Thrombus Formation Under Different Flow-conditions

NCT01114074 | Unknown

• 2 other identifiers: 10-3-015#2008B120
• Study Type: observational
• Target: 46
• Locations: 1 country
• Sites: 1

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

Keywords

Thrombosis; Blood coagulation; Perfusion flow experiments; Factor XII; Factor XI; Prekallikrein; High molecular weight kininogen

Outcome Measures

Primary Outcomes (1)

• Thrombus formation, stability and break down

  Using perfusion-flow experiments the formation, stability and break down of clots formed from the blood of the study participants will be determined.

  Up to 36 months

Study Arms (5)

Factor XII deficiency

Patients deficient in coagulation factor XII

Factor XI Deficiency

Patients deficient in coagulation factor XI

Prekallikrein deficiency

Patients deficient in prekallikrein

HMWK deficiency

Patients deficient in high molecular weight kininogen (HMWK)

Control group

Healthy controls

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients: Patients with a congenital factor XII-deficiency Patients with a congenital factor XI-deficiency Patients with a congenital prekallikrein-deficiency Patients with a congenital high molecular weight kininogen-deficiency Controls: Healthy individuals without any coagulation defects

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Netherlands Heart Foundation: collaborator

Study Sites (1)

Maastricht University

Maastricht, Limburg, 6229 ER, Netherlands

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

* Whole blood * Platelet poor plasma

MeSH Terms

Conditions

Thrombosis

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Hugo Ten Cate, MD, PhD

  Maastricht University Medical Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2010
• First Posted: April 30, 2010
• Study Start: May 1, 2011
• Primary Completion: December 1, 2016
• Study Completion: April 1, 2017
• Last Updated: September 13, 2016

Record last verified: 2016-09

Locations

NL (1)