Thrombotic Thrombocytopenic Purpura (TTP)

Question 1

what is thrombotic thrombocytopenic purpura (TTP)?

Answer 1

a form of thrombotic microangiopathy (TMA) caused by severe ADAMTS13 deficiency, which can be immune-mediated or hereditary

Question 2

what is the pathophysiology of TTP?

Answer 2

• involves nonimmunologic platelet destruction
• endothelial damage is common
• loose strands of platelets and fibrin are deposited in multiple small vessels and damage passing platelets and RBCs, causing significant thrombocytopenia and anaemia
• platelets are also consumed within multiple small thrombi, contributing to the thrombocytopenia

Question 3

what organs may be involved in thrombotic microangiopathy of TTP?

Answer 3

involves platelet–von willebrand factor (VWF) thrombi at arteriocapillary junctions, primarily affecting the:
- brain
- gastrointestinal tract
- kidneys

Question 4

what is the cause of TTP?

Answer 4

congenital or acquired deficient activity of the plasma enzyme ADAMTS13

Question 5

what are the symptoms of TTP?

Answer 5

• initial symptoms may be mild and develop gradually or acute and severe
• fatigue (e.g. anaemia)
• purpura (e.g. thrombocytopenia)
• bleeding
• manifestations of ischaemia (e.g. weakness, confusion, seizures, coma, abdominal pain, nausea, vomiting, diarrhoea, arrhythmia)

Question 5

what is the function of the plasma enzyme ADAMTS13?

Answer 5

a plasma protease that cleaves von willebrand factor (VWF) into smaller sizes and thereby eliminates unusually large VWF multimers that would otherwise accumulate on endothelial cells where they can cause platelet thrombi

Question 6

what are the investigations for TTP?

Answer 6

• FBC
• blood film
• reticulocyte count
• DAT
• serum LDH
• PT
• haptoglobin
• serum bilirubin
• urinalysis
• U&Es
• ADAMTS13

Question 7

what is the diagnosis of TTP suggested by?

Answer 7

• thrombocytopenia
• anaemia
• fragmented RBCs (e.g. schistocytes)
• haemolysis (e.g. ↓ Hb, ↓ haptoglobin, ↑ LDH, ↑ reticulocyte count, ↑ bilirubin)
• negative DAT

Question 8

what laboratory finding is characteristic of TTP?

Answer 8

ADAMTS13 levels < 10% with the presence of antibodies against ADAMTS13 is characteristic of most adults with TTP

Question 9

what is the management of TTP?

Answer 9

• plasma exchange
• corticosteroids
• rituximab
• ? caplacizumab