Intravascular tissue factor initiates coagulation via circulating microvesicles and platelets.

Area of Science:

• Hematology
• Cell Biology
• Thrombosis Research

Background:

• Tissue Factor (TF) initiates coagulation and thrombosis.
• Intravascular TF's functional significance and location remain unclear.
• Previous studies suggested TF presence in human blood.

Purpose of the Study:

• To determine the location and functional significance of intravascular TF.
• To investigate the role of microvesicles and platelets in TF-associated coagulation.
• To elucidate the mechanisms enabling TF activity in blood.

Main Methods:

• Utilized cell sorting with CD42b marker to identify TF-bearing microvesicles.
• Analyzed TF localization in resting and activated platelets.
• Investigated TF functional competence through interactions with neutrophils.

Main Results:

• TF is primarily associated with circulating microvesicles in plasma.
• Platelet-derived microvesicles are a major source of plasma TF.
• TF is stored in platelet alpha-granules and exposed upon activation.
• Neutrophil adhesion to platelets/microvesicles, mediated by P-selectin/PSGL-1, enables TF activity.
• Neutrophil-secreted oxygen radicals enhance TF activity.
• Platelet and microvesicle TF contribute equally to blood TF activity.

Conclusions:

• Introduces a new concept of TF-mediated coagulation.
• Coagulation critically depends on TF associated with microvesicles and activated platelets.
• TF on microvesicles and platelets enables coagulation on restricted cell surfaces.