Spontaneous Platelet Aggregation in Blood Is Mediated by FcRIIA Stimulation of Bruton's Tyrosine Kinase
Research article published in International journal of molecular sciences (2021)
Abstract
High platelet reactivity leading to spontaneous platelet aggregation (SPA) is a hallmark of cardiovascular diseases; however, the mechanism underlying SPA remains obscure. Platelet aggregation in stirred hirudin-anticoagulated blood was measured by multiple electrode aggregometry (MEA) for 10 min. SPA started after a delay of 2-3 min. In our cohort of healthy blood donors (n = 118), nine donors (8%) with high SPA (>250 AU*min) were detected. Pre-incubation of blood with two different antibodies against the platelet Fc-receptor (anti-FcγRIIA, CD32a) significantly reduced high SPA by 86%. High but not normal SPA was dose-dependently and significantly reduced by blocking Fc of human IgG with a specific antibody. SPA was completely abrogated by blood pre-incubation with the reversible Btk-inhibitor (BTKi) fenebrutinib (50 nM), and 3 h after intake of the irreversible BTKi ibrutinib (280 mg) by healthy volunteers. Increased SPA was associated with higher platelet GPVI reactivity. Anti-platelet factor 4 (PF4)/polyanion IgG complexes were excluded as activators of the platelet Fc-receptor. Our results indicate that high SPA in blood is due to platelet FcγRIIA stimulation by unidentified IgG complexes and mediated by Btk activation. The relevance of our findings for SPA as possible risk factor of cardiovascular diseases and pathogenic factor contributing to certain autoimmune diseases is discussed.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
High platelet reactivity leading to spontaneous platelet aggregation (SPA) is a hallmark of cardiovascular diseases; however, the mechanism underlying SPA remains obscure.
Por qué esto importa para la hirudoterapia
Este estudio investigó el mecanismo de la agregación plaquetaria espontánea (SPA) en sangre anticoagulada con hirudina procedente de 118 donantes sanos, medida mediante agregometría de electrodos múltiples. Los autores encontraron que la SPA elevada (>250 AU*min), presente en el 8 % de los donantes, se redujo significativamente con anticuerpos bloqueantes del receptor plaquetario FcγRIIA y fue completamente abolida por inhibidores de la tirosina quinasa de Bruton (fenebrutinib in vitro; ibrutinib in vivo). La hirudina sirvió como anticoagulante para la recolección de sangre en este ensayo, lo que la hace relevante para ASH como aplicación de laboratorio de un anticoagulante derivado de la sanguijuela en la investigación de la función plaquetaria. Sin embargo, el foco del estudio es la biología de la señalización plaquetaria, no la hirudoterapia ni el uso terapéutico del secretoma de la sanguijuela; la hirudina se emplea únicamente como reactivo, y no se involucran sanguijuelas ni aplicaciones terapéuticas.
Citación
Spontaneous Platelet Aggregation in Blood Is Mediated by FcRIIA Stimulation of Bruton's Tyrosine Kinase
Duan R et al. · International journal of molecular sciences, 2021
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026