English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

The multidrug resistance protein-4 (MRP4), an ATPbinding cassette transporter, is involved in the efflux of several pharmacological and physiological compounds. MRP4 plays a role in modulating platelet function and influences platelet activation. It has been identified as a modulator of the action of acetylsalicylic acid (ASA) in platelets. A high on-ASA residual platelet reactivity (HARPR) has been found in patients with MRP4 overexpression. Furthermore, MRP4 overexpression induced by drugs mediates a hyperreactive platelet phenotype. Recent studies have demonstrated that ASA also modulates various microRNA and gene expression, such as that of PPARα, resulting in platelet MRP4 overexpression. MRP4 knockout mice have reduced platelet function, delayed arterial thrombosis and prolonged bleeding time. In patients who had undergone a surgical bypass procedure, MRP4 overexpression was found to have a role in reducing the effect of ASA and, at the same time, ASA induced platelet MRP4 upregulation. In most patients with essential thrombocythemia (ET), ASA has been reported to incompletely inhibit platelet thromboxane A2. Based on our experience, we suggested that the subtypes of primary thrombocythemia (PT) in children are different from those found in adults with ET: 40% had JAK2(V617F) or CALR-mutated ET, 36% had a MPL(S505A) mutation and received a diagnosis of hereditary thrombocytosis (HT), while 24% had JAK2, CALR and MPL wildtype ET. Moreover, thrombotic events, frequent in adult ET and rare in pediatric PT, have been observed in HT children with the MPL(S505A) mutation during treatment with ASA. This study was designed to evaluate and correlate MRP4 expression and platelet function in children and adolescents aged <20 years at diagnosis with different subtypes of PT. MRP4 protein and platelet aggregation were evaluated in 30 healthy volunteers (HV) and in 41 PT patients (males: 18; females 23; median age at diagnosis: 14.5 years; range: 3 months-20 years). Of the 41 PT patients, 10 had the JAK2(V617F) mutation, 6 harbored CALR mutations, 10 carried a MPL(S505A) mutation and 15 were JAK2, CALR and MPL wildtype. Patients were grouped as follows: patients with JAK2(V617F) and CALR mutations (n=16); patients who had JAK2, CALR and MPL wildtype genes, defined as having triple-negative ET(n=15); patients with a MPL(S505A) mutation,

Platelet activation and multidrug resistance protein-4 expression in children and adolescents with different subtypes of primary thrombocythemia