The Use of Rituximab in Acute Thrombotic Thrombocytopenic Purpura (TTP)
Status:
Unknown status
Trial end date:
2010-06-01
Target enrollment:
Participant gender:
Summary
TTP is a rare and serious blood disorder, characterized by the formation of small clots
(micro thrombi) within the circulation and can be fatal. The formation of blood clots occurs
primarily in the smaller blood vessels, the arterioles and capillaries, associated with
multisystem organ involvement, especially the brain and kidneys. TTP has an incidence of
approximately 1-3 people/million of the population/year.
TTP is due to a decrease in an enzyme, ADAMTS 13 that is released by cells lining blood
vessels (endothelial cells). ADAMTS 13 'cleaves' or breaks down very large von Willebrand
Factor (vWF) strands. vWF is used in blood clotting. Deficiency or inhibition of the enzyme,
results in release of the ultra large vWF into the circulation. Platelets bind to these ultra
large vWF multimers, promoting blood clot formation and platelet consumption
(thrombocytopenia). In more then 70% of TTP cases no precipitating cause can be found and the
majority of these patients have antibodies against ADAMTS 13. Plasma Exchange (PEX) was
introduced in the management of TTP in 1977 and the mortality of TTP patients has since
decreased from approximately 90% to 15-20%. PEX is essential in TTP treatment as plasma
contains the missing enzyme ADAMTS 13.
Rituximab (licensed and internationally used monoclonal antibody) selectively acts on white
blood cells known as B-lymphocytes or B cells that produce the antibody to ADAMTS 13. By
inhibiting ADAMTS 13 antibody production, ADAMTS 13 activity increases, resulting in
remission. Rituximab has been used in our institutions in patients with acute TTP that are
refractory to standard treatment - PEX. The resulting remission has been dramatic, with a
non-toxic side effect profile and no patients to date has relapsed (longest follow-up 19
months) following Rituximab therapy. Therefore, we plan to use Rituximab with PEX in patients
who present with acute TTP.