Seeking Markers for Menopausal Women at Risk for a Deadly Blood Clot

In women, hormone therapy is a risk factor for venous thrombosis, a blood clot forming deep inside the vein. Despite the fact that the disorder is rare, it increases exponentially during menopause and can be deadly. The hormone trials conducted thus far, focusing on proteins in blood coagulation, have not yet led to a risk profile, thereby precluding identification of women at risk. Now, a team of Mayo Clinic researchers, led by Virginia Miller, has developed a novel concept that uses blood platelets to define thrombotic risk. The team is testing its theory as part of the Kronos Early Estrogen Prevention Study (KEEPS). Miller is discussing the research at a conference being sponsored by the American Physiological Society (APS).

Miller’s colleagues are Muthuvel Jayachandran, Kazaumori Kashimoto, John A. Heit and Whyte G. Owen, all with the Department of Surgery, Physiology and Bioengineering, Biochemistry and Molecular Biology and Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN. Their work is entitled “Sex Steroids, Platelet Aggregation and Inflammation,” and is among the 120 presentations being offered at the conference, Sex and Gender in Cardiovascular-Renal Physiology and Pathophysiology, being held August 9-12, 2007 at the Hyatt Regency Austin on Town Lake, Austin, TX. The event is the second scientific gathering to be sponsored by the American Physiological Society this year.

A New Approach to Assessing Clot Risk in Menopausal Women
The study focuses on platelets, which are cellular fragments in the blood. Platelets have a phenotype (i.e., a set of physical characteristics) that change and it is known that hormones affect platelet change. The team is examining what happens to platelets in the presence of hormones – whether platelet microvesicles occur more frequently as a result, if a change is triggered by infection, and what may account for thrombotic risk in one woman over another.

The study design takes into account the researchers’ belief that three forces – an injury, a platelet effect at the injury, and the inflammation that affects the platelet and the vessel wall – are involved in the development of thrombotic risk. The study builds on the team’s earlier findings in an animal model. They are applying the earlier results to a human population for the first time using blood taken from the women enrolled in the KEEPS trial. Depending upon the results from this group, a larger trial of 720 samples will be examined.

Depending on the results of this study, the researchers may examine the relationship of platelet activity, inflammation, and cardiovascular risk (CV) in men. It is well known that men have a higher risk factor for cardiovascular disease (CVD) than do females, and arterial clots, rather than venous clots, are a greater concern in the presence of CVD. Since men carry the female hormone estrogen as well as the male hormone testosterone, some of the findings from the female KEEPS study may shed light on these mechanisms involving men.