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Degradation of von Willebrand factor in patients with acquired clinical
conditions in which there is heightened proteolysis
AB Federici, SD Berkowitz, A Lattuada and PM Mannucci
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, RCSS Maggiore
Hospital, Milan, Italy.
The behavior of plasma von Willebrand factor (vWF) in patients with acute
leukemia (n = 5), decompensated cirrhosis (n = 10), and acute pancreatitis
(n = 5) was investigated to evaluate whether the systemic proteolytic
states associated with these diseases had affected the structure and
function of the molecule. vWF antigen and, to a lesser degree, ristocetin
cofactor activity in patient plasma were high. Multimeric analysis of
plasma vWF revealed loss of high molecular weight multimers. The subunit
composition and proteolytic pattern of vWF immunopurified from patient
plasmas and reduced were studied by sodium dodecyl sulfate
(SDS)-polyacrylamide gel electrophoresis followed by transblotting and
probing with monoclonal antibodies that distinguish cleavages caused by
plasmin from those caused by other proteases. There was marked reduction of
the relative concentration of the native vWF subunit of 225 Kd in all
patient groups, indicating heightened cleavage of the protein. The
concentrations of 189- and 140- Kd vWF fragments, normally present in
plasma, were increased in cirrhosis and pancreatitis but not in leukemia.
Novel fragments, ranging in size from less than 225 to approximately 120 Kd
were present in leukemia and cirrhosis, including plasmin-generated
fragments of 176 and 145 Kd. These data indicate that in clinical
conditions in which there is heightened proteolysis vWF is degraded in vivo
by plasmin and other proteases. Degraded vWF may be less effective than
native vWF in supporting primary hemostasis, thereby being a cofactor in
the multifactorial bleeding diathesis accompanying systemic proteolytic
states.
Volume 81,
Issue 3,
pp. 720-725,
02/01/1993
Copyright © 1993 by The American Society of Hematology
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