Fibrinogen inhibits the heparin cofactor II-mediated antithrombin activity
of dermatan sulfate
A Zammit and J Dawes
Heart Research Institute, Sydney, Australia.
Dermatan sulfate is a naturally occurring antithrombotic glycosaminoglycan.
The antithrombin activity of several dermatan sulfate preparations has been
measured in whole human plasma and found to be -55% of that in purified
systems. Kinetic studies under pseudo- first-order conditions indicated
that the reduction in antithrombin activity of dermatan sulfate in plasma
compared with that in buffer was due to noncompetitive inhibition with
respect to dermatan sulfate. Analysis of the protein profile bound to
immobilized dermatan sulphate showed that on a molar basis, histidine-rich
glycoprotein and apolipoprotein E were the most abundant proteins
specifically bound, together with significant amounts of fibrinogen and
vitronectin. Addition of these proteins to the purified system showed that
only fibrinogen inhibited the antithrombin activity of dermatan sulfate and
that it did so in a concentration-dependent manner over the physiologic
range of plasma fibrinogen levels. These results indicate that the
anticoagulant activity of dermatan sulfate may be modulated in human plasma
by fibrinogen.
Volume 85,
Issue 3,
pp. 720-726,
02/01/1995
Copyright © 1995 by The American Society of Hematology
