Influence of endothelial cells on coagulation and fibrinolysis measured by thromboelastography

Thromboelastography (TEG) is used to assess hemostasis in whole blood1. It is a
dynamic test depicting the initiating, the structural characteristics and
stability of the formed clot. Routine laboratory tests are, in contrast to TEG,
performed on plasma only and provide no information about interactions of blood
cells, pro- and anticoagulants, and pro- and antifibrinolytic factors,
essential in the clotting process.
However, the TEG test results do not cover all elements involved in
hemostasis. Endothelial cells (EC) form the luminal vascular surface play a
central role in the regulation of coagulation and fibrinolysis.
In coagulation EC regulates binding sites for anti- and procoagulant factors
on the cell surface. EC maintain the blood fluidity by promoting anticoagulant
pathways including the protein C/S pathway. Tumor necrosis factor (TNF)
suppresses thrombomodulin binding on EC and induces expression of tissue factor
resulting in a state to favour clot formation.
In fibrinolysis EC express both types of plasminogen activators, the
urokinase-type PA and the the tissue-type plasminogen activator, as well as
their inhibitor plasminogen activator inhibitor type (PAI-I). Stimulation or
inhibition of these activators may result in a hypo- or hyper- fibrinolysis.

Test results of the TEG are missing the important influence of the endothelial
cells simply because the test is performed in a plastic cup without an
endothelial layer. This shortcoming may be resolved by introducing endothelial
cells in the TEG test-cup.

Human Umbilical vein endothelial Cells (HUVEC) are isolated from human
umbilical vein. These cells are commonly used for physiological and
pharmacological investigations including blood coagulation2 and fibrinolysis3.
It is possible in the laboratory of the UMCG (endotheelcel & vasculaire drug
targering) to cover the TEG-cups with HUVEC. This technique has not been
described in the literature and hence, the effect of EC-coated TEG-cups
compared to the plain TEG-cups on hemostasis has not been studied before.

The purpose of the study is to investigate the effect of endothelial cells in
TEG-cups compared to plain (no endothelial cells) cups on coagulation and
fibrinolysis.

clinical observational mono-center study

From healthy volunteers 5 ml of venous blood is collected. It is unlikely that
subjects will experience any physical or psychological discomfort from this
blood sampling.