Wolfram Ruf, M.D. presented “Tissue Factor Flip-Flopping Between Coagulation and Signaling” at Wednesday’s Plenary Session, providing a detailed assessment of the role of tissue factor (TF) in thrombotic, hemostatic, and immune pathways. He addressed how TF is involved in hemostasis and described the role that TF plays beyond hemostasis. Ruf then led participants through his detailed research findings, which also included the work of several of his colleagues:
- TF participates in host defense, hemostasis, and thrombosis in a context-dependent manner.
- TF’s hemostatic function is coordinated with receptor signaling networks that control the innate immune response to injury and infection and regulate regeneration and tissue repair.
- Deregulation of the TF pathway is central to thrombo-inflammation.
The role of tissue factor (TF) in thrombotic pathways was one focus of the presentation by Wolfram Ruf, M.D. at Wednesday’s Plenary Session. His research revealed that TF is released on extracellular prothrombic microvesicles and it is the main driver of prothrombic responses when cells are activated.
Ruf and colleagues are also interested in hemostatic pathways and have found that the tissue factor initiation complex of TF-factor VIIa generating FXa is a direct activator of FVIII. TF can directly trigger hemostatic responses in the absence of the thrombin feedback loop. This is important because understanding this concept will likely have implications for the safety of anticoagulant therapy and the new direct oral anticoagulants (DOACs), and will provide a ripe area for future study. In fact, the COMPASS (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS) trial is assessing rivaroxaban and the role that TF has in priming.
TF has important roles beyond hemostasis, particularly in immune response. Of particular interest is how cells behave in the intravascular spaces. He and his research team have examined how TF influences macrophage function. They found that FVII and FX play an active role in cell signaling pathways related to immune response. These interactions have implications for multiple disease states including breast cancer, and lung and skin inflammation as shown by Ruf’s colleagues. Ruf and colleagues are now looking at the potential translational applications of their current findings.