The therapeutic strategies used in the
management of TTP involve the use of plasma infusion and/or
plasma exchange. These treatments reduced mortality from about
80-90% to 20-25%. The description of the key role of ULVWF
multimers in the pathogenesis of TTP and the subsequent identification
of ADAMTS13 clarified the mechanism leading to the therapeutic
efficacy of plasma treatment: this procedure removes the anti-ADAMTS13
autoantibodies in the immunomediated forms and replaces the
lack of the protease in the congenital forms. It has been
demonstrated that a delay in starting this treatment (beyond
24 hours) can compomise its efficacy (33).
It is, therefore, important to make the diagnosis quickly
and start treatment with plasma as soon as a clinical diagnosis
of TTP is made in the presence of hemolytic anemia, consumptive
thrombocytopenia without other apparent causes and an increase
in serum LDH levels.
Tthere are no indications on the number of sessions of plasma
exchange necessary in order to obtain a remission of the acute
phase. It is advisable to carry out daily sessions of plasma
exchange with an exchange of 3-5 liters of plasma until achieving
remission of clinical symptoms, a stable platelet count above
150x109/L, normalisation of serum
levels of LDH and correction of the anemia. It is also
recommended that daily treatment with plasma exchange is continued
for at least 3 days after the remission has been obtained
(34).
There are reports of genetically-based TTP in which prophylactic
treatment of recurrent episodes has been given, based on the
administration of plasma (30ml/Kg) at regular intervals (every
5-7 days) (34).
Several immunosuppressive treatments has been proposed in
association with plasma exchange for the treatment of acquired
form of TTP due to autoantibodies. These proposed treatments
include corticosteroids, intravenous immunoglobulins, splenectomy,
cytotoxic agents and anti-CD20 monoclonal antibodies (35,39).
Corticosteroids are almost always used in the acute treatment
of immune-mediated TTP, although the efficacy of this strategy
has not been demonstrated by controlled studies. The recommended
dose of prednisone is 1.0-1.5 mg/Kg. The efficacy of treatment
with lower doses in the prevention of relapses of chronic
recurrent forms of TTP has not been demonstrated, although
such treatment is often given. The dose used for high-dose
intravenous immunoglobulins treatment is 400 mg/Kg for 5 days
or 1g/Kg forr 2 days. Splenectomy, as in other blood diseases
with an autoimmune background, can be very considered in the
chronic, recurrent forms of TTP refractory to other treatments.
Its efficacy, which is by no means constant, is based on the
removal of an important site of production of anti-ADAMTS13
autoantibodies. In recent years there has been an increase
in the use of an anti-CD20 monoclonal antibody (rituximab)
in TTP, particularly in those cases not responding to treatment
with plasma exchange and characterised by multiple recurrences.
The aim of treatment with rituximab in TTP is to block the
production of anti-ADAMTS13 antibodies by depleting
B lymphocytes. The recommended dose is 375 mg/m2
every 7 days, repeated for three or four cycles.
Several case reports and small series suggest that rituximab
induces complete responses in the majority of patients with
TTP refractory to plasma exchange, corticosteroids and other
treatments such as vincristine or splenectomy. Responsens
to rituximab correlate with disappearance of ADAMTS13
inhibitors and a rise of the ADAMTS13 level into the
normal range (40).
Another category of drugs, whose use is still controversial,
is the inhibitor of platelet aggregate including ticlopidine,
clopidogrel, acetylsalicylic acid and dypiridamole. Their
use is not based on a pathogenic rationale, since the platelet
aggregation induced by the ULVWF multimers is not inhibited
by these drugs (9).
They must not, in any case, be used when the platelet count
is below 50x109/L, in order to
avoid increasing the risk of hemorrhage.
An algorithm for the treatment of TTP has been proposed in
2000 by George (5), based
on his experience in the management of a large cohort of patients
in Oklahoma and included in the Oklahoma TTP-HUS Registry
(Figure 1).
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