It has been generally considered that platelets
are less important in venous thrombus formation.
However, clinical studies have shown an association
between venous thromboembolism (VTE) and von
Willebrand factor (VWF). We therefore investigated the
contribution of VWF and platelet interaction to the onset
of VTE using tissues from autopsies and from an animal
model. An immunohistochemical study revealed that
glycoprotein (GP) IIb/IIIa, fibrin, glycophorin A
(erythrocyte-specific protein) and VWF were
consistently localized in ilio-femoral venous thrombi and
in pulmonary thromboemboli from 8 autopsied cases
who died of VTE, and VWF was closely associated with
GPIIb/IIIa and fibrin. Venous thrombi and pulmonary
emboli contained significant amounts of GPIIb/IIIa and
VWF, in addition to glycophorin A and fibrin, and the
factors did not significantly differ between them. A
rabbit model of VTE was developed by inserting a
polyethylene tube into the iliac vein. The constituents of
the induced thrombi were quite similar to those of
human VTE. An antibody against VWF (AJW200),
which inhibits interactions between the VWF A1 domain
and platelet GPIb, significantly reduced venous
thrombus formation and pulmonary thromboembolism in
the model. These results suggest that VWF A1-platelet
GPIb interaction plays a significant role in venous
thrombus formation