Thrombosis and Thrombolysis: Emphasis on Hemophilia and Effect of Clot Dissolution with Plasmin

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Title: Thrombosis and Thrombolysis: Emphasis on Hemophilia and Effect of Clot Dissolution with Plasmin
Author: Landskroner, Kyle Alan
Advisors: Dr. Gary Jesmok, Committee Chair
Dr. Lloyd Fleisher, Committee Co-Chair
Dr. Mark Papich, Committee Member
Dr. Ian Robertson, Committee Member
Dr. Neil C. Olson, Committee Chair
Abstract: The purpose of this research was to understand the mechanisms in which blood clots form and are degraded. The research studies examined the role of an endogenous protease, plasmin, which is found in all vertebrates, and the optimal doses of plasmin required to dissolve blood clots. When we investigated clot lysis with plasmin we examined blood clots from several species to which varying concentrations of plasmin were added, as well as varying methods of plasmin administration. The results of these studies not only highlighted important dose-response relationships of plasmin, but also demonstrated differences in the effect of human plasmin to dissolve blood clots compared to blood clot from the species tested. Porcine clots, in particular, were more resistant to lysis compared with human clots, while ovine clots had similar lysis compared with human clots. In addition, this research demonstrated that plasmin's effectiveness to lyse thrombi increases with an increase in clot surface area, e.g, by fragmentation, or when plasmin is administered as an intrathrombic administration. In separate studies, to investigate clot formation, we uesd mice that lack the FVIII protein. For these experiments we investigated the formation of blood clot formation using rotational thromboelastography (ROTEG) that measures the formation of fibrin in whole blood. This method was shown to be extremely sensitive to low levels of factor VIII protein and may have applications to classify particular phenotypes of hemophilia patients, or as a research tool to evaluate novel FVIII molecules.
Date: 2006-08-29
Degree: PhD
Discipline: Comparative Biomedical Sciences

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