, LDH, D-dimer, indirect bilirubin elevated, haptoglobins low.

Question 5

Management of TTP?

Answer 5

Fresh frozen plasma - contains vWF-cleaving protease and complement components.

Plasma exchange - removes antibodies and toxins associated with pathogenesis of disease.

High-dose steroids, low dose aspirin and rituximab can also be given.

Splenectomy may be used to treat patients who do not responds to plasma exchange or who relapse chronically.

Question 6

What is ADAMTS13?

Answer 6

ADAMTS13, also known as von Willebrand factor-cleaving protease (VWFCP), is a zinc-containing metalloprotease enzyme that plays a crucial role in blood clotting.

ADAMTS13 primarily targets von Willebrand factor (vWf), a large protein involved in blood clotting therefore preventing excess blood clotting.

Question 7

What is diagnostic of TTP?

Answer 7

Low ADAMTS13 activity