Featured Research

from universities, journals, and other organizations

Abnormal Chemical Bonds Cause Bleeding Disorder

Date:
July 1, 2002
Source:
Washington University School Of Medicine
Summary:
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.

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, in which one amino acid in the protein has been replaced by another. Proponents of the conformational-change theory believe that the abnormal amino acid changes the shape of vWF, thereby causing it to bind with platelets when it shouldn't.

"It seems like a reasonable mechanism," says Diacovo, "but the evidence isn't there."

Diacovo suspected the answer lay in bond kinetics, which refers to how fast a bond can form and then dissociate. Earlier work on selectins, a family of proteins critical for recruiting circulating white blood to inflamed blood vessel walls, revealed that bond kinetics are responsible for controlling the interaction between these cells and the vessel wall. Diacovo theorized that the same was true for vWF and platelets.

To test the idea, Diacovo and a team of researchers studied the interaction of vWF and platelets using a variety of experiments, including some that involved mice and others that used flow chambers to duplicate the forces acting on platelets and vWF in circulating blood. The investigators discovered that a few bonds probably do form between vWF and platelets as they flow along in the bloodstream in healthy individuals. However, the number of bonds formed at any one time are too few to stabilize the attachment of platelets to vWF because as soon as a bond forms, it rapidly releases. In a particular form of von Willebrand's disease, however, the bonds last significantly longer than normal. That extra time allows many additional bonds to form, which stabilizes the interaction and locks the proteins and platelets together.

"It's not just a brief touch-and-go," says Diacovo. "Rather, one bond forms and before it breaks, two, three and four more have formed."

As more bonds form, small aggregates of platelets and vWF develop. These aggregates are cleaned from the blood, probably in the spleen, says Diacovo, which reduces the amount of vWF and the number of platelets in the blood. Consequently, people with von Willebrand's disease have a mild to moderate bleeding disorder. They bruise easily and simple nosebleeds can continue for several hours or days before finally healing.

In addition to providing insight into platelet function in normal individuals and in people with von Willebrand's disease, the findings may also help researchers develop new kinds of anti-thrombotic drugs. The results also may pose a new way to classify molecules, called adhesion receptors, found on the surface of cells.

###

Diacovo was recognized for this research with the 2002 Young Investigator's Prize in Thrombosis from the American Heart Association.

Doggett TA, Girdhar G, Lawshe A, Schmidtke DW, Laurenzi IJ, Diamond SL, Diacovo TG. Selectin-like kinetics and biomechanics promote rapid platelet adhesion in flow: the GPI balpha-vWF tether bond. Biophysical Journal, 83(1):194-205, July 2002.

Funding from the National Heart, Lung and Blood Institute and from the American Heart Association supported this research.

The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.


Story Source:

The above story is based on materials provided by Washington University School Of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

Washington University School Of Medicine. "Abnormal Chemical Bonds Cause Bleeding Disorder." ScienceDaily. ScienceDaily, 1 July 2002. <www.sciencedaily.com/releases/2002/06/020627010238.htm>.
Washington University School Of Medicine. (2002, July 1). Abnormal Chemical Bonds Cause Bleeding Disorder. ScienceDaily. Retrieved September 30, 2014 from www.sciencedaily.com/releases/2002/06/020627010238.htm
Washington University School Of Medicine. "Abnormal Chemical Bonds Cause Bleeding Disorder." ScienceDaily. www.sciencedaily.com/releases/2002/06/020627010238.htm (accessed September 30, 2014).

Share This



More Health & Medicine News

Tuesday, September 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How 'Yes Means Yes' Defines Sexual Assault

How 'Yes Means Yes' Defines Sexual Assault

Newsy (Sep. 29, 2014) Aimed at reducing sexual assaults on college campuses, California has adopted a new law changing the standard of consent for sexual activity. Video provided by Newsy
Powered by NewsLook.com
Scientists May Have Found An Early Sign Of Pancreatic Cancer

Scientists May Have Found An Early Sign Of Pancreatic Cancer

Newsy (Sep. 29, 2014) Researchers looked at 1,500 blood samples and determined people who developed pancreatic cancer had more branched chain amino acids. Video provided by Newsy
Powered by NewsLook.com
Colo. Doctors See Cluster of Enterovirus Cases

Colo. Doctors See Cluster of Enterovirus Cases

AP (Sep. 29, 2014) Doctors at the Children's Hospital of Colorado say they have treated over 4,000 children with serious respiratory illnesses since August. Nine of the patients have shown distinct neurological symptoms, including limb weakness. (Sept. 29) Video provided by AP
Powered by NewsLook.com
Dr.'s Unsure of Cause of Fast-Spreading Virus

Dr.'s Unsure of Cause of Fast-Spreading Virus

AP (Sep. 29, 2014) Doctors at the Children's Hospital of Colorado say they have treated over 4,000 children with serious respiratory illnesses since August. Nine of the patients have shown distinct neurological symptoms, including limb weakness. (Sept. 29) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins