Introduction We previously demonstrated that saliva and urine from healthy individuals trigger
coagulation via tissue factor/activated factor VII (TF/FVIIa) complex exposing extracellular
vesicles (EVs). In persons with hemophilia A, saliva and urine may provide hemostatic
protection via TF/FVIIa complex exposing EVs.
Method Saliva, urine, and plasma were collected from 5 male persons with severe hemophilia
A before and after prophylactic administration of FVIII concentrates. For plasma clotting
experiments, saliva and urine were mixed with pooled normal plasma, autologous FVIII-deficient
plasma, and commercial FVII-deficient plasma.
Results Saliva and urine from persons with hemophilia A triggered clotting of pooled normal
plasma and of autologous FVIII deficient plasma ([Fig. 1]). The coagulant potential of saliva and urine did not change after intravenous administration
of FVIII concentrates ([Fig. 2a] and [2b]). Saliva and urine triggered clotting also in FVII-deficient plasma, which lacks
TF and FVII, and this coagulant potential was inhibited by antibodies against FVII
(clone 3G12) and TF (clone HTF-1) . The bulk of the coagulant potential of saliva
and urine was pelleted by differential centrifugation, confirming that the coagulant
activity is associated with EVs. Taken together, these findings confirmed the presence
of TF/FVIIa complex exposing EVs in saliva and urine from persons with hemophilia
A, which are able to trigger clotting in FVIII-deficient plasma.
Fig. 1
Fig. 2
Conclusion In FVIII-deficient plasma from persons with hemophilia A, saliva and urine act as
endogenous FVIII-bypassing agents that trigger clotting via TF/FVIIa complex exposing
EVs. Efficient FXa generation by saliva and urine seems to compensate for the lack
of intrinsic tenase complexes (i.e. FVIII/FIXa complexes) in persons with hemophilia
A. This may explain why persons with hemophilia A rarely develop mucosal bleedings.
