28 Jun Extracellular vesicles from amniotic fluid, milk, saliva, and urine expose complexes of tissue factor and activated factor VII
Abstract
Background
Tissue factor (TF) is expressed in the adventitia of the vessel wall and also commonly present on extracellular vesicles (EVs) in normal body fluids. TF and activated coagulation factor (F) VII(a) together form the so-called extrinsic tenase complex, which initiates coagulation.
Aim
We investigated whether EVs in amniotic fluid, milk, saliva, and urine expose functional extrinsic tenase complexes that can trigger coagulation.
Methods
Milk, saliva, and urine were collected from healthy breastfeeding women (n=6), and amniotic fluid was collected from healthy women undergoing routine amniocentesis (n=7). Extracellular vesicles (EVs) were isolated from body fluids by size exclusion chromatography (SEC) and clotting experiments were performed in the presence and absence of antibodies against TF and FVIIa in normal plasma and in FVII-deficient plasma. Also the ability of body fluids to generate FXa was determined.
Results
Amniotic fluid, milk, saliva, and urine triggered clotting of normal plasma and of FVII-deficient plasma, which was almost completely inhibited by anti-FVII and to a lesser extend by anti-TF. Fractionation of body fluids by SEC showed that only the fractions containing EVs triggered clotting in normal plasma and FVII-deficient plasma and generated FXa, which again was almost completely inhibited by anti-FVII and partially by anti-TF.
Conclusion
Here we show that EVs from amniotic fluid, milk, saliva, and urine expose complexes of TF and FVIIa (i.e. extrinsic tenase complexes) that directly activate FX. Based on our present findings we propose that these EVs from normal body fluids provide hemostatic protection.