Clinical trial NCT01114074: Thrombus Formation Under Different Flow-conditions
Official title: The Influence of the Proteins of the Contact Activation System on Thrombus Formation Under Different Flow-conditions in Blood
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Thrombosis
Keywords: Thrombosis
Blood coagulation
Perfusion flow experiments
Factor XII
Factor XI
Prekallikrein
High molecular weight kininogen
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: Netherlands Heart Foundation
First posted: 2010-04-30
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Time perspective: CROSS_SECTIONAL
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

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.


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

Primary outcomes:
measure: Thrombus formation, stability and break down
timeFrame: Up to 36 months
Secondary outcomes:
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University
state: Limburg
Study officials:
affiliation: Maastricht University Medical Centre
name: Hugo Ten Cate, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: