Thrombus Formation Under Different Flow-conditions
Rationale: Cardiovascular diseases are important causes of morbidity and mortality in the industrialized world. Clinical studies indicate an important role for the proteins of the contact activation system (coagulation factor XII (FXII), FXI, prekallikrein and high molecular weight kininogen (HMWK)) on the risk of cardiovascular disease. There is substantial evidence from mouse studies that FXII and FXI participate in the formation and stability of thrombi and in vitro studies showed that collagen is able to activate FXII and hereby stimulate thrombin formation and potentiate the formation of platelet-fibrin thrombi. The investigators want to determine the role of the proteins of the contact activation system in platelet mediated thrombus formation in human blood.
Objective: The investigators will study the effects of the proteins of the contact activation system on platelet mediated thrombus formation, embolization and degradation on collagen in a perfusion flow model.
Study design: Blood will be collected from human volunteers via a venipuncture in the forearm. Each volunteer will donate maximally four times 30 ml of blood over a period of two days. This blood is used in perfusion flow experiments: blood flows over a coverslip covered with collagen in a flow chamber. The investigators will vary several conditions such as the concentration of the proteins and the shear rate. For perfusion flow experiments, the investigators need fresh whole blood because platelets are viable for four hours. After this time, new blood is needed.
Study population: For this study the investigators need blood from human volunteers with a coagulation defect in one of the proteins of the contact activation system, e.g. FXII, FXI, prekallikrein or HMWK and controls without any coagulation defects.
Main study parameters/endpoints: The investigators main study endpoint is the ex vivo formation of platelet-mediated thrombi on collagen in a perfusion flow model. The investigators hypothesize that thrombi formed from blood of patients deficient in FXII or FXI are less stable than those formed from blood from controls.
|Study Design:||Time Perspective: Cross-Sectional|
|Official Title:||The Influence of the Proteins of the Contact Activation System on Thrombus Formation Under Different Flow-conditions in Blood|
- Thrombus formation, stability and break down [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]Using perfusion-flow experiments the formation, stability and break down of clots formed from the blood of the study participants will be determined.
Biospecimen Retention: Samples Without DNA
- Whole blood
- Platelet poor plasma
|Study Start Date:||May 2011|
|Estimated Study Completion Date:||May 2013|
|Estimated Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
Factor XII deficiency
Patients deficient in coagulation factor XII
Factor XI Deficiency
Patients deficient in coagulation factor XI
Patients deficient in prekallikrein
Patients deficient in high molecular weight kininogen (HMWK)
|Contact: Joke Konings, MSc||+31-433881542||J.Konings@maastrichtuniversity.nl|
|Contact: José WP Govers-Riemslag, PhD||+31-433884263||J.Govers@maastrichtuniversity.nl|
|Maastricht, Limburg, Netherlands, 6229 ER|
|Contact: Joke Konings, MSc +31-433881542 J.Konings@BIOCH.unimaas.nl|
|Contact: José WP Govers-Riemslag, PhD +31-433884263 J.Govers@BIOCH.unimaas.nl|
|Principal Investigator: Joke Konings, MSc|
|Principal Investigator:||Hugo Ten Cate, MD, PhD||Maastricht University Medical Centre|