Scientist Discovers Crucial Part of Blood-clotting Process

A researcher at The University of Texas Health Center at Tyler has discovered how a small but crucial part of the blood-clotting process works. Once the process is thoroughly understood, synthetic chemicals can be designed to regulate it, thus preventing excessive bleeding or blood clotting. The findings of Pierre Neuenschwander, Ph.D., and his team are published in the Aug. 11, 2006, edition of the Journal of Biological Chemistry.

Dr. Neuenschwander, an associate professor of biochemistry, and his team are investigating one step in the blood-clotting process that involves factor IXa, an enzyme (IX and the other factors are read as Roman numerals). Enzymes are proteins that change the rate of chemical reactions without needing an external energy source, such as heat.

"If you don't have factor IXa, you have hemophilia, or excessive bleeding, and your blood doesn't clot properly. So you have to have factor IXa, but not too much of it. If it's left unregulated, you get clots where you don't want them and end up with strokes and heart attacks," Dr. Neuenschwander said.

"It's been difficult to study how factor IXa works. It's not usually a very active enzyme. This research paper is one of the first to show that a physiologically relevant molecule, heparin, can modulate the activity of factor IXa," he said. Heparin is a naturally occurring mixture of compounds that prevents unwanted blood clotting. It is a molecule with many places where enzymes and other substances can bind to activate or stop biochemical reactions in the cell.

By revealing how factor IXa works, it should be possible to make synthetic chemicals that prevent strokes and heart attacks, Dr. Neuenschwander said. Conversely, you could make synthetic activators that could stop the unwanted bleeding that occurs in hemophilia, he added.

Dr. Neuenschwander has been investigating factor IXa for the past six years. His first research was funded by a small grant from the American Heart Association. Currently, his research is funded by a five-year, $1.375 million grant from the National Institutes of Health that ends in 2010. The NIH grant originally was for just four years; the NIH thought enough of Dr. Neuenschwander's research to award him another year of funding.

He and his team plan to spend the next year experimenting with antithrombin, a small naturally occurring molecule that inactivates several enzymes involved in the coagulation process. They hope to gain understanding of another step in that process.

"We want to see if we can design inhibitors that would mimic what heparin does. Our goal is to develop these and eventually test them in clinical trials," Dr. Neuenschwander said.

Dr. Neuenschwander is the lead author of the article on how heparin regulates factor IXa. Co-authors are Kimberly J. Baker-Deadmond, Ph.D., a postdoctoral fellow in Dr. Neuenschwander's lab; Stephen R. Williamson, a UTHCT lab technician; and Armen Nalian, a collaborator of Dr. Neuenschwander's at Stephen F. Austin State University in Nacogdoches, Texas.