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| As indicated above, there
are two different forms of TTP: congenital and acquired. |
| Congenital
TTP is caused by
mutations in the ADAMTS13 gene, which
is located on chromosome 9q34. It is inherited as
an autosomal recessive disorder
and it is often, but not exclusively, manifested at
birth or during childhood (17,21,22).
The congenital cases are extremely
rare (incidence 1: 1.000.000) and represent
a small percentage (5%) of the cases of TTP. Up to
now more than 60 mutations have been identified: 60%
of them are missense mutations, whereas the remaining
40% are (Table
1) non-sense, frameshift
or splice-site mutations. Even though 75% of missense
mutations are located in first half of the ADAMTS13
gene, no apparent clustering or mutation "hot-spots"
have been identified. |
| Acquired
TTP can basically be distingueshed into two types:
immune-mediated forms, due
to autoantibodies that inhibit the proteolytic
activity of ADAMTS13 and/or
bind the protease to accelerate its clearance
from plasma (23-26),
and those probably secondary
to massive endothelial stimulation
with consequent release of ULVWF multimers in amounts
exceeding the ability of the protease system to degrade
them. |
| Both these pathogenic
situations are usually triggered by physiological
or pathological condition (Table
2) which cause massive endothelial activation
(1,27,30). |
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