DESMOPRESSIN (DDAVP) ENHANCES PLATELET-ADHESION TO THE EXTRACELLULAR-MATRIX OF CULTURED HUMAN ENDOTHELIAL-CELLS THROUGH INCREASED EXPRESSION OF TISSUE FACTOR

The effect of desmopressin (DDAVP) on thrombogenicity, expression of t issue factor and procoagulant activity (PCA) of extracellular matrix ( ECM) generated by human umbilical vein endothelial cells cultures (HUV EC), was studied under different experimental conditions. HUVEC were i ncubated with DDAVP (1, 5 and 30 ng/ml) and then detached from their E CM. The reactivity towards platelets of this ECM was tested in a perfu sion system. Coverslips covered with DDAVP-treated ECMs were inserted in a parallel-plate chamber and exposed to normal blood anticoagulated with low molecular weight heparin (Fragmin(R), 20 U/ml). Perfusions w ere run for 5 min at a shear rate of 800 s(-1). Deposition of platelet s on ECMs was significantly increased with respect to control ECMs whe n DDAVP was used at 5 and 30 ng/ml (p < 0.05 and p < 0.01 respectively ). The increase in platelet deposition was prevented by incubation of ECMs with an antibody against human tissue factor prior to perfusion. Immunofluorescence studies positively detected tissue factor antigen o n DDAVP derived ECMs. A chromogenic assay performed under standardized conditions revealed a statistically significant increase in the proco agulant activity of the ECMs produced by ECs incubated with 30 ng/ml D DAVP (p < 0.01 vs. control samples). Northern blot analysis revealed i ncreased levels of tissue factor mRNA in extracts from ECs exposed to DDAVP. Our data indicate that DDAVP in vitro enhances platelet adhesio n to the ECMs through increased expression of tissue factor. A similar increase in the expression of tissue factor might contribute to the i n vivo hemostatic effect of DDAVP.