Ultrastructural observations of an electron dense amorphous layer on selectively damaged endothelial cells, a possible trigger of thrombogenesis in vivo, and its inhibition by nafazatrom.

Platelet aggregation can be induced by intravascular excitation of fluoresceinisothiocyanate-dextran. Cheek pouches of untreated hamsters and of nafazatrom recipients were excised before and after exposure to the exciting light for 1, 4, 6, 10 and 25 minutes and examined electron microscopically. The first observable ultrastructural change was a swelling of endothelial cells. Polymorphonuclear leukocytes began to transmigrate into the interstitium. After 4 minutes, amorphous, optically dense substances appeared on endothelial surfaces. Only on these which platelets later became adherent. Thrombi grew until vessels were occluded. The thrombi were formed by the amorphous structure, degranulated platelets and unaffected red blood cells and leukocytes. No fibrin strands were observed. Pretreatment with 100 micrograms/kg b.w. nafazatrom, a potent antithrombotic agent which stimulates endothelial release of prostacyclin, totally abolished the occurrence of the observed amorphous epiendothelial structure as well as the occurrence of platelet thrombi.