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Acquired Deficiency of von Willebrand Factor-Cleaving Protease in a
Patient With Thrombotic Thrombocytopenic Purpura
Miha Furlan,
Rodolfo Robles,
Max Solenthaler, and
Bernhard Lämmle
From the Central Hematology Laboratory, University Hospital,
Inselspital, Bern, Switzerland.
Plasma of patients with thrombotic thrombocytopenic purpura (TTP)
has been shown to contain unusually large von Willebrand factor (vWF)
multimers that may cause platelet agglutination in vivo. Fresh frozen
plasma infusions and plasma exchange represent the most efficient
therapy of acute TTP. A specific protease responsible for cleavage of
vWF multimers has been recently isolated from normal human plasma and
was found to be deficient in four patients with chronic relapsing TTP.
We examined the activity of the vWF-cleaving protease in plasma samples
collected over a period of 400 days from a further patient with
recurrent episodes of TTP who was treated by plasma exchange, plasma
infusion, vincristine, corticosteroid therapy, and splenectomy.
Complete deficiency of the vWF-cleaving protease was established during
the first episode of TTP. The ensuing normalization of the platelet
count was associated with the appearance of the protease activity.
Three months after remission from the initial TTP event, the
vWF-cleaving protease again disappeared and the platelet count
gradually decreased. Relapses of severe thrombocytopenia occurred 7 and
11 months after the first acute episode of TTP. Deficient protease
activity was associated with the presence in the patient plasma of an
inhibitor that was found to be an IgG. Plasma exchange/infusion was
followed by a temporary increase in the antibody titer, whereas
treatment with vincristine led to a recovery of the platelet count
without affecting the inhibitor concentration. Splenectomy and
corticosteroid treatment resulted in disappearance of the autoantibody
and normalization of the protease activity and of the platelet count.
Our data suggest that the thrombocytopenia in this patient with TTP was
associated with a lack of the vWF-cleaving protease activity depleted
by an autoimmune mechanism. This case, together with our previously reported patients, leads us to conclude that acquired as well as
constitutional deficiency of the vWF-cleaving protease may predispose
to TTP.
Blood, Vol. 91 No. 8 (April 15), 1998:
pp. 2839-2846
© 1998 by The American Society of Hematology.
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