Thrombotic thrombocytopenic purpura (TTP), also known as Moschcowitz syndrome, is a rare but life-threatening condition characterized by thrombocytopenia, microangiopathic hemolytic anemia (MAHA) and end-organ damage.
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Epidemiology
The prevalence of thrombotic thrombocytopenic purpura is 1 in 100,000 2. 90% of cases occur in adulthood and only 10% occur in childhood 3. The condition is twice as common in women than in men 2.
Clinical presentation
Originally a pentad of signs and symptoms was said to be present in thrombotic thrombocytopenic purpura:
neurological symptoms (e.g. weakness, headache, coma)
renal insufficiency
microangiopathic hemolytic anemia
thrombocytopenia
However, it has been shown that all five are present in less than 10% of cases 2. In reality, a combination of any of the above should raise the possibility of thrombotic thrombocytopenic purpura.
Purpura (widespread bruising) is usually present. Abdominal pain and chest pain from intestinal and cardiac ischemia are also common 3.
Pathology
Etiology
Normally a protease known as ADAMTS13 (a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13) is responsible for cleaving von Willebrand multimers and preventing the aggregation of von Willebrand factor and subsequent platelet activation and hyperadhesion.
Thrombotic thrombocytopenic purpura is caused by an acquired or congenital deficiency in ADAMTS13 activity which produces inappropriate platelet clumping leading to thrombocytopenia. Destruction of red blood cells by these platelet clumps produces hemolytic anemia and embolization of these aggregates produces embolic events 2-4.
90% of cases are acquired with autoimmune inactivation of the protease by IgG autoantibodies. Antibodies are detectable in about 75% of acute cases 3. Approximately half of all thrombotic thrombocytopenic purpura patients do not have a clear inciting condition or offending drug; this is known as idiopathic thrombotic thrombocytopenic purpura. However, in the other half, underlying disease (e.g. SLE, HIV, cancer), pregnancy, organ transplantation or drugs (e.g. clopidogrel, cyclosporine A) may cause acquired autoantibodies 3. In roughly 2% of cases, congenital deficiency of ADAMTS13 is the cause of thrombotic thrombocytopenic purpura 3.
Markers
The activity of the ADAMTS13 enzyme may be measured and is specific for thrombotic thrombocytopenic purpura and levels are reduced to under 10% of normal in thrombotic thrombocytopenic purpura 4.
Radiographic features
CT
Approximately a quarter of patients have changes on brain CT with posterior reversible encephalopathy syndrome (PRES) being present in half of these cases 1.
MRI
One study using MRI showed that 82% of patients with thrombotic thrombocytopenic purpura had acute findings. Posterior reversible encephalopathy syndrome (PRES) was present in half of these patients. Acute cerebral ischemia and hemorrhage are uncommon findings. After treatment, in the majority of cases, the imaging findings resolve 1.
Treatment and prognosis
Plasma exchange is the first-line treatment for thrombotic thrombocytopenic purpura 2.
History and etymology
Thrombotic thrombocytopenic purpura was first described in 1924 by the American physician Eli Moschcowitz (1879-1964) in a 16-year-old girl. Hence, its historic eponym, Moschcowitz syndrome 3.
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