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Scripps Research scientist discovers natural molecule indirectly prevents stable clot formation
Date:2/1/2011

verting Heparin from an Anticoagulant into a Non-Anticoagulant

Heparin's anticoagulant activity is derived from a specific pattern of nitrogen- and oxygen-linked sulfation (or simply negative charges) that is recognized by anti-thrombin the inactivator of coagulation. However, in addition to binding to anti-thrombin heparin also binds to Platelet Factor 4, which is glittered with positive charge, and they attract one another like magnets.

Mosnier found heparin's anticoagulant activity could be prevented, and its Platelet Factor 4 binding selected for, by selectively removing the N-linked sulfations (and further acetylation). This effectively prevented heparin from being recognized by anti-thrombin and allowed it to instead take the Platelet Factor 4 out of the equation. This resulted in prevention of clot breakdown (fibrinolysis), by allowing TAFI to do its job.

To test the effectiveness of the modified heparin derivatives in enhancing clot stability, Mosnier employed a functional assay called a "clot lysis assay." Using a light scattering technique, plasma was used to generate a clot, which was degraded. Further modulation of the conditions allowed measurement of clot stability via TAFI activation. Mosnier found that, indeed, the modified-version heparin promoted clot stability.

Toward a Cheaper, Cost-Effective Treatment for Hemophilia A

An optimistic Mosnier admits his new discovery is in its infancy, but hopes it may one day provide an alternative treatment for bleeding conditions such as Hemophilia A.

Hemophilia A, which affects 1 in 5,000 males, is an X-linked genetic bleeding disorder whereby there is a reduced amount or activity of factor VIII. This results in the unstable clots, lacking fibrin a fibrous clot-forming protein. Currently, the treatment for Hemophilia A is prophylactically taking factor VIII as a medicine to improve clotting. Unfortunately, immunity against factor VIII
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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert

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