Thrombus Formation Under Different Flow-conditions

NCT ID: NCT01114074

Last Updated: 2016-09-13

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 46 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2017-04-30

Brief Summary

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.

Conditions

Thrombosis

Study Design

• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Factor XII deficiency

Patients deficient in coagulation factor XII

No interventions assigned to this group

Factor XI Deficiency

Patients deficient in coagulation factor XI

No interventions assigned to this group

Prekallikrein deficiency

Patients deficient in prekallikrein

No interventions assigned to this group

HMWK deficiency

Patients deficient in high molecular weight kininogen (HMWK)

No interventions assigned to this group

Control group

Healthy controls

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Patient group:
• Age: ≥ 18 years
• Deficiency in factor XII, factor XI, prekallikrein or high molecular weight kininogen
• Control group:
• Age: ≥ 18 years

Exclusion Criteria

• (Other) Coagulation defects
• Symptoms of active disease
• The use of antiplatelet drugs
• The use of aspirin/ascal

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Netherlands Heart Foundation

OTHER

Sponsor Role: collaborator

Maastricht University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hugo Ten Cate, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Maastricht University Medical Centre

Locations

Maastricht University

Maastricht, Limburg, Netherlands

Countries

Netherlands

Other Identifiers

#2008B120

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

10-3-015

Identifier Type: -

Identifier Source: org_study_id