Enzyme Defective in Bleeding Abnormality.

Researchers the University of California, San Diego (UCSD) School of Medicine (9500 Gilman Dr., La Jolla, CA 92093; Tel: 858/534- 2230; Website: www.ucsd.edu) found that mutations in an enzyme, sialyltransferase ST3Gal-IV, greatly reduced levels of von Willebrand factor (VWF) in mice, by a mechanism also seen in some human patients with clinical signs of bleeding abnormalities and abnormally low levels of VWF. This study was published in the July 23, 2002 issue of the Proceedings of the National Academy of Sciences (PNAS).

The ST3Gal-IV enzyme normally acts by adding a sialic acid to certain blood factors that regulate clotting. The mutated version is unable to produce this sialic acid.

The level of VWF, a blood element involved in clotting, is a major determinant of the severity of von Willebrand disease (VWD), which is the most prevalent bleeding disorder in humans, affecting more than three million Americans. VWD patients have such symptoms as easy bruising, heavy or prolonged menstrual periods, frequent nosebleeds or prolonged bleeding after injury, surgery, childbirth, or dental work.

The study's senior author, Jamey D. Marth, a UCSD professor of cellular and molecular medicine and an investigator with the Howard Hughes Medical Institute, notes that the level of VWF in both mouse and human blood is highly variable, but must stay within a narrow range to avoid either excess bleeding or dangerous clotting that can lead to heart attack or stroke.

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