Program Project Grant for Genetic Studies of Common Bleeding Disorders

Von Willebrand disease

The Medical College of Wisconsin has received a five-year, $9.7 million National Heart, Lung and Blood Institute Program Project Grant for genetic studies to improve the molecular and clinical understanding of Von Willebrand disease (VWD), the most common hereditary bleeding disorder.

Pediatric hematologist Robert R. Montgomery, M.D., professor of pediatrics at the Medical College and senior researcher at the Blood Research Center of the BloodCenter of Wisconsin, is principal investigator for the grant.

Von Willebrand disease is caused by a deficiency of von Willebrand factor (VWF), which is necessary for normal blood clotting. The disease affects both men and women. Most cases are mild, but aspirin and other nonsteroidal anti-inflammatory drugs can make the condition worse. Women may suffer very heavy menstrual bleeding, and family history of a bleeding disorder is the primary risk factor.

"There is a lack of understanding of the genetic causes of low or abnormal VWF, and the molecular mechanisms involved in the disorder," says Dr. Montgomery. "While a large number of individuals have low VWF with abnormal bleeding symptoms, it is not scientifically clear if this is a disease, or if VWF is a continuous risk-factor for bleeding. For many practicing physicians, the general understanding of this group of disorders has not been optimal, and how to evaluate and treat these patients has been unclear."

The program involves three distinct research projects* and two core facilities, one for administrative support and participant recruitment, and another for clinical laboratory and genetic sequencing services. The projects will determine the clinical and genetic characteristics of a large number of VWF patients as well as carriers of genes for various forms of the disease. They will also explore the impact specific combinations of these genes and unrelated genetic mutations may have on individuals and families, in terms of their clinical symptoms and other traits revealed by laboratory analysis.

Dr. Montgomery's co-investigators at the Medical College and Children's Hospital of Wisconsin are: Sandra L. Haberichter, Ph.D., assistant professor of pediatrics; Joan Cox Gill, M.D., professor of pediatrics; Raymond G. Hoffmann, Ph.D., professor of biostatistics; Veronica H. Flood, M.D., assistant professor of pediatrics; J. Paul Scott, M.D., professor of pediatrics; Cheryl A Hillery, M.D., professor of pediatrics, and Kenneth D. Friedman M.D., associate professor of medicine.

The program project grant mechanism is designed to support synergistic research, in which the funding of several interdependent projects as a group offers significant scientific advantages over supporting these projects as individual research grants.

*Projects are located at the Blood Research Institute, the Medical College of Wisconsin, and Queen's University in Canada together with Sheffield University in the United Kingdom. Samples from VWD patients at Primary Treatment Centers in Atlanta, Detroit, Iowa City, Indianapolis, Houston, New Orleans, and Pittsburgh will be tested at BloodCenter's Hemostasis Lab. Patient recruitment will also be carried out at other centers through the Hemophilia and Thrombosis Research Society, a North American organization whose national offices are incorporated here in Milwaukee. The BloodCenter's Comprehensive Center for Bleeding Disorders will serve as the primary collection center for local participants.