Inflammation Linked to Deep Vein Thromboses

Deep vein thromboses, or DVTs, are a serious health problem, especially in the elderly. When blood clots form in deep leg veins, they can permanently damage the venous system or even be fatal, if a clot travels to the lungs.

Until recently, deep vein thromboses were thought to be solely a blood or vascular disorder. Now, U-M Medical School scientists have discovered intriguing new evidence to support the idea that the development of blood clots in veins — just like blocked arteries in atherosclerosis — is an inflammatory process.

Daniel Myers and Thomas Wakefield Photo: Martin Vloet

"When a blood clot develops in superficial veins of the leg — a condition called phlebitis — the redness and swelling associated with inflammation are visible," says Thomas W. Wakefield, M.D., a professor of surgery in the medical school and a vascular surgeon in the U-M Cardiovascular Center. "When a clot forms deep inside the leg, these signs are hidden, so physicians have rarely associated DVTs with inflammation."

Working with Daniel D. Myers, D.V.M., an assistant professor of vascular surgery and animal medicine in the medical school, Wakefield is trying to figure out exactly what happens inside veins when a blood clot develops. In a recent research study with genetically engineered mice, he and Myers discovered that inflammatory molecules and immune system cells play a major role in the process.

One strain of mice used in the study had a genetic mutation, which caused them to have abnormally high levels of a pro-inflammatory molecule called P-selectin circulating in their blood plasma. A second group of mice lacked the gene required to produce P-selectin. The mice were surgically treated to induce thrombosis in the major vein carrying blood from the lower body back to the heart.

Myers and Wakefield found that mice with the highest levels of P-selectin in their blood developed the largest venous blood clots and had more inflammatory cells in their vein walls. Blood from mice with high levels of P-selectin also contained microparticles — small fragments of cell membrane from degraded cells, which accelerate the clot-forming process.

Wakefield says the ultimate goal of his research is finding new ways to inhibit clot formation in his patients by using an anti-inflammatory approach, instead of relying on anticoagulants to treat DVT after it develops. "All current blood-thinning medications can cause serious bleeding problems in patients, so there's a need for new treatment options," he says. "The more we understand about the mechanism of DVT formation, the better our chances of finding safer ways to treat it."

The study was funded by the National Institutes of Health and Wyeth Research of Cambridge, Massachusetts.

-SFP

Read an expanded version of this story:
www.med.umich.edu/opm/newspage/2003/venous.htm

For more information on deep vein thromboses:
www.med.umich.edu/1libr/aha/aha_dvthromb_sha.htm