No registrations found.
ID
Source
Brief title
Health condition
None
Sponsors and support
Intervention
Outcome measures
Primary outcome
ROTEM lysis, EXTEM/FIBTEM/ABTEM (i.e. LT, LOT, Li (t), ML, CLR), measured on the day of the blood draw
Secondary outcome
ADAMTS13 plasma determinations (antigen, activity, conformation, degradation)
Plasma turbidity (time to onset, slope, degree)
Whole blood clot lysis, using HALO assay (time to onset, slope, degree),
Platelet activation (CD62P, PAC1), using flow cytometry
Platelet adhesion and aggregation, using flow model (Time to platelet adhesion, aggregation and breakdown of clots, measured using fluorescent live-cell imaging).
*There will be only one blood draw (and thus one timepoint) for the volunteer. All outcomes except the ADAMTS plasma determinations. will be measured on the day of thid blood draw. The ADAMTS13 plasma determinations will be performed on a later moment on frozen plasma obtained from the inital blood draw.
Background summary
Rationale:
Severely injured trauma patients present in 40% of cases with a trauma-induced coagulopathy, composed of severe platelet dysfunction, coagulation factor consumption and hyperfibrino(geno)lysis. ADAMTS13 is a cleaving enzyme of von Willebrand factor. Its role in coagulation during hyperfibrino(geno)lysis is poorly understood. Our hypothesis is that ADAMTS13 changes its conformation when it is cleaved by plasmin. This study on coagulation effects of conformation changes of ADAMTS13 will be performed in vitro after drawing blood from healthy volunteers.
Objectives:
1. To identify the role of conformational changes of ADAMTS13 in in vitro coagulation tests and flow models
2. To identify the role of plasmin on ADAMTS13 conformation on in vitro coagulation tests
Study design: healthy volunteer observational study
Study population: healthy human male volunteers, 18 - 35 yr old, n=24
Intervention (if applicable): Blood draw (1x)
Main study parameters/endpoints:
End-points are all measured in vitro using the whole blood obtained from healthy volunteers.
1. Amount of hyperfibrino(geno)lysis, conformation status of ADAMTS13, coagulation proteins, platelet surface markers and additionally in flow models endothelial activation markers
Study objective
tPA-induced lysis leads to cleaved ADAMTS13:
a. accelerating fibrin(ogen) breakdown in in vitro coagulation assays
b. leading to impaired platelet adhesion and aggregation in an in vitro flow model
Study design
Not applicable
Intervention
One time blood draw
Inclusion criteria
- Male
- Age 18-35
Exclusion criteria
- Participation in a scientific intervention study in the last 3 months
- No informed consent
- History of coagulation disorders
- Active use of prescription medication
- Use of anticoagulant medication, including aspirin
- History of liver disease
- History of chronic transmittable disease
- History of alcohol, smoking or drug abuse
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL9193 |
| Other | METC AMC : METC 2020_171 |