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SUMMARY : during this doctorate, we evaluated how the presence of von Willebrand factor (VWF) multimers in plasma is regulated and how this process might influence the onset of thrombotic thrombocytopenic purpura (TTP) and myocardial infarction (MI). We demonstrated that: - salts, and particularly anions, in physiological conditions determine an inhibition of VWF cleavage by ADAMTS-13, causing a conformational change of the VWF. Finally we demonstrated the presence of a negative association between the GpIb or ristocetin binding and ions binding to VWF; - TSP-1 display a inhibiting effect on ADAMTS-13 activity and the entire A1A2A3 region is necessary to achieve an optimal inhibition. The A3 domain plays a central role, although its effect is dependent on the allosteric role of the A1 domain; - an association between the N700S polymorp...
Considerable progress has been made in determining the molecular bases of inherited thrombophilia in the last 25 years. There are several genetic abnormalities that can be detected in the laboratory and are currently recognized to be unequivocally associated with an increased tendency to develop venous thrombosis. Testing for inherited and acquired causes of thrombophilia may make counseling more focused in ostensibly healthy members of thrombophilic families (i.e., those in which a measurable abnormality was identified in one or more asymptomatic persons). In other situations, including women who start taking oral contraceptives, become pregnant, or consider hormone replacement therapy, screening is generally not useful. It is hoped that because we currently have such simple and clinically useful global tests of hypocoagulability as t...
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