Thrombotic thrombocytopenic purpura (TTP) is a potential diagnosis in any patient with haemolytic anaemia and thrombocytopenia - 95% of cases are fatal if left untreated.
Symptoms are usually non-specific, although half of patients have neurological abnormalities. Pentad of fever, renal failure, haemolytic anaemia, thrombocytopenia, and neurological changes are often seen, although most patients do not have the entire pentad.
Examination of the peripheral smear is critical and shows evidence of microangiopathic haemolytic anaemia with fragmented red blood cells (schistocytes) and thrombocytopenia.
An urgent haematological consultation is recommended for suspected cases.
Plasma-exchange therapy combined with corticosteroids is the mainstay of treatment for acute acquired (idiopathic) TTP. Caplacizumab may be prescribed as an adjunctive therapy in adults.
Renal and neurological dysfunctions are the main complications.
TTP is a clinical syndrome characterised by microangiopathic haemolytic anaemia and thrombocytopenic purpura. Although the original descriptions included a pentad of microangiopathic haemolytic anaemia, thrombocytopenic purpura, neurological dysfunction, renal dysfunction, and fever, most patients do not have the entire pentad. There are no pathognomic features of TTP. Without treatment, TTP is typically fatal. Pathophysiology involves the absence of von Willebrand factor cleaving enzyme (ADAMTS-13), resulting in unusually large von Willebrand multimers that lead to platelet aggregation and subsequent thrombocytopenia and microthrombi. Some evidence suggests that at least 33% of patients with idiopathic TTP may have severe ADAMTS-13 deficiency. For the diagnosis of TTP, ADAMTS-13 activity levels of <5% to 10% are diagnostic.
The British Committee for Standards in Haematology has proposed the following subgroups of TTP:
Acute idiopathic TTP (the most common type of TTP, and the focus of this topic)
Haemolytic uraemic syndrome is a similar syndrome but usually has a more pronounced renal component and is caused by Shiga toxin produced by certain E coli infections. Atypical haemolytic uraemic syndrome (aHUS) is a complement-mediated microangiopathy which clinically may masquerade as TTP, but is due to abnormalities in complement regulation. See the BMJ Best Practice topic: 'Haemolytic uraemic syndrome' for more information on aHUS.
History and exam
Key diagnostic factors
- non-specific prodrome
- severe neurological symptoms (coma, focal abnormalities, seizures)
- mild neurological symptoms (headache, confusion)
Other diagnostic factors
- age 30 to 50 years
- digestive symptoms (nausea, vomiting, diarrhoea, abdominal pain)
- bleeding symptoms (purpura, ecchymosis, menorrhagia)
- black ethnicity
- female gender
- pregnancy (near term or post-partum period)
- cancer therapies
- HIV infection
- bone marrow transplantation
- antiplatelet agents
1st investigations to order
- platelet count
- peripheral smear
- reticulocyte count
- urea and creatinine
- direct Coombs' test
Investigations to consider
- ADAMTS-13 activity assay and inhibitor titres
acquired (idiopathic) TTP: acute episode
acquired (idiopathic) TTP: following resolution of acute episode
Sandeep K. Rajan, MD
Associate Professor of Medicine
Division of Hematology and Medical Oncology
SKR has received honoraria for advisory consultancy and speakers bureau, and received research funds from Alexion, Novo-Nordisk, Sanofi and Appelis.
Dr Sandeep K. Rajan would like to gratefully acknowledge Dr Rebecca Fischer Connor, a previous contributor to this topic.
RFC declares that she has no competing interests.
James N. George, MD
George Lynn Cross Professor
Department of Biostatistics and Epidemiology
University of Oklahoma Health Sciences Center
JNG declares that he has no competing interests.
Christoph Pechlaner, MD
Associate Professor of Medicine
Department of Internal Medicine
Innsbruck Medical University
CP declares that he has no competing interests.
- Haemolytic uraemic syndrome (HUS)
- Atypical haemolytic uraemic syndrome (aHUS)
- Hypertension, malignant
- ISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpura
- Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies
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