QuestionSBA
QuestionChoice
This patient has thrombotic thrombocytopenic purpura (TTP), presenting with the classic pentad of symptoms: acute kidney injury, neurological features, microangiopathic haemolytic anaemia, low platelets, and fever. It is usually an acquired disorder of ADAMTS13, where neutralising antibodies against this metalloprotease results in accummulation of high molecular weight multimeters of Von Willebrand Factor, which are highly active. ADAMTS13 usually cleaves these HMW multimers. This leads to excess platelet activation and clumping, leading to microangiopathic haemolytic anaemia. The clotting cascade is not activated, and so clotting factors are not consumed, resulting in a normal PT, APTT, fibrinogen, and d-dimers. Definitive treatment is plasma exchange to remove circulating antibodies.
53227
a
Plasma exchange
QuestionChoice
Rituximab an anti-CD20 monoclonal antibody that depletes B cells, which produce antibodies that neutralise the ADAMTS13 protein. It may be considered in the management of TTP resistant to plasma exchange.
53231
e
Rituximab
QuestionChoice
This is a monoclonal antibody that inhibits Von Willebrand Factor, and may be considered in the management of TTP resistant to plasma exchange.
53230
d
Caplacizumab
QuestionChoice
Splenectomy may be considered in the management of TTP resistant to medical management.  The spleen is responsible for making antibodies which block the ADAMTS13 protein. Removing the spleen means that antibodies are no longer made against the ADAMTS13 protein.
53229
c
Splenectomy
QuestionChoice
Steroids may be considered in the management of TTP resistant to plasma exchange.
53228
b
Steroids
QuestionComment
Why does it say definitive treatment then give first line as correct answer? 
18640
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Jaundice Dermis
QuestionComment
would splenectomy not be the definitive treatment?
26495
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Retrograde Sclerosis
QuestionComment
why not ITP?

43643
QuestionComment
I think the suddenness of the onset is more characteristic of TTP than ITP
60344
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Dr Bob Kelso
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Zygomatic Gland
Concept
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# Summary

Thrombotic Thrombocytopenic Purpura (TTP) is a disorder caused by abnormally cleaved von-Willebrand factor due to abnormal ADAMST13 activity, which leads to platelet aggregation, thrombus formation and systemic microangiopathy. Key signs and symptoms include fever, Microangiopathic haemolytic anaemia (MAHA), Thrombocytopenic purpura, CNS involvement and Acute Kidney Injury. Investigation through urine dipstick, FBC, U&E, clotting tests, blood film, LFT, LDH, D-dimer, and haptoglobin levels are crucial. Low ADAMST13 activity is diagnostic. Management strategies include steroids and plasma exchange.

# Definition

Thrombotic Thrombocytopenic Purpura (TTP) is a disorder caused by abnormally cleaved von-Willebrand factor due to abnormal ADAMST13 activity. This condition leads to platelet aggregation, thrombus formation and systemic microangiopathy.


# Causes

- Hereditary: Congenital mutation of ADAMST13
- Auto-immune: AI inhibition of ADAMST13


# Clinical Features

The **pentad** to remember:

- Fever
- Microangiopathic haemolytic anaemia (MAHA)
- Thrombocytopaenic purpura
- CNS involvement: headache, confusion, seizures
- AKI

# Investigations

- Urine dipstick may show haematuria and non-nephrotic range proteinuria
- FBC shows a normocytic anaemia (secondary to haemolysis), thrombocytopenia, and possibly a raised neutrophil count
- U&E shows a raised urea and creatinine
- Clotting is typically normal
- The blood film will reveal reticulocytes (secondary to haemolysis) and schistocytes (fragmented red cells)
- LFT, LDH, D-dimer will be raised and haptopglobins will be low consistent with haemolysis
- **Low ADAMST13 activity is diagnostic**

# Management

- Fresh frozen plasma (**FFP**) – contains vWF-cleaving protease and complement components 
- **Plasma exchange** – removes antibodies and toxins associated with the pathogenesis of the disease
- High-dose steroids, low-dose aspirin and rituximab can also be given 


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Thrombotic thrombocytopenic purpura (TTP)
Topic
8
Haematology
Condition
30
Anaemia
UkmlaTopic
6
Clinical haematology
10706
Thrombotic thrombocytopenic purpura (TTP) is a life-threatening blood disorder treated primarily with plasma exchange, which removes harmful substances and restores functional ADAMTS13
Presentation
469
Purpura
UkmlaTopic
6
Clinical haematology
A 32-year-old female presents to A&E following a seizure. She is post-ictal and unable to give a history. On examination, she has a low grade fever and has multiple purpura across her body. There is no evidence of meningism. Her blood tests show the following: 

||||
|--------------|:-------:|---------------|
|Haemoglobin|54 g/L|(M) 130 - 170, (F) 115 - 155|
|Platelets|22x10<sup>9</sup>/L|150 - 400|

Her creatinine is raised, but no baseline is available. A blood film reveals schistocytes. Her PT, APTT, fibrinogen, and d-dimers are within normal range.


What is is the definitive treatment for this presentation?
a