Abnormal chemical bonds cause bleeding disorder

St. Louis, June 24, 2002 Blood platelets and the protein von Willebrand factor (vWF) normally pass like strangers in the night until an artery is injured. Then, they recognize one another and latch together to form a blood clot and prevent further bleeding. In a few people, though, the two "embrace" prematurely, leading to a bleeding disorder known as type IIb von Willebrand's disease.

Researchers at Washington University School of Medicine in St. Louis have a new explanation for why and how this pair embraces abnormally to cause the disease. Their work is published in the July issue of Biophysical Journal.

The study suggests that the disease occurs because a defective form of vWF causes chemical bonds to persist longer than they should, thereby holding vWF and blood platelets together in flowing blood when they shouldn't. That is, the defect in the vWF protein changes the kinetics of the chemical bonds that form between the protein and the platelets.

"This is the first time that a naturally occurring disease has been linked to an alteration in the kinetic properties of a chemical bond," says study leader Thomas G. Diacovo, M.D., assistant professor of pediatrics and of pathology and immunology. "The finding should give us a better understanding of how normal platelets function and of the delicate balance that exists between these blood-clotting elements, disturb that balance, and the whole system falls apart."

For the past 25 years, scientists have tried to explain why platelets normally adhere to vWF at sites of vascular injury but not in flowing blood. Most of them believe that docking sites on vWF undergo a change in shape after the protein adheres to a site of vessel injury. This change presumably allows passing platelets to attach to vWF. Biology has many examples of such conformational changes that transform molecules from an inactive to an active state. People with von Willebrand's disease have an altered form of vWF,

Contact: Darrell E. Ward
Washington University School of Medicine

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