Factor XI Deficiency Clinical Trial
Official title:
The Influence of the Proteins of the Contact Activation System on Thrombus Formation in Human Blood
Cardiovascular diseases are important causes of morbidity and mortality in the
industrialized world. Abnormalities in the coagulation system, causing a hypercoagulable
state, are a known risk factor for arterial and venous thrombosis. The contact activation
system is part of the coagulation system and consists of four proteins: coagulation factor
XII (FXII), FXI, prekallikrein and high molecular weight kininogen (HMWK). Clinical studies
indicate an important role for the contact activation system on the risk of arterial
thrombosis. Furthermore, there is substantial evidence from mouse studies that FXII and FXI
participate in the formation and stability of thrombi. In vitro studies show that collagen,
present in the vascular wall, is able to activate FXII and hereby stimulate thrombin
formation and potentiate the formation of platelet-fibrin thrombi and FXIIa is able to
change the structure of fibrin clots by binding to fibrin(ogen) and by generation of
additional thrombin. However, the contact system also participates in the process of
fibrinolysis, which degrades thrombi.
The investigators would like to investigate the contribution of the contact activation
system to the formation of thrombi. The formation of a thrombus within the vascular bed is
the main cause for occlusion of an artery or vein, which can lead to an infarct such as a
heart attack. Due to the other functions of the contact system it is important to fully
understand how the contact system contributes to thrombus formation, before it can be used
as a target in the treatment of arterial thrombosis. The aim of this study is to determine
the contribution of the proteins of the contact system, mainly FXII and FXI, in the platelet
mediated formation and degradation of thrombi. This will be studied in flow models
(perfusion-flow model and Chandler loop), in a static model (ROTEM®) and using thrombin
generation assay.
n/a
Intervention Model: Single Group Assignment, Masking: Open Label