快猫短视频

A MOLECULE that was once the Cinderella of blood clotting has turned out to
be its linchpin. The discovery could open the way to a new generation of
anti-clotting drugs.

Researchers have long known the cast of characters involved in blood
clotting鈥攂oth in normal clotting and in the formation of life-threatening
blockages in arteries鈥攂ut not how they work together to form a clot. Now
scientists at the Australian Centre for Blood Diseases at Monash University
Medical School have developed a system of artificial blood vessels to model the
way blood clots form. Using this model, they have shown that the key role of
initiating clotting is taken by a poorly understood blood protein called von
Willebrand factor (vWf).

鈥淭he formation of blood clots is like an orchestra playing,鈥� says Ross Baker,
consultant haematologist at the Royal Perth Hospital, commenting on the
research. 鈥淢ost people appreciate that clotting involves the interaction of
fibrinogen and vWf with platelets, but the mechanism is still under
investigation. People have not had models to study it like this before.鈥�

Clots are principally made up of platelets鈥攕mall, sticky blood cells
that staunch bleeding by sticking to the lining of blood vessels and to one
another. Previous models suggested that platelets are bound together by the
protein fibrinogen, which latches onto receptors on the platelet surface.
快猫短视频s knew that vWf in the blood plasma also played a role, but the
function of small quantities of vWf found in the platelets themselves was more
of a mystery.

To study vWf, Monash doctoral student Su Kulkarni began looking at the blood
of patients with a rare form of a condition called von Willebrand disease. One
in every million people are born without any vWf in their blood platelets or
plasma. Unless treated, they can bleed to death.

Kulkarni added plasma containing plasma vWf and fibrinogen to blood from von
Willebrand patients flowing though the model blood vessels. This led to abnormal
clotting. By contrast, the blood clotted normally when Kulkarni added plasma vWf
and platelets containing vWf.

鈥淭he studies identify a pivotal role for vWf in platelets in starting the
clotting process,鈥� says Shaun Jackson, who led this research. 鈥淚t shows clotting
is much more complex than we initially thought. Our research shows that the
first protein in initiating clotting is platelet vWf, and that fibrinogen has a
subsequent role, probably in stabilising the clotting.鈥�

The work could lead to new kinds of anti-clotting drugs that block platelet
vWf. Such drugs might work either by preventing expression of the protein, or by
stopping it binding to other platelets.