Thrombopoietin Receptor Research Articles

Immune thrombocytopenia in patients with systemic lupus erythematosus.

Immune thrombocytopenia (ITP) is a common hematological manifestation of systemic lupus erythematosus (SLE). The diversity of its clinical features and treatment responses may reveal the complex pathophysiological mechanisms of the disease. To enhance the therapeutic response rate and improve the prognosis for SLE patients with concurrent ITP, while reducing adverse events during the treatment process, it is crucial to accurately identify and apply clinical parameters to predict patients' responses to treatment. In addition to conventional therapeutic approaches such as glucocorticoids, immunosuppressants, and intravenous immunoglobulin (IVIG), a range of emerging therapies are gradually becoming the focus of research. These innovative therapeutic strategies include thrombopoietin receptor agonists (TPO-RAs), targeted therapies against B-cells, and plasma cell-targeted treatments. With a deepening understanding of the role of platelets in immune and inflammatory responses, novel platelet-targeted therapeutic agents in the field of SLE-ITP treatment may demonstrate significant potential. Despite this, to ensure the clinical efficacy and safety of these therapeutic approaches, we must rely on rigorously designed randomized controlled trials (RCTs) for further validation. This article provides a systematic review of the pathogenesis of systemic lupus erythematosus (SLE) complicated by immune thrombocytopenia (ITP) and conducts a comprehensive overview of current treatment strategies. The article also provides an in-depth exploration of the key biomarkers that may influence the therapeutic response in SLE-ITP patients. This comprehensive analysis aims to elucidate the factors that potentially affect the efficacy of treatments and contribute to a more personalized approach to patient care.

A study of platelet function in patients with chronic immune thrombocytopenia treated with thrombopoietin receptor agonists

BackgroundThrombopoietin receptor agonists (TPO-RAs) are widely used in immune thrombocytopenia (ITP) and are associated with increased thrombotic risk. However, data regarding their impact on platelet function is scarce. MethodsPlatelet function was evaluated in chronic ITP patients enrolled over one year, using light transmission aggregometry and platelet-derived microparticle (PMP) levels measurement with flow cytometry. Aggregation responses to various concentrations of ADP, collagen, ristocetin, and PMP levels were compared between TPO-RA-treated patients, patients treated with other agents and healthy individuals. ResultsTPO-RA-treated patients (n = 24) displayed significantly reduced aggregation responses to 2.5 μM, 5 μM, and 10 μM of ADP and collagen compared to 15 healthy individuals (59.5 % vs. 87.6 %, p < .0001, 43.6 % vs. 79.9 %, p < .0001, 26.1 % vs. 75.2 %, p < .0001, 67.2 % vs. 86 %, p < .0001, respectively). Reduced responses to ADP and collagen were also recorded in patients treated with other agents (n = 16) compared to healthy controls but without difference between the two treatment groups. Aggregation response to ristocetin was normal in all three groups. None of the patients yielded enhanced platelet aggregation. In TPO-RA-treated patients, a strong positive correlation between platelet counts and aggregation response to ristocetin was observed (rs = 0.65, p = .0005). PMP levels were significantly elevated in TPO-RA-treated patients compared to patients treated with other agents (49.5 vs 4.5 events/uL, p < .0001) and healthy controls (5 events/uL, p < .0001). ConclusionsThese results suggest that TPO-RAs may not enhance platelet aggregation responses, whereas impaired responses may be a disease feature. Furthermore, TPO-RAs may increase PMP levels and thus be implicated in the modulation of platelet function in ITP patients.

Immune thrombocytopenia: current diagnostics and therapy : The new 2023 expert report in brief

Immune thrombocytopenia (ITP) is an acquired thrombocytopenia caused by an autoimmune reaction against platelets in the blood and against megakaryocytes in the bone marrow. The indication for treatment is based on the bleeding symptoms and patient-specific factors. This article presents the current 2023 expert report that also forms the basis for the updated version of the Onkopedia guideline, which is expected in the course of 2024. In addition to the background to pathogenesis and pathophysiology, the article discusses clinical manifestations and diagnostics, as well as first-, second- and third-line therapy, including the management of emergency situations. Practice-relevant recommendations are given on the use and side effects of glucocorticoids, as well as on therapy with thrombopoietin receptor agonists (TRA), including the withdrawal regimen, and on treatment with asyk inhibitor.

Insights on treatment of adult ITP: algorithm for management and role of multimodal therapy.

The management of immune thrombocytopenia (ITP) is continuously evolving with the development and introduction of newer therapies and a better understanding of the disease. Corticosteroids still represent the cornerstone of first-line treatment. Patients who fail to achieve remission with a short course of corticosteroids require subsequent therapy. Most guidelines recommend starting with either a thrombopoietin receptor agonist (TPO-RA), rituximab, or fostamatinib since these agents have been investigated in randomized trials and have well-characterized efficacy and safety profiles. Patients' involvement to reach a shared decision regarding choice of therapy is essential as these treatments have different modes of administration and mechanisms of action. Less than 10% will fail to respond to and/or be intolerant of multiple second-line therapeutic options and thus be considered to have refractory ITP and require a third-line therapeutic option. Such patients may require drugs with different targets or a combination of drugs with different mechanisms of action. Combining a TPO-RA and an immunomodulatory agent may be an appropriate approach at this stage. Many studies have been conducted during the last 2 decades investigating the efficacy and safety of combinations strategies for first and later lines of therapies. Yet none of these are recommended by current guidelines or have gained wide acceptance and consensus.

Romiplostim, low-dose rituximab and high-dose dexamethasone for newly diagnosed immune thrombocytopenia: A pilot study.

Therapies such as corticosteroids, thrombopoietin receptor agonists and immunomodulators have been consistently under the spotlight in the search for a better treatment for immune thrombocytopenia (ITP). However, none of them has been widely embraced as a new standard. In this pilot study, we investigated feasibility, safety and preliminary efficacy of romiplostim, low-dose rituximab and high-dose dexamethasone for newly diagnosed ITP. We conducted a single-centre single-arm pilot. One-month treatment adherence was 100%. The 1-month overall response rate was 92.3%. Complete response occurred in 11 (84.6%) patients. Median duration of response was 4.13 monts (range 0.2-25). No serious adverse events presented.

A real-world disproportionality analysis of FDA adverse event reporting system (FAERS) events for avatrombopag

Avatrombopag is a next-generation thrombopoietin receptor agonist approved for the treatment of thrombocytopenia in patients with chronic liver disease scheduled to undergo surgery and thrombocytopenia in patients with chronic immune thrombocytopenia. However, realistic data on its post-marketing long-term safety and tolerability in large sample populations are incomplete. The adverse event (AE) reports of avatrombopag were analyzed based on the FAERS database. By extracting large-scale data from the FAERS database, this study used various signal quantification techniques such as reporting odds ratios, proportional reporting ratios, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker to calculate and evaluate the ratio and association between avatrombopag and specific AEs. In the FAERS database, data from the second quarter of 2018 to the fourth quarter of 2023 were extracted for this study, a total of 1217 avatrombopag-related AEs reports were included for analysis. Based on four calculation methods, this study identified and 32 preferred terms associated with avatrombopag. Common AEs in the product label such as thrombosis, headache, contusion, petechiae, and gingival bleeding were detected. AEs not mentioned in the product label, such as photopsia and ear discomfort were also detected. The first 30 days after initiation of medication were the most common period for both serious and non-serious AEs. This study demonstrates the common AEs and the potential AEs associated with avatrombopag in real-world practice, which could provide valuable cautionary evidence for clinicians and pharmacists to manage safety issues with avatrombopag.

Thrombopoietin mimetic reduces mouse lung inflammation and fibrosis after radiation by attenuating activated endothelial phenotypes.

Radiation-induced lung injury (RILI) initiates radiation pneumonitis and progresses to fibrosis as the main side effect experienced by patients with lung cancer treated with radiotherapy. There is no effective drug for RILI. Sustained vascular activation is a major contributor to the establishment of chronic disease. Here, using a whole thoracic irradiation (WTI) mouse model, we investigated the mechanisms and effectiveness of thrombopoietin mimetic (TPOm) for preventing RILI. We demonstrated that administering TPOm 24 hours before irradiation decreased histologic lung injury score, apoptosis, vascular permeability, expression of proinflammatory cytokines, and neutrophil infiltration in the lungs of mice 2 weeks after WTI. We described the expression of c-MPL, a TPO receptor, in mouse primary pulmonary microvascular endothelial cells, showing that TPOm reduced endothelial cell-neutrophil adhesion by inhibiting ICAM-1 expression. Seven months after WTI, TPOm-treated lung exhibited less collagen deposition and expression of MMP-9, TIMP-1, IL-6, TGF-β, and p21. Moreover, TPOm improved lung vascular structure, lung density, and respiration rate, leading to a prolonged survival time after WTI. Single-cell RNA sequencing analysis of lungs 2 weeks after WTI revealed that TPOm shifted populations of capillary endothelial cells toward a less activated and more homeostatic phenotype. Taken together, TPOm is protective for RILI by inhibiting endothelial cell activation.

Outcomes of Blast-Phase MPN and JAK2, MPL, and CALR Mutated de Novo AML Compared to AML with Wild-Type JAK2, MPL, and CALR Genes: A Propensity Score-Adjusted Cohort Study

Outcomes of Blast-Phase MPN and JAK2, MPL, and CALR Mutated de Novo AML Compared to AML with Wild-Type JAK2, MPL, and CALR Genes: A Propensity Score-Adjusted Cohort Study

LMAN1 serves as a cargo receptor for thrombopoietin.

Thrombopoietin (TPO) is a plasma glycoprotein that binds its receptor on megakaryocytes (MK) and MK progenitors, resulting in enhanced platelet production. The mechanism by which TPO is secreted from hepatocytes remains poorly understood. LMAN1 and MCFD2 form a complex at the endoplasmic reticulum membrane, recruiting cargo proteins into COPII vesicles for secretion. In this study, we showed that LMAN1 deficient mice (with complete germline LMAN1 deficiency) exhibited mild thrombocytopenia, whereas the platelet count was entirely normal in mice with approximately 7% Lman1 expression. Surprisingly, mice deleted for Mcfd2 did not exhibit thrombocytopenia. Analysis of peripheral blood from LMAN1 deficient mice demonstrated normal platelet size and normal morphology of dense and alpha granules. LMAN1 deficient mice exhibited a trend toward reduced MK and MK progenitors in the bone marrow. We next showed that hepatocyte-specific but not hematopoietic Lman1 deletion results in thrombocytopenia, with plasma TPO level reduced in LMAN1 deficient mice, despite normal Tpo mRNA levels in LMAN1 deficient livers. TPO and LMAN1 interacted by co-immunoprecipitation in a heterologous cell line and TPO accumulated intracellularly in LMAN1 deleted cells. Altogether, these studies confirmed the hepatocyte as the cell of origin for TPO production in vivo and were consistent with LMAN1 as the endoplasmic reticulum cargo receptor that mediates the efficient secretion of TPO. To our knowledge, TPO is the first example of an LMAN1-dependent cargo that is independent of MCFD2.

Thrombopoietin Receptor Agonist Added to Standard Immunosuppressive Therapy for Hepatitis-Associated Aplastic Anemia

Background: Hepatitis-associated aplastic anemia (HAAA) is a rare variant of severe aplastic anemia (SAA) characterized with a syndrome of bone marrow failure that traditionally occurs within 6 months of an acute attack of hepatitis. HAAA is potentially lethal if left untreated. Management includes immunosuppression with antithymocyte globulin and cyclosporine and allogeneic hematopoietic stem cell transplantation. Addition of thrombopoietin receptor agonist (TPO-RA) improves both the overall response rate and complete response rate of SAA patients. Here, we tried to investigate the effect and adverse events of TPO-RA added to standard immunosuppressive therapy for HAAA. Methods: A total of 17 HAAA patients who received ATG, cyclosporine and TPO-RA as first-line treatment between April 2019 and January 2024 were enrolled. 6 patients were SAA and 11 patients were very severe aplastic anemia (VSAA) according to the criteria of the International Aplastic Anemia Study Group. All TPO-RAs were added within 1 months after ATG initiation at dose of their standard administration respectively. Results: Of all the patients, 8 received avatrombopag (2 with SAA and 6 with VSAA), 5 received eltrombopag (1 with SAA and 4 with VSAA), and 4 received hatrombopag (3 with SAA and 1 with VSAA). The median neutrophil count was 0.23 (range 0.01-0.78) ×109/L, median reticulocyte count was 11 (range 1-40) ×109/L, and median platelet count was 5 (range 1-12) ×109/L. All patients achieved the end-point of 3 months and 16 patients achieved the end-point of 6 months. The rate of complete response was 11.8% and rate of overall response was 52.9% at 3 months. The rate of complete response at 6 months was 41.2% and rate of overall response was 70.6%. The overall response rate of patients treated with avatrombopag, eltrombopag and hatrombopag were 37.5% vs 40% vs 100%, and 62.5% vs 60% vs 100% at 3, 6 months after IST, respectively. The overall response rate at 3 months and 6 months were both higher than historical results of standard IST (ATG and cyclosporine, 34.1% at 3 months and 56.1% at 6 months). All TPO-RAs were safe, and there was no drug-related liver dysfunction. No patient discontinued TPO-RA due to adverse events. Conclusions: In conclusion, the addition of TPO-RA to IST was safe and associated with higher overall response rate among patients with HAAA.

Comparative Study of Treatment Outcomes of Patients of Aplastic Anemia with Combination Therapy Cyclosporine a + Danazol+ Eltrombopag Versus Cyclosporine a + Danazol + High Dose Romiplostim

Introduction In aplastic anemia (AA), pancytopenia and hypocellular bone marrow occur without aberrant infiltration or reticulin. Acquired AA frequently comes from an autoimmune attack on hematopoietic stem/progenitor cells, while inherited versions include Fanconi anemia, Dyskeratosis Congenita, etc. Symptoms of peripheral blood cytopenia include tiredness, bruising, and bleeding. Blood counts, bone marrow biopsy, and exclusion of Paroxysmal Nocturnal Hemoglobinuria (PNH) and hypoplastic Myelodysplastic Syndrome (hMDS) establish the diagnosis. Immunosuppressive therapy (IST) and hematopoietic stem-cell transplantation (HSCT) are frequent therapies. However, socioeconomic constraints can limit access. Recently, thrombopoietin receptor agonists (TPO-RAs) such as Eltrombopag and Romiplostim have shown potential in AA hematopoiesis. This pilot trial compared the treatment outcomes of Cyclosporine A + Danazol + Eltrombopag vs. high-dose Romiplostim in patients not choosing HSCT and ATG. Methodology The hospital-based open-labeled clinical trial was started after proper registration in the Clinical Trial Registry of India. Patients were allocated into two groups as per their choice. Group A (n=10) received Eltrombopag, Cyclosporine A, and Danazol, while Group B (n=6) received Romiplostim, Cyclosporine A, and Danazol. All consenting adult patients diagnosed with AA were included, and those who had undergone HSCT or had viral infections or significant PNH clones were excluded. The primary outcomes measured were changes in hemoglobin (Hb), total leukocyte count (TLC), and platelet count (PLC) at 3 and 6 months. Results This prospective pilot study included 16 newly diagnosed AA patients divided into two groups. Ten patients recruited in Group A had a median age of 42 years, and that of Group B was 58 years [16 -70 years]. 4/10 were females in Group A (40%), and all were males in Group B. At baseline, Group A had median Hb of 5.7gm/dl [2.5-7.2gm/dl], TLC of 1600/cumm [830-3910/cumm] and PLC of 26,000/cumm [4000-45,000/cumm]. For Group B the median baseline Hb was 4.2gm/dl [3.2-6.1gm/dl], TLC of 1250/cumm [800-2100/cumm] and PLC of 12,000/cumm [10000-16,000/cumm]. At the 3-month follow-up, Group A showed a 0.2 times increase in PLC, while Group B was doubled. At the 6-month follow-up, Group A showed a 1.2 times increase compared to 3 months and a 1.6 times increase compared to baseline. Group B showed a 1.2 times increase compared to 3 months and a 3.6 times increase compared to baseline. Hemoglobin and TLC values followed similar trends, with both groups showing increases at 3 and 6 months but without significant differences between the groups. The median counts at 6 months, of Group A was Hb 9.45gm/dl [6.4-12.1gm/dl], TLC 3065/cumm[ 2170-8000/cumm], and PLC 57,000/cumm [16000-140000/cumm]. While the median counts for Group B was Hb 7.8gm/dl[7.2-8.4gm/dl], TLC 4100/cumm [3600-5280/cumm] and PLC 60,000/cumm [ 46,000-70,000/cumm]. However, the change in both groups was not statistically significant on Mann-Whitney Test and Kruskal-Wallis Test. Kolmogorov was also done since the arms were mismatched. Both groups showed a marked reduction in transfusion dependency from 90% and 100% at induction to 20% and 50% at 6 months. Two patients expired in Group A and one in Group B. Discussion The study found that both combination therapies led to significant increases in Hb, TLC, and PLC over six months, with no significant differences between Group A and Group B. Financial and logistical constraints often precluded patients from receiving HSCT and ATG therapy. Previous studies have shown varying response rates to these therapies, with some reporting higher efficacy for Romiplostim. The current study, however, did not find a significant difference in response between the two groups. Notably, none of the patients experienced significant adverse effects requiring dose modification or treatment interruption. The injectable nature and higher cost made romiplostim a poorer choice among patients. Conclusion This pilot study demonstrated that Eltrombopag and high-dose Romiplostim effectively managed AA patients. Given the socioeconomic barriers, these findings suggest that alternative IST regimens can provide viable and effective treatment options for patients. Further research with larger cohorts and longer follow-ups is needed to validate these results and assess long-term outcomes.

A Better Efficacy of an Escalating Strategy over Thrombopoietin Receptor Agonist-Based Second-Line Therapy in Children Severe Persistent/Chronic Thrombocytopenia: A Multicenter Prospective Study from China

A Better Efficacy of an Escalating Strategy over Thrombopoietin Receptor Agonist-Based Second-Line Therapy in Children Severe Persistent/Chronic Thrombocytopenia: A Multicenter Prospective Study from China

Long-term follow-up of the STOPAGO study

AbstractIn an open prospective, multicenter study enrolling 48 selected patients with chronic immune thrombocytopenia who achieved complete response for 1 year on thrombopoietin receptor agonists, half of the patients maintained a sustained response off treatment 4 years after treatment discontinuation.

Extension of impurity profiling on eltrombopag olamine to in-silico predictions: An effort to exploit correlated forced degradation products and known drug-related substances in drug discovery

The recent pandemic has highlighted the impact of diseases on global health and the economy. The rapid discovery of new hit molecules remains a tough challenge. Pharmaceutical impurity profiling can be linked to drug discovery through the identification of new hits from compounds identified during the analytical profiling. The present study demonstrates this linkage through the extension of the impurity (forced degradation) profiling of eltrombopag (ELT) olamine, a thrombopoietin (TPO) receptor agonist. The drug was exposed to standard degradation and the degradation products were primarily resolved and identified by UPLC-ESI-MS. This led to the identification of five forced degradation products (FDP). Thirty-three other known related substances (RS) of ELT, identified in the literature, were also considered. Molecular similarity checks were performed using Tanimoto/Jaccard's similarity searches. A set of structurally and topologically similar molecules, including ELT and 15 RS, was established and subjected to in-silico toxicity-, absorption-, distribution-, metabolism-, and elimination (ADME) predictions. The RS, predicted with similar or lower toxicity than ELT and a comparable ADME profile, were subjected to molecular docking to trace changes in TPO receptor affinity. The results indicated that five RS had a high Jaccard’s similarity with ELT and higher or comparable docking scores. These compounds, along with few other impurities were predicted to have lower toxicity, better or comparable absorption, distribution, metabolism, and also a better excretion profile than ELT. This justifies their entry as potential novel TPO receptor agonists in drug discovery.

Analysis of Molecular Testing for Suspected Myeloproliferative Neoplasm at a Hybrid Community-Academic Health System

Testing for somatic mutations in JAK2, MPL, and CALR genes is a crucial element in the diagnosis of myeloproliferative neoplasms (MPN). This may have inadvertently led to increased requests for testing to “rule out MPN,” including clinical situations with low pre-test probability. This paper examines JAK2, MPL, and CALR testing by next generation sequencing (NGS) with the goal of formulating practical guidelines to make test utilization more efficient and effective. NGS results from 1482 patients tested between 2015 and March 2022 were retrieved, along with corresponding bone marrow biopsies and CBC results performed within 90 days prior to NGS and 245 (16.5%) cases were positive for pathogenic variants in JAK2, MPL, or CALR genes.The findings showed an increase in the proportion of positive cases with patient age, and a statistically significant difference in RBC counts and platelet counts among patients with positive versus negative results. Utilizing these factors, simple algorithms were constructed to predict positive results with a maximum sensitivity of 91%, while potentially eliminating 28% of negative tests. However, these models still failed to identify ∼9% of patients with MPNs. Among these “missed” patients, many had either primary myelofibrosis or MDS/MPN. Considering a simple triage model to help guide MPN testing could represent a more cost effective approach, particularly if “missed” patients could be further reduced.

Predictors for spontaneous remission in childhood chronic immune thrombocytopenia.

This study examined the factors associated with spontaneous remission in children with chronic immune thrombocytopenia (ITP). We retrospectively analyzed the medical records of patients diagnosed with ITP from January 1988 to December 2019 at our institute. A total of 104 children with chronic ITP were identified. The median follow-up time from diagnosis of chronic ITP was 3.6 years (IQR 1.2-8.3, range 0.1-31.4). Fifteen (14.4%) patients with severe symptoms received specific platelet-elevating therapies, including splenectomy, rituximab, and thrombopoietin receptor agonists. Seven of them achieved remission. Among the patients with a platelet count < 30 × 109/L at the time of diagnosis of chronic ITP, those who received specific platelet-elevating therapies had a higher remission rate compared to those who did not (HR: 4.66, 95% CI: 1.36-16.0). Sixteen patients (15.4%) developed systemic lupus erythematosus, 46 (44.2%) still had thrombocytopenia after a median follow-up of 6.8 years, and 42 (40.4%) achieved remission with a median time to remission of 2.0 years (IQR 0.6-4.1, range 0.1-15.7). The two independent predictive factors for spontaneous remission in childhood chronic ITP were platelet counts > 30 × 109/L at the time of diagnosis of chronic ITP (HR: 3.16, 95% CI: 1.51-6.62) and persistently negative ANA at follow-up (HR: 6.12, 95% CI: 1.46-25.7). The cumulative probabilities of spontaneous remission at 10 years post-diagnosis of chronic ITP were 72.2% for patients without risk factor compared to 0% for patients with two risk factors.

New approaches to standard of care in early-phase myeloproliferative neoplasms: can interferon-α alter the natural history of the disease?

The classical BCR::ABL-negative myeloproliferative neoplasms (MPN) include Polycythemia Vera (PV), Essential Thrombocytemia (ET), and Primary Myelofibrosis (PMF). They are acquired clonal disorders of the hematopoietic stem cells (HSC) leading to hyperplasia of one or several myeloid lineages. MPN are caused by three main recurrent mutations, JAK2V617F and mutations in the calreticulin (CALR) and the thrombopoietin receptor (MPL) genes. Here, we review the general diagnosis, the complications, and the management of MPN. Second, we explain the physiopathology of the natural disease development and its regulation, which contributes to MPN heterogeneity. Thirdly, we describe the new paradigm of the MPN development highlighting the early origin of driver mutations decades before the onset of symptoms and the consequence on early detection of MPN cases in the general population for early diagnosis and better medical management. Finally, we present the interferon alpha (IFNα) therapy as a potential early disease-modifying drug after reporting its good hematological and molecular efficacies in ET, PV and early MF in clinical trials as well as its mechanism of action in pre-clinical studies. As a result, we may expect that, in the future, MPN patients will be diagnosed very early during the course of disease and that new selective therapies under development, such as IFNα, JAK2V617F inhibitors and CALRmut monoclonal antibodies, would be able to intercept the mutated clones.

Desialylation and Apoptosis in Immune Thrombocytopenia: Implications for Pathogenesis and Treatment.

Immune thrombocytopenia (ITP) is an autoimmune disease in which platelet autoantibodies play a significant role in its pathogenesis. Regulatory T cell dysfunction and T cell-mediated cytotoxicity also contribute to thrombocytopenia. Current therapies are directed towards immune suppression and modulation as well as stimulation of platelet production with thrombopoietin receptor agonists. Additional mechanisms of the pathogenesis of ITP have been suggested by recent experimental data. One of these processes, known as desialylation, involves antibody-induced removal of terminal sialic acid residues on platelet surface glycoproteins, leading to hepatic platelet uptake and thrombocytopenia. Apoptosis, or programmed platelet death, may also contribute to the pathogenesis of ITP. The extent of the impact of desialylation and apoptosis on ITP, the relative proportion of patients affected, and the role of antibody specificity are still the subject of investigation. This review will discuss both historical and new evidence of the influence of desialylation and apoptosis in the pathogenesis of ITP, with an emphasis on the clinical implications of these developments. Further understanding of both platelet desialylation and apoptosis might change current clinical practice and improve patient outcomes.

Avatrombopag for the treatment of patients with chemotherapy-induced thrombocytopenia: A case series.

Management of chemotherapy-induced thrombocytopenia (CIT) is challenging, often resulting in chemotherapy treatment delays, dose reduction, and treatment interruption. Randomized trials support the potential efficacy and safety of thrombopoietin receptor agonists in CIT management. A phase III trial of avatrombopag (AVA) demonstrated increased platelet counts (PC) in patients with solid tumours experiencing CIT. To complement those findings, this case series of six patients with solid tumours and CIT is presented. Results from these cases support the clinical benefit of AVA in improving PC and reducing the impact of CIT on tumour treatment, allowing continued therapy without dose reduction or treatment interruption.

Clinical research progress of lusutrombopag for the treatment of thrombocytopenia in chronic liver disease

Thrombocytopenia is one of the common complications with the hematologic system in patients with chronic liver disease, which often causes poor quality of life and high risk of bleeding, thereby affecting their diagnosis, treatment, and prognosis. Platelet transfusion can improve the patient's declining platelet count to a certain extent, but it has problems such as high price and being easy to cause immune rejection. Thrombopoietin (TPO), as an important cytokine that affects platelet production, can bind to TPO receptors and activate megakaryocytes to produce platelets. Lusutrombopag is a newly developed small-molecule TPO receptor agonist that can induce bone marrow progenitor cells to differentiate into megakaryocytes and increase platelet production, posing characteristics of oral convenience, safety and effectiveness; thus, it has been used in many countries and regions for the treatment of patients with chronic liver diseases concurrent with thrombocytopenia. Herein, the pharmacological features and clinical research are reviewed.