Welcome to this lecture on Thrombotic Thrombocytopenic Purpura, or TTP.
Although TTP is a relatively rare disorder,
we know a great deal about it and the differential diagnosis is vast.
So I will have to be selective and will emphasize the following topics.
First, I will discuss the diagnosis, treatment,
and prognosis of TTP using a historical approach.
Then, I will summarize recent discoveries about the pathophysiology of TTP,
focusing on the role of the ADAMTS13 metallic protease.
And I will discuss recent clinical studies of
ADAMTS13 in familial and autoimmune idiopathic TTP.
At the end, briefly,
I will look at the frontier of clinical research on
TTP and consider what we may learn during the next few years.
In its most classic form,
TTP is characterized by a pentad of signs that includes: severe
microangiopathic hemolytic anemia with
abundant fragmented red cells called schistocytes
as indicated by the arrows in this blood film,
thrombocytopenia, the neurological signs and symptoms that may fluctuate rapidly,
renal disease with proteinuria, hematuria,
casts and renal insufficiency, and fever.
Microangiopathic hemolytic anemia and thrombocytopenia are
almost always present although the remaining features of the pentad are quite variable.
The annual incidence of TTP is
about four to five per million and most patients are women in their 30s or 40s.
If untreated, almost all patients die within a few weeks of diagnosis.
Fortunately, treatment with plasma exchange has
reduced the mortality to less than 20 percent.
Thanks to discoveries of the last decade,
we now have a good idea why plasma exchange works.