Novel Knowledge about Molecular Mechanisms of Heparin-Induced Thrombocytopenia Type II and Treatment Targets
Research article published in International journal of molecular sciences (2023)
Abstract
Heparin-induced thrombocytopenia type II (HIT II), as stated in the literature, occurs in about 3% of all patients and in 0.1-5% of surgical patients. Thrombosis develops in 20-64% of patients with HIT. The mortality rate in HIT II has not decreased using non-heparin treatment with anticoagulants such as argatroban and lepirudin. An improved understanding of the pathophysiology of HIT may help identify targeted therapies to prevent thrombosis without subjecting patients to the risk of intense anticoagulation. The review will summarize the current knowledge about the pathogenesis of HIT II, potential new therapeutic targets related to it, and new treatments being developed. HIT II pathogenesis involves multi-step immune-mediated pathways dependent on the ratio of PF4/heparin and platelet, monocyte, neutrophil, and endothelium activation. For years, only platelets were known to take part in HIT II development. A few years ago, specific receptors and signal-induced pathways in monocytes, neutrophils and endothelium were revealed. It had been shown that the cells that had become active realised different newly formed compounds (platelet-released TF, TNFα, NAP2, CXCL-7, ENA-78, platelet-derived microparticles; monocytes-TF-MPs; neutrophils-NETs), leading to additional cell activation and consequently thrombin generation, resulting in thrombosis. Knowledge about FcγIIa receptors on platelets, monocytes, neutrophils and FcγIIIa on endothelium, chemokine (CXCR-2), and PSGL-1 receptors on neutrophils could allow for the development of a new non-anticoagulant treatment for HIT II. IgG degradation, Syk kinase and NETosis inhibition are in the field of developing new treatment possibilities too. Accordingly, IdeS and DNases-related pathways should be investigated for better understanding of HIT pathogenesis and the possibilities of being the HIT II treatment targets.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Novel Knowledge about Molecular Mechanisms of Heparin-Induced Thrombocytopenia Type II and Treatment Targets.
Por qué esto importa para la hirudoterapia
Esta revisión resume el conocimiento actual sobre la patogénesis de la trombocitopenia inducida por heparina tipo II (HIT II) y las dianas terapéuticas emergentes, e informa que la HIT II se presenta en aproximadamente el 3% de todos los pacientes y que la trombosis se desarrolla en el 20–64% de los pacientes afectados. Cabe destacar, para la ASH, que los autores observan que la mortalidad por HIT II no ha disminuido a pesar del tratamiento con anticoagulantes no heparínicos, entre ellos la lepirudina —una forma recombinante de la hirudina derivada originalmente del secretoma de la sanguijuela medicinal—, lo que subraya tanto el papel establecido de los anticoagulantes derivados de la sanguijuela en el manejo de esta grave complicación trombótica como las limitaciones, incluso, de la terapia basada en hirudina. La revisión describe mecanismos inmunomediados de múltiples pasos que involucran plaquetas, monocitos, neutrófilos y endotelio, y discute posibles dianas no anticoagulantes tales como los receptores Fcγ, la quinasa Syk y las vías de NETosis. Sin embargo, se trata de una revisión narrativa que sintetiza la literatura existente en lugar de investigación original, y sus observaciones sobre los desenlaces con lepirudina reflejan estudios previos acumulados en lugar de nuevos datos de ensayos.
Citación
Novel Knowledge about Molecular Mechanisms of Heparin-Induced Thrombocytopenia Type II and Treatment Targets
Mongirdiene A et al. · International journal of molecular sciences, 2023
Contexto clínico relacionado
Explore cómo esta investigación se conecta con la práctica clínica
Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026