Blood-borne tissue factor: Another view of thrombosis

Arterial thrombosis is considered to arise from the interaction of tissue f actor (TF) in the vascular wall with platelets and coagulation factors in c irculating blood. According to this paradigm, coagulation is initiated afte r a vessel is damaged and blood is exposed to vessel-wall TF, We have exami ned thrombus formation on pig arterial media (which contains no stainable T F) and on collagen-coated glass slides (which are devoid of TF) exposed to flowing native human blood. In both systems the thrombi that formed during a 5-min perfusion stained intensely for TF, much of which was not associate d with cells. Antibodies against TF caused approximate to 70% reduction in the amount of thrombus formed on the pig arterial media and also reduced th rombi on the collagen-coated glass slides. TF deposited on the slides was a ctive, as there was abundant fibrin in the thrombi, Factor VIIal, a potent inhibitor of TF, essentially abolished fibrin production and markedly reduc ed the mass of the thrombi, Immunoelectron microscopy revealed TF-positive membrane vesicles that we frequently observed in large clusters near the su rface of platelets. TF, measured by factor X-a formation, was extracted fro m whole blood and plasma of healthy subjects. By using immunostaining, TF-c ontaining neutrophils and monocytes were identified in peripheral blood; ou r data raise the possibility that leukocytes are the main source of blood T F, We suggest that blood-borne TF is inherently thrombogenic and may be inv olved in thrombus propagation at the site of vascular injury.