Subunit composition of plasma von Willebrand factor in patients with the
myeloproliferative syndrome
U Budde, JA Dent, SD Berkowitz, ZM Ruggeri and TS Zimmerman
In order to evaluate the role of proteolysis in acquired von Willebrand's
disease (vWD) associated with the myeloproliferative syndrome, we have
determined the relative quantity of von Willebrand factor (vWF) fragments
as compared with the intact 225 kDa subunit in four patients. The plasma
vWF of each individual lacked large multimers; each had a prolonged
bleeding time; and both platelet and leukocyte counts were elevated. Plasma
was obtained from blood drawn into 1 mmol/L leupeptin, 6 mmol/L
N-ethylmaleimide, and 5 mmol/L EDTA to prevent in vitro proteolysis. vWF
was isolated from plasma by immunoadsorbent chromatography, reduced,
subjected to SDS-5% polyacrylamide gel electrophoresis, and immunoblotted
with a mixture of 55 anti-vWF monoclonal antibodies. In three patients with
essential thrombocytosis (ET) the 176 and 140 kDa fragments were increased
in proportion to the intact 225 kDa subunit indicating increased
proteolysis. Treatment of one ET patient with CCNU (Lomustine) decreased
the platelet count and, to a lesser extent, the white blood cell count.
This was associated with a correction of the bleeding time, a partial
correction of the multimeric abnormality, and a lessening of vWF cleavage.
In a patient with polycythemia rubra vera (PRV) the proportion of the 176
kDa fragment was increased to the upper limit of normal but there was no
definite evidence of increased proteolysis. These studies provide evidence
that proteolysis plays a role in the acquired von Willebrand's disease
associated with the myeloproliferative syndrome. However, other mechanisms
must also be considered.
Volume 68,
Issue 6,
pp. 1213-1217,
12/01/1986
Copyright © 1986 by The American Society of Hematology
