Under Blood Flow Conditions

A human ex vivo thrombosis model was used to investigate whether recombinant annexin V (rANV) can prevent thrombus formation under venous and arterial blood flow conditions. In this model, blood from an antecubital vein of healthy donors was allowed to flow directly over the extracellular matrix of tumor necrosis factor-stimulated endothelial cells (TNF-ECMs). TNF-ECMs were preincubated with rANV (2.9 /imol/L) for 30 minutes. With this rANV concentration all binding sites present on TNF-ECMs (1.6±0.5 x 10/ cm) are occupied, and a maximal inhibition was observed in a tissue factor-dependent clotting assay. Fibrin deposition and platelet and leukocyte adhesion were measured on the rANVtreated and nontreated TNF-ECMs. Nontreated TNF-ECMs Subendothelial structures become exposed to the circulating blood through damage of the vessel wall. Exposed subendothelium is highly thrombogenic because tissue factor and proteins adhesive for platelets are present. Ryan et al report that tissue factor is associated with phospholipid vesicles in tumor necrosis factor-stimulated endothelial cell matrices