Thrombotic thrombocytopenic purpura is an uncommon syndrome characterised by:
- fever
- microangiopathic haemolytic anaemia
- thrombocytopenia
- neurologic and renal abnormalities
Thrombotic thrombocytopenic purpura (TTP), a potentially fatal clinical syndrome, is primarily caused by autoantibodies against the von Willebrand factor (VWF)-cleaving metalloprotease ADAMTS13 (2)
- in general, severe deficiency of plasma ADAMTS13 activity (<10 IU/dL) with or without detectable inhibitory autoantibodies against ADAMTS13 supports the diagnosis of TTP if a patient presents with thrombocytopenia and microangiopathic hemolytic anemia (i.e. schistocytes, elevated serum lactate dehydrogenase, decreased hemoglobin and haptoglobin) without other known etiologies that cause thrombotic microangiopathy (TMA)
TTP often follows infection or in women, oral contraception or pregnancy
TTP is a critical medical condition requiring immediate transfer for treatment. (1)
- 50% of patients require intensive care admission and without treatment, the mortality in acute TTP is >90%.
TTP results from a deficiency of the enzyme ADAMTS 13, required for Von Willebrand factor (vWF) cleavage
- severely reduced enzyme levels are caused either by a genetic abnormality or through their destruction by antibodies
- deficiency of the ADAMTS13 enzyme results in insufficient processing of the large vWF clotting factor which unravels during passage through the microcirculation leading to platelet aggregation and multi-organ microvascular thrombosis involving neurological, cardiac, gastro-intestinal and renal disease
- occlusion of small vessels also causes a fragmentation haemolysis (microangiopathic haemolytic anaemia) and platelet consumption resulting in thrombocytopenia.
Young adults from 20 to 50 years are predominantly affected, with a slight female preponderance
Prompt differentiation of TTP from other causes of TMA is crucial for the initiation of an appropriate therapy to reduce morbidity and mortality.
Management
- plasma infusion is often sufficient for prophylaxis or treatment of hereditary TTP due to ADAMTS13 mutations
- daily therapeutic plasma exchange is the initial treatment of choice for acquired TTP with autoantibodies
- immunomodulatory therapies, including corticosteroids, rituximab, vincristine, cyclosporine, cyclophosphamide, and splenectomy, etc. should be considered to eliminate autoantibodies for sustained remission (2)
Notes
- normal to moderately reduced plasma ADAMTS13 activity (>20 IU/dL) in a similar clinical context supports an alternative diagnosis such as atypical hemolytic uremic syndrome (aHUS) or other types of TMA
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