Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients with FXI or FXII deficiency | Experimental | 12 patients with FXI deficiency and 6 patients with FXII deficiency |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Global Haemostasis assays | Other |
|
| Measure | Description | Time Frame |
|---|---|---|
| fibrinolytic degradation rate of the formed clots by ROTEM analysis | 1 day (cross sectional) |
| Measure | Description | Time Frame |
|---|---|---|
| the ex-vivo formation of platelet-mediated thrombi on collagen in a perfusion flow mode | 1 day (cross sectional) | |
| biochemical composition of the thrombi formed in the Chandler loop | 1 day (cross sectional) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yesim DARGAUD, MD PHD | Contact | (0)4 72 11 88 25 | +33 | ydargaud@univ-lyon1.fr |
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Unité d'Hémostase Clinique Hôpital Louis Pradel | Recruiting | Bron | 69500 | France |
Not provided
| ID | Term |
|---|---|
| D005173 | Factor XI Deficiency |
| D005175 | Factor XII Deficiency |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| endogenous thrombin potential (ETP) of the platelet rich plasma of these patients | 1 day (cross sectional) |
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |