AI Article Synopsis
- Human saliva contains extracellular vesicles (EVs) that can activate blood coagulation through the presence of extrinsic tenase complexes, which include tissue factor and activated factor VII.
- Individuals with severe hemophilia A, who lack FVIII, have salivary EVs that can compensate for their condition by generating FXa, leading to infrequent oropharyngeal bleeding.
- In contrast, people with severe FVII deficiency lack these functional extrinsic tenase complexes in their saliva, resulting in more frequent oropharyngeal bleedings; however, adding recombinant FVIIa can restore coagulation potential in their saliva.
Article Abstract
Human saliva contains extracellular vesicles (EVs). These EVs expose extrinsic tenase complexes of tissue factor (TF) and activated factor VII (FVIIa), and trigger blood coagulation. Here, we show that EVs exposing extrinsic tenase complexes are also present in saliva of persons with severe hemophilia A, that is, persons with FVIII deficiency. Addition of these salivary EVs to autologous FVIII-deficient blood results in FXa generation, thereby compensating for the lack of FXa generation via intrinsic tenase (FVIIIa/FIXa) complexes. Consistently, in our retrospective analysis of persons with severe hemophilia A who do not receive prophylactic FVIII substitution, oropharyngeal mucosal bleedings are infrequent and self-limited. Conversely, in saliva of persons with severe FVII deficiency, in whom oropharyngeal bleedings are prevalent, functional extrinsic tenase complexes are absent, because EVs lack FVII. Saliva of persons with severe FVII deficiency is unable to restore blood coagulation, which is because of the absence of FVII in both their saliva and blood. Picomolar levels of recombinant FVIIa can restore the coagulant potential of saliva of persons with FVII deficiency. Taken together, our findings may explain the paucity of oropharyngeal bleedings in persons with hemophilia A as well as the occurrence of such bleedings in persons with severe FVII deficiency.
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| http://dx.doi.org/10.1182/blood.2024025093 | DOI Listing |
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