Blood-borne tissue factor (TF) has been shown to play a significant role in thrombosis, challenging the traditional view that TF is primarily present in the vascular wall and initiates coagulation upon vascular injury. This study demonstrates that TF can be present in circulating blood and is capable of initiating and propagating thrombosis. Using a system involving pig arterial media and collagen-coated glass slides perfused with native human blood, the researchers observed that thrombi formed on these surfaces were intensely stained for TF, much of which was not associated with cells. Anti-TF antibodies significantly reduced thrombus formation, indicating that TF from the blood contributes to thrombosis. TF deposited on the slides was active, leading to fibrin formation, and was inhibited by factor VIIa, a potent inhibitor of TF. Immunoelectron microscopy revealed TF-positive membrane vesicles near platelet surfaces, suggesting that leukocytes may be the main source of blood-borne TF. The study also identified TF-containing neutrophils and monocytes in peripheral blood, supporting the hypothesis that leukocytes are the primary source of TF in circulation. The findings suggest that blood-borne TF is inherently thrombogenic and may be involved in thrombus propagation at the site of vascular injury. The study provides evidence that circulating TF can initiate coagulation and that TF-positive cells in blood may contribute to thrombus formation. The results challenge the traditional view of TF's role in thrombosis and highlight the importance of blood-borne TF in the coagulation process.Blood-borne tissue factor (TF) has been shown to play a significant role in thrombosis, challenging the traditional view that TF is primarily present in the vascular wall and initiates coagulation upon vascular injury. This study demonstrates that TF can be present in circulating blood and is capable of initiating and propagating thrombosis. Using a system involving pig arterial media and collagen-coated glass slides perfused with native human blood, the researchers observed that thrombi formed on these surfaces were intensely stained for TF, much of which was not associated with cells. Anti-TF antibodies significantly reduced thrombus formation, indicating that TF from the blood contributes to thrombosis. TF deposited on the slides was active, leading to fibrin formation, and was inhibited by factor VIIa, a potent inhibitor of TF. Immunoelectron microscopy revealed TF-positive membrane vesicles near platelet surfaces, suggesting that leukocytes may be the main source of blood-borne TF. The study also identified TF-containing neutrophils and monocytes in peripheral blood, supporting the hypothesis that leukocytes are the primary source of TF in circulation. The findings suggest that blood-borne TF is inherently thrombogenic and may be involved in thrombus propagation at the site of vascular injury. The study provides evidence that circulating TF can initiate coagulation and that TF-positive cells in blood may contribute to thrombus formation. The results challenge the traditional view of TF's role in thrombosis and highlight the importance of blood-borne TF in the coagulation process.