TTP is an ultra rare, life threatening, thrombotic micro-angiopathy manifested by microvascular occlusions and consequent thrombocytopenia, hemolytic anemia, and organ ischemia. It is an ultra-rare disease with a reported annual occurrence of 1.2 to 11 cases per million and mainly affects otherwise young and healthy adults aged 40 years on average.1,2
“Under the category of thrombotic microangiopathies, a large percentage of those are acquired TTP.”
TTP is caused by severely decreased activity of ADAMTS13, the von Willebrand factor-cleaving protease. Decreased ADAMTS13 activity leads to an accumulation of ULvWF multimers which bind to platelets and induce aggregation.
The consumption of platelets into these microthrombi causes severe thrombocytopenia, tissue ischemia and organ dysfunction, commonly involving the brain, heart, and kidneys, and potentially resulting in acute thromboembolic events such as stroke, myocardial infarction, and venous thrombosis, and in early death.
“[ADAMTS13] is released in a constant way and maintains hemostasis with vWF and ensures that the levels don’t become too high.”
The tissue and organ damage resulting from the ischemia leads to increased levels of lactate dehydrogenase (LDH; nonspecific, as this is also a marker for hemolysis), troponins (heart), and creatinine (kidney). Acquired TTP, caused by autoantibody inhibition of ADAMTS13 activity, is the most common form of the condition. Congenital TTP, caused by mutations in the ADAMTS13 gene, is very rare. Episodes of aTTP have been reported to be associated with an acute mortality of up to 20%.3,4 Most deaths occur within 30 days of diagnosis,5-7 and a median time to death of 9 days.7
“Von Willebrand factor is the largest protein in the body, or one of the largest...”
Refractoriness to therapy (defined as a lack of improvement of the thrombocytopenia after 4–7 days of standard treatment and persistent elevated LDH levels, or as a failure of platelet count doubling after 4 days of standard therapy together with elevated LDH levels) has been identified as an indicator of a poor prognosis for survival. The incidence of refractoriness is approximately 17% and is associated with a mortality rate reported to be as high as 42%.3,8
In addition to the acute risks of the disease, patients experiencing an episode of aTTP may suffer long-term consequences such as cognitive deficits, depression, and arterial hypertension,9 and are at risk for recurrence. The reported recurrence rate ranges from 10-84%.10 Recurrences typically occur within 1-2 years11 but have been reported up to 30 years after the initial episode.10,12
“The formation of blood clots in small blood vessels throughout the body... results in organ disfunction, commonly involving the brain, heart, and kidneys...”