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Racial difference in blood clotting warrants a closer look at heart attack medications
Date:11/10/2013

rmation of a platelet plug that clogs blood vessels and can lead to heart attack or stroke. However, there is considerable variability in how patients respond to these medications, which confounds physicians who must deduce the appropriate drug and proper dose for each patient. Now, researchers from Thomas Jefferson University have identified some of the genetic differences behind these variations, which could help doctors treat racial groups with a more personalized and effective approach.

"Differences in platelet biology could be part of the explanation of the disparity," says Dr. Bray.

To investigate whether the variation among different individuals had a racial component, Dr. Bray and collaborators from Baylor Medical College, Harvard Medical School and the New York and Puget Sound Blood Centers analyzed platelets from blood samples of 154 young healthy subjects that included 70 blacks and 84 whites. Self-reported race was confirmed with genetic tests that verified geographic (African or European) ancestry. Unexpectedly, the researchers found that platelets from black donors clotted faster and to a greater extent in response to the naturally occurring clotting agent, thrombin that specifically triggered one of the platelet-activating receptors, called PAR4. No racial differences were seen with other clotting agents.

Thrombin is the most potent platelet activator in the body, and it is targeted for suppression by numerous blood-thinning medications. However, newer drugs that target thrombin inhibit specific members of the PAR family of receptors. For example, the drug vorapaxar, currently in development for patients with a history of heart disease, specifically inhibits the PAR1 receptor. If PAR1 is blocked by vorapaxar, then PAR4 is the only means by which thrombin can activate platelets, and the Jefferson scientists showed that in this setting thrombin more potently activated platelets from blacks. It remains to be determined how o
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Contact: Edyta Zielinska
edyta.zielinska@jefferson.edu
215-955-5291
Thomas Jefferson University
Source:Eurekalert

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