HE PATHOGENESIS of coronary and cerebrovascular T thrombosis has been traditionally interpreted as a

“misdirected” form of hemostasis in which platelets interact with subendothelium, leading to adhesion, activation, aggregation, and recruitment, accompanied by fibrin formation. This concept evolved mainly from studies of the response of healthy blood vessels to physical injury and formed the basis for current platelet-directed therapeutic approaches to arterial thrombosis. However, thrombotic events almost always occur at sites of pathologic vascular damage, containing lipid-rich or necrotic tissue and inflammatory Disturbed blood flow at these sites promotes interactions between multiple cell types.

Time course studies of the morphology of an evolving thrombus always show participation of several cell types, in addition to the normal endothelial cells surrounding the lesion. Platelets form the central core of the thrombus, which then becomes admixed with erythrocytes, neutrophils, and later monocytes. Physical participation of multiple cells was initially thought to be passive. However, our in vitro studies involving reactions of endothelial cells, erythrocytes, and neutrophils with platelets led us to consider thrombosis as an integrated group of multicellular events. Cell contact and varying degrees of pathologic stimulation govern development and reversibility of thrombosis. We hypothesize that thrombotic and inflammatory responses are biochemically linked as part of overall mechanisms of host defense. The physical and biologic behavior of one cell can be markedly altered by the presence of another. This result can be due to direct cell contact or to secretory products of one or more cell types, especially after activation by specific agonist (^).^-'There are at least two major issues confronting current approaches to the pathogenesis and treatment of thrombosis:(1) Will therapy directed against a single cell type or thrombus component be satisfactory on a long term basis?(2) Can control of newly recognized thromboregulators acting at the vessel interface form the basis for more definitive therapeusis?