In vitro COagulation Dynamics of conformational changes in ADAMTS13

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

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

Not applicable

One time blood draw