Saliva and urine from persons with hemophilia A trigger coagulation bypassing factor VIII

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.

Conflict of Interest

The authors have no competing conflicts of interest to declare.

Publikationsverlauf

Artikel online veröffentlicht:
20. Februar 2023