Coagulation Factor XIIIa and Activated Protein C Activate Platelets via GPVI and PAR1
Research article published in International journal of molecular sciences (2022)
Abstract
Platelet and coagulation activation are highly reciprocal processes driven by multi-molecular interactions. Activated platelets secrete several coagulation factors and expose phosphatidylserine, which supports the activation of coagulation factor proteins. On the other hand, the coagulation cascade generates known ligands for platelet receptors, such as thrombin and fibrin. Coagulation factor (F)Xa, (F)XIIIa and activated protein C (APC) can also bind to platelets, but the functional consequences are unclear. Here, we investigated the effects of the activated (anti)coagulation factors on platelets, other than thrombin. Multicolor flow cytometry and aggregation experiments revealed that the 'supernatant of (hirudin-treated) coagulated plasma' (SCP) enhanced CRP-XL-induced platelet responses, i.e., integrin αIIbβ3 activation, P-selectin exposure and aggregate formation. We demonstrated that FXIIIa in combination with APC enhanced platelet activation in solution, and separately immobilized FXIIIa and APC resulted in platelet spreading. Platelet activation by FXIIIa was inhibited by molecular blockade of glycoprotein VI (GPVI) or Syk kinase. In contrast, platelet spreading on immobilized APC was inhibited by PAR1 blockade. Immobilized, but not soluble, FXIIIa and APC also enhanced in vitro adhesion and aggregation under flow. In conclusion, in coagulation, factors other than thrombin or fibrin can induce platelet activation via GPVI and PAR receptors.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Platelet and coagulation activation are highly reciprocal processes driven by multi-molecular interactions.
Por qué esto importa para la hirudoterapia
Este estudio in vitro investigó si factores de coagulación distintos de la trombina —específicamente el Factor XIIIa y la proteína C activada (PCA)— pueden activar plaquetas a través de los receptores GPVI y PAR1, utilizando sobrenadante de plasma coagulado tratado con hirudina como parte de la preparación experimental. La hirudina se emplea aquí puramente como reactivo anticoagulante de laboratorio para eliminar la contribución de la trombina, lo que permite aislar los efectos de activación plaquetaria de otros factores. Los hallazgos profundizan en la comprensión de la interacción plaquetas-coagulación, que es precisamente el sistema que modulan anticoagulantes de sanguijuela como la hirudina. Sin embargo, el artículo no estudia la hirudoterapia ni el secretoma de la sanguijuela; simplemente emplea hirudina como herramienta, por lo que su relevancia para el ámbito de ASH es indirecta y mecanística más que terapéutica.
Citación
Coagulation Factor XIIIa and Activated Protein C Activate Platelets via GPVI and PAR1
De Simone I et al. · International journal of molecular sciences, 2022
Contexto clínico relacionado
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026