Blood Markers Might Predict Clotting Risk With HRT

SATURDAY Dec. 8, 2007 -- Levels of certain blood markers may increase the risk of clotting in women taking hormone replacement therapy to relieve symptoms of menopause, new research shows.

These markers might need to be considered when deciding whether to take the hormone therapy, said the authors of a study being presented Saturday at the American Society of Hematology annual meeting in Atlanta.

Hormone replacement therapy (HRT) roughly doubles the risk of venous thrombosis (VTE), or blood clots in the veins (most commonly in the legs). The risk is increased even further as the woman ages, and if she is obese or has other risk factors for clotting.

For a woman in her 50s not taking hormones, the risk of developing a VTE is one or two per 1,000 thousand people per year. With hormones, the risk increases to two to four per 1,000 per year.

"The challenge is that women who want to take hormones for relief of menopausal symptoms are at risk for thrombosis," said study author Dr. Mary Cushman, director of the Thrombosis and Hemostasis Program at the University of Vermont, in Burlington. "We wanted to see if we could determine factors that would make the risk of hormones even higher."

The group looked at women who had been part of the Women's Health Initiative (WHI), a large, government-sponsored study which investigated the most common causes of death and low quality of life among postmenopausal women.

The best-known findings are those of clinical trials looking at HRT. Women taking estrogen plus progestin had an increased risk of heart attack, stroke, blood clots and breast cancer than women taking the placebo. Women taking estrogen alone had an increased risk of stroke and blood clots, an uncertain effect for breast cancer and no difference in the risk for heart attack.

For this analysis, 215 women taking hormones who developed VTE were compared with a control group, also taking hormones, who did not develop VTE during a follow-up of about four years.

Raised levels of two factors which reflect the clotting activity of the blood increased the risk of thrombosis events. Elevated levels of D-dimer predicted a 2.8-fold increased risk of thrombosis, while elevated levels of prothrombin fragment 1.2 predicted a 1.9-fold increased risk.

On the flip side, lower levels of anti-coagulant proteins, or proteins which are natural blood thinners, also increased the risk of clotting. Lower levels of protein C were linked with double the risk, lower protein S with triple the risk, and lower levels of antithrombin were associated with a 1.7-fold increased risk.

The most important factor turned out to be elevated D-dimer, which is present in 25 percent of women and which increased the risk of thrombosis in women receiving HRT sixfold.

"That gets in the range of 1 percent of women a year, so that's pretty significant clinically," Cushman said. "You might think a little harder if you want to take hormones, or take them for a minimal amount of time."

Not everyone considering HRT needs to get their D-dimer tested, however.

"The bottom line is that for some women who are concerned and their doctor wants to do something to try to help determine risk, D-dimer might be warranted," Cushman said. The test for D-dimer is available commercially.

"The study is provocative, but I can't see it as going to the bedside for patients when deciding who goes on HRT," said Dr. Steven Deitelzweig, system department chair of hospital medicine and vice president of medical affairs at Ochsner Health Systems, in New Orleans. "These are pretty unusual markers. There might be some implications for people with a personal or family history. For a select group, it gives vascular experts additional tools to bring to the benefit of patients."

And Cushman noted these blood markers do not tell the whole story.

"There's not one single thing that causes venous thrombosis. You might live life with higher D-dimer and never get a blood clot because the circumstances just aren't right," Cushman said. "But we know from previous work that obesity enhances the risk with hormones so if you were obese and thinking about taking hormones and your D-dimer was high, these things all add together. The context has to be considered in decision-making. For any individual person, her doctor needs to review all of her risk factors when considering taking hormones."

More information

Visit the National Heart, Lung, and Blood Institute for more on the Women's Health Initiative.

Posted: December 2007


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