Recent advances in treatments of adult immune thrombocytopenia

Kim, Dae Sik

doi:10.5045/br.2022.2022038

Cited by 8 publications

(5 citation statements)

References 71 publications

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“…Categorized based on the antigenic target site, these antibodies include various types such as anti-GPIa/IIa, anti-GPIbα, anti-GPIb/IX, and anti-GPIIb/IIIa antibodies ( 53 , 54 ). In the majority of ITP patients, anti-GPIIb/IIIa antibodies are present in 70% to 80% of cases, while anti-GPIbα antibodies are found in 20% to 40% of cases.…”

Section: The Process Of Generation Of Platelet Desialylationmentioning

confidence: 99%

The role of platelet desialylation as a biomarker in primary immune thrombocytopenia: mechanisms and therapeutic perspectives

Zhang,

Huang,

Thomas

et al. 2024

Front. Immunol.

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Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by the destruction of platelets. Although it was long believed that the critical role of autoantibodies in platelet destruction, primarily through the Fc-dependent platelet clearance pathway, recent findings indicate that the significance of the Fc-independent platelet clearance pathway mediated by hepatocytes, thus shedding light on a previously obscure aspect of ITP pathogenesis. Within this context, the desialylation of platelets has emerged as a pivotal biochemical marker. Consequently, targeting platelet desialylation emerges as a novel therapeutic strategy in the pathogenesis of ITP. Notably, prevailing research has largely focused on antiplatelet antibodies and the glycosylation-associated mechanisms of platelet clearance, while comprehensive analysis of platelet desialylation remains scant. In response, we retrospectively discuss the historical progression, inducing factors, generation process, and molecular regulatory mechanisms underlying platelet desialylation in ITP pathogenesis. By systematically evaluating the most recent research findings, we contribute to a comprehensive understanding of the intricate processes involved. Moreover, our manuscript delves into the potential application of desialylation regulatory strategies in ITP therapy, heralding novel therapeutic avenues. In conclusion, this manuscript not only fills a critical void in existing literature but also paves the way for future research by establishing a systematic theoretical framework. By inspiring new research ideas and offering insights into the development of new therapeutic strategies and targeted drugs, our study is poised to significantly advance the clinical management of ITP.

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Section: The Process Of Generation Of Platelet Desialylationmentioning

confidence: 99%

The role of platelet desialylation as a biomarker in primary immune thrombocytopenia: mechanisms and therapeutic perspectives

Zhang,

Huang,

Thomas

et al. 2024

Front. Immunol.

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“…2 EP, ROMI, and avatrombopag are currently approved for the treatment of persistent or chronic ITP, unresponsive to previous first-line agents or splenectomy. 9 Several studies have reported overall response rates of 60 to 90% in ITP patients receiving TPO-RAs. 9 Results of increased efficacy in ITP patients along with understanding TPO's effects on HSCs gave rise to employment of TPO-RAs in a variety of thrombocytopenic settings.…”

Section: Introductionmentioning

confidence: 99%

“…9 Several studies have reported overall response rates of 60 to 90% in ITP patients receiving TPO-RAs. 9 Results of increased efficacy in ITP patients along with understanding TPO's effects on HSCs gave rise to employment of TPO-RAs in a variety of thrombocytopenic settings. 2 EP has been shown effective in the management of thrombocytopenia related to hepatitis C virus (HCV) infection, thus allowing initiation and maintenance of interferon-based therapy.…”

Section: Introductionmentioning

confidence: 99%

Novel Perspectives on Thrombopoietin Receptor Agonists Applications

Stafylidis,

Vlachopoulou,

Syriopoulou

et al. 2024

Hamostaseologie

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Second-generation thrombopoietin receptor agonists (TPO-RAs), romiplostim, eltrombopag, and avatrombopag, have been proved to be significant stimulators of megakaryopoiesis and, in the last decade, they have been incorporated in the treatment options against refractory immune thrombocytopenia in children and adults that do not respond to conventional therapy. Additionally, given their beneficial impact on hematopoiesis, they have successfully been applied in cases of non-immune thrombocytopenia, such as aplastic anemia, HCV-related thrombocytopenia, chronic liver disease, and most recently acute radiation syndrome. During the past years, a wide variety of clinical studies have been performed, in regard to the use of TPO-RAs in various thrombocytopenic settings, such as malignant hematology and hematopoietic stem cell transplantation, hereditary thrombocytopenias, and chemotherapy-treated patients with solid organ tumors. Although data indicate that TPO-RAs may be an effective and safe option for managing disease- or treatment-related thrombocytopenia in these patients, further research is needed to determine their efficacy and safety in these settings. Furthermore, recent studies have highlighted novel properties of TPO-RAs that render them as potential treatment candidates for reducing tumor burden or fighting infections. Herein, we discuss the potential novel applications of TPO-RAs and focus on data regarding their efficacy and safety in these contexts.

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“…Thrombopoietin receptor agonists (TPO-RAs) are second-line drugs used to treat ITP. They can bind to and activate thrombopoietin receptors on the membranes of megakaryocytes in the bone marrow, thus promoting megakaryocyte maturation and increasing platelet production ( 4 , 5 ). Currently, TPO-RAs that have been approved by China, the US and the EU for the clinical treatment of ITP include romiplostim, eltrombopag, avatrombopag and hetrombopag ( 5 , 6 ).…”

Section: Introductionmentioning

confidence: 99%

“…They can bind to and activate thrombopoietin receptors on the membranes of megakaryocytes in the bone marrow, thus promoting megakaryocyte maturation and increasing platelet production (4,5). Currently, TPO-RAs that have been approved by China, the US and the EU for the clinical treatment of ITP include romiplostim, eltrombopag, avatrombopag and hetrombopag (5,6). Over the Thrombopoietin receptor agonists use and risk of thrombotic events in patients with immune thrombocytopenic purpura: A systematic review and meta-analysis of randomized controlled trials past decade, TPO-RAs have become increasingly common for treating ITP.…”

Section: Introductionmentioning

confidence: 99%

Thrombopoietin receptor agonists use and risk of thrombotic events in patients with immune thrombocytopenic purpura: A systematic review and meta‑analysis of randomized controlled trials

Shen,

Qiao,

Jiang

et al. 2024

Biomed Rep

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Thrombopoietin receptor agonists (TPO-RAs) have a role in second-line immune thrombocytopenic purpura (ITP) treatment, binding to and activating thrombopoietin receptors on megakaryocyte membranes in the bone marrow. This promotes megakaryocyte maturation and increases platelet production. Despite a 2-6% incidence of thrombotic events during TPO-RA treatment, it remains uncertain whether TPO-RAs elevate thrombosis rates. A comprehensive search of electronic databases was conducted using the relevant search criteria. To assess the risk of bias, the included studies were assessed using the revised Cochrane Risk of Bias Assessment Tool 2.0, and a meta-analysis was performed using RevMan 5.4.1. A total of 1,698 patients with ITP were included from randomized controlled trials (RCTs). There were 26 thromboembolic events in the TPO-RAs group and 4 in the control group. However, there was no significant difference in the incidence of thrombotic events between the two groups [odds ratio (OR)=1.76, 95% confidence interval (CI): 0.78-4.00, P=0.18], even if the duration of treatment was >12 weeks (OR=2.46, 95% CI: 0.81-7.43, P=0.11). Subgroup analysis showed that none of the four drugs significantly increased the incidence of thrombotic events (romiplostim: OR=0.92, 95% CI: 0.14-6.13, P=0.93; eltrombopag: OR=2.32, 95% CI: 0.64-8.47, P=0.20; avatrombopag: OR=4.15, 95% CI: 0.20-85.23, P=0.36; and hetrombopag: OR=0.76, 95% CI: 0.03-18.76, P=0.87). There was also no significant difference in the results of the double-blinded placebo-controlled RCTs (OR=1.21, 95% CI: 0.41-3.58, P=0.73). Compared to patients with ITP who did not receive TPO-RA treatment, those receiving TPO-RA treatment did not exhibit a significantly increased risk of thrombotic events.

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Recent advances in treatments of adult immune thrombocytopenia

Cited by 8 publications

References 71 publications

The role of platelet desialylation as a biomarker in primary immune thrombocytopenia: mechanisms and therapeutic perspectives

The role of platelet desialylation as a biomarker in primary immune thrombocytopenia: mechanisms and therapeutic perspectives

Novel Perspectives on Thrombopoietin Receptor Agonists Applications

Thrombopoietin receptor agonists use and risk of thrombotic events in patients with immune thrombocytopenic purpura: A systematic review and meta‑analysis of randomized controlled trials

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