Clinical Trial: The Proteins of the Contact Activation System

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: The Influence of the Proteins of the Contact Activation System on Thrombus Formation in Human Blood

Brief Summary:

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 generat

Detailed Summary:
Sponsor: Hospices Civils de Lyon

Current Primary Outcome: fibrinolytic degradation rate of the formed clots by ROTEM analysis [ Time Frame: 1 day (cross sectional) ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • the ex-vivo formation of platelet-mediated thrombi on collagen in a perfusion flow mode [ Time Frame: 1 day (cross sectional) ]
  • biochemical composition of the thrombi formed in the Chandler loop [ Time Frame: 1 day (cross sectional) ]
  • endogenous thrombin potential (ETP) of the platelet rich plasma of these patients [ Time Frame: 1 day (cross sectional) ]


Original Secondary Outcome: Same as current

Information By: Hospices Civils de Lyon

Dates:
Date Received: May 25, 2016
Date Started: June 2015
Date Completion: September 2016
Last Updated: May 30, 2016
Last Verified: May 2016