Thrombotic thrombocytopenic purpura (TTP) is a potential diagnosis in any patient with hemolytic anemia and thrombocytopenia - 95% of cases are fatal if left untreated.
Symptoms are usually nonspecific, although half of patients have neurologic abnormalities. Pentad of fever, renal failure, hemolytic anemia, thrombocytopenia, and neurologic 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 hemolytic anemia with fragmented red blood cells (schistocytes) and thrombocytopenia.
An urgent hematology 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 neurologic dysfunctions are the main complications.
TTP is a clinical syndrome characterized by microangiopathic hemolytic anemia and thrombocytopenic purpura. Although the original descriptions included a pentad of microangiopathic hemolytic anemia, thrombocytopenic purpura, neurologic 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)
Hemolytic uremic 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 hemolytic uremic 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: “Hemolytic uremic syndrome” for more information on aHUS.
History and exam
Key diagnostic factors
- nonspecific prodrome
- severe neurologic symptoms (coma, focal abnormalities, seizures)
- mild neurologic symptoms (headache, confusion)
Other diagnostic factors
- age 30 to 50 years
- digestive symptoms (nausea, vomiting, diarrhea, abdominal pain)
- bleeding symptoms (purpura, ecchymosis, menorrhagia)
- black ethnicity
- female gender
- pregnancy (near term or postpartum period)
- cancer therapies
- HIV infection
- bone marrow transplantation
- antiplatelet agents
1st investigations to order
- platelet count
- peripheral smear
- reticulocyte count
- BUN and creatinine
- direct Coombs test
Investigations to consider
- ADAMTS-13 activity assay and inhibitor titers
acquired (idiopathic) TTP: acute episode
acquired (idiopathic) TTP: following resolution of acute episode
- Hemolytic uremic syndrome (HUS)
- Atypical hemolytic uremic 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
- Log in or subscribe to access all of BMJ Best Practice
Use of this content is subject to our disclaimer