{"paper_id":"0f26f67e-4e14-4033-80e6-524900b683d2","body_text":"Multicenter, Real-World Observational Study of AVA Therapy Following ELT/HET Switching in Chinese Children with Persistent/Chronic Primary ITP | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Multicenter, Real-World Observational Study of AVA Therapy Following ELT/HET Switching in Chinese Children with Persistent/Chronic Primary ITP Jingjing Liu, Zhifa Wang, Nan Wang, Jingyao Ma, Lijuan Wang, Yan Liu, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6187960/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 11 Sep, 2025 Read the published version in Annals of Hematology → Version 1 posted 10 You are reading this latest preprint version Abstract Avatrombopag (AVA), a second-generation thrombopoietin receptor agonist (TPO-RA), has demonstrated efficacy in pediatric persistent/chronic immune thrombocytopenia (ITP). However, critical evidence gaps persist regarding treatment-switching strategies between TPO-RAs, particularly when transitioning from eltrombopag (ELT) or hetrombopag (HET) to AVA. This multicenter cohort study evaluated 55 pediatric ITP patients unresponsive to or relapsing after ELT (n = 46) or HET (n = 9) who underwent AVA switch therapy. Outcomes included platelet response (≥ 30×10⁹/L without rescue therapy), bleeding events, concomitant medication reduction, and safety. Sustained response rates reached 48.4% (ELT-to-AVA) and 33.3% (HET-to-AVA), with median response durations of 10 and 7 days respectively. Platelet elevation during AVA treatment was resolved with dosage changes or discontinuation. AVA significantly reduced bleeding, ITP medications, and rescue therapy, with side effects such as gastrointestinal symptoms, headaches, and fatigue (grades 1–2). AVA demonstrates potential as a safe and effective bridging therapy for TPO-RA refractory pediatric ITP, offering hematological stabilization while reducing treatment burden. These findings address current evidence deficiencies in TPO-RA switching protocols. immune thrombocytopenia thrombopoietin receptor agonists eltrombopag hetrombopag avatrombopag Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Immune thrombocytopenia (ITP) is the most common bleeding disorder in children and is primarily characterized by thrombocytopenia. Abnormal immune responses, result in inadequate platelet production, or increased platelet destruction typically causes it. Although the exact etiology remains unclear, current studies suggest that multiple factors contribute to its pathogenesis, including aberrant T-cell- and B-cell-mediated immune responses, cytokine imbalances, and megakaryocyte damage, ultimately resulting in impaired platelet production and increased destruction[ 1 , 2 ]. Although the majority of pediatric patients with ITP are self-limiting, approximately a quarter or one-third of patients progress to chronic ITP [ 3 ], where maintaining long-term platelet counts becomes challenging with standard therapies. International reports estimate the annual incidence of pediatric ITP to be 2–5 per 100,000 children[ 4 ]. The initial treatment of pediatric ITP typically involves corticosteroids or intravenous immunoglobulin (IVIG). However, approximately one-third of the patients either relapse or fail to respond to first-line therapies. With evolving treatment paradigms, the focus of ITP management has shifted from merely increasing platelet counts to reducing bleeding episodes and improving patients’ quality of life[ 5 ]. Thrombopoietin receptor agonists (TPO-RAs) have emerged as critical second-line therapy. The 2019 ASH guidelines recommend TPO-RAs followed by rituximab (RTX) and splenectomy as second-line treatments for ITP [ 4 ]. TPO-RAs, including eltrombopag (ELT), hetrombopag (HET), romiplostim, and avatrombopag (AVA), stimulate platelet production by mimicking the action of thrombopoietin (TPO) on its receptor and promoting megakaryocyte proliferation and differentiation in the bone marrow. The main advantage of TPO-RAs is their specificity for enhancing platelet production without immunosuppressive effects or severe infection risks associated with RTX or splenectomy, making them suitable for long-term use. Studies have demonstrated that TPO-RAs significantly increase platelet counts and reduce bleeding risk in pediatric patients with ITP[ 6 – 8 ]. Despite the proven efficacy of TPO-RAs, a subset of patients either do not respond to ELT or HET or experience a loss of effectiveness over time. This highlights the need to explore the differential effects of various TPO-RAs in pediatric ITP treatment. Our previous study showed that switching to AVA could be effective and safe in patients with chronic ITP who fail to respond to ELT[ 9 ]. AVA, a newer generation TPO-RA, offers advantages, such as no requirement for fasting, better tolerability, and less susceptibility to hepatic function variations, making it a promising alternative for these patients [ 4 , 6 ] This study aimed to evaluate the efficacy and safety of switching from ELT or HET to AVA in treating pediatric ITP, providing clinical evidence and theoretical support for switching therapy in cases in which ELT or HET are ineffective or have lost efficacy. Method This multicenter, retrospective, observational cohort study was conducted in July 2024 and enrolled children with ITP treated with AVA at three referral children's hospitals in July 2024 to collect data from Aug 2021 to May 2024 (This study includes seven patients from the prior study[ 9 ]). For this retrospective study, ethics approval was obtained from the institutional review boards of Beijing Children′s Hospital, Capital Medical University (Ethics approval NO. [2024]-Y-098-D). Informed consent was obtained from the patients and their guardians via telephone prior to the commencement of the study. Inclusion and exclusion criteria Inclusion criteria were as follows: 1) Aged 0 to 18 years diagnosed with ITP for more than three months; 2) lack of sustained response to first-line treatments (glucocorticoids, IVIG) with platelet counts below 30×10 9 /L and no response after treatment with ELT or HET; and 3) medication duration of at least two months and a total observation period exceeding two months. The exclusion criteria were as follows: 1) Diagnosis of secondary thrombocytopenia; 2) The legal guardian refused to participate in the study. Definitions and outcomes [ 4 ] Response: a) Complete response (CR): Complete platelet response was defined as a platelet count of ≥ 100×10 9 /L with no bleeding within two months. b) Response (R): Platelet response was defined as a platelet count of 30–100×10 9 /L, with at least a two-fold increase in platelet count from baseline and no bleeding within two months. c) No response (NR): platelet count < 30×10 9 /L, less than a two-fold increase from the baseline count, or bleeding after dose titration of AVA within two months. d) Overall response (OR): total number of patients who achieved CR and R. Sustained response (SR): platelet count > 30×10 9 /L following an AVA dose at ≥ 75% of the platelet count assessment at week 24 since the patient achieved a response. Rescue therapy: Based on the clinical assessment, platelet transfusion or IVIG therapy was administered at the investigator’s discretion. Rescue therapy was initiated when the platelet count dropped below 20×10 9 /L, and bleeding severity was graded as 3–4. Bleeding grades.[ 10 ]: The Working Group of the Chinese Guidelines for the Diagnosis and Treatment of Childhood Primary Immune Criteria categorized bleeding into four grades (grade 0, no bleeding; grade 1, petechiae; grade 2, mild blood loss; grade 3, gross blood loss; and grade 4, debilitating blood loss) Adverse events (AEs): These were evaluated using the National Cancer Institute Common Toxicity Criteria, version 5.0 (CTCAE version 5.0). [ 11 ]. Thrombocytosis was defined as a platelet count of ≥ 400×10 9 /L on one or more measurements using AVA. Follow-up protocol: Based on the severity of bleeding, Platelet count was required to be monitored weekly for the first month after AVA treatment and at least monthly thereafter. Statistical analysis Normally and non-normally distributed continuous variables are shown as medians and quarters (Q1 and Q3), and non-normally distributed variables were analyzed using non-parametric t-tests (Mann–Whitney U test). Single-factor analysis was performed using the chi-square test or Fisher's exact probability test, with statistical significance set at a significance level of p < 0.05. All analyses were performed using the GraphPad Prism 9.0. Results A total of 67 patients with thrombocytopenia switched from ELT or HET to AVA. Among them, 6 patients were diagnosed with secondary ITP, four received AVA for less than 8 weeks, and two had newly diagnosed ITP. Ultimately, 55 patients were included in the study, comprising 46 who switched from ELT to AVA and 9 who switched from HET to AVA. (Figure 1) General characteristics of enrolled patients Based on previous medications, patients were divided into the ELT-switch and HET-switch groups. The median diagnostic age of patients in the two groups was 4.3 years (2.2 years, 7.8 years) and three years (0.8 years, 6.3 years), respectively. Of the 55 patients, 30 were male, with 25 in the ELT-switch group and 5 in the HET-switch group. The median time from ITP diagnosis to the initiation of AVA was 1.9 years (1.0 years, 2.5 years) in the ELT-switch group and 0.9 years (0.2 years, 4.9 years) in the HET-switch group. In the ELT-switch group, 42 patients had received High-Dose dexamethasone (HDD) treatment, and 33 had undergone RTX therapy, compared to seven patients who had received HDD and four patients who had undergone RTX in the HET-switch group. The median duration of ELT treatment before switching to AVA was 4.8 months (2.3 months,12.9 months), and for HET, it was 2 months (2 months, 3.5 months). The median platelet count at the time of ITP diagnosis was 11×10 9 /L (5×10 9 /L, 19×10 9 /L) in the ELT switch group and 12×10 9 /L (4×10 9 /L, 16×10 9 /L) in the HET switch group, with no significant difference ( p = 0.699). The median duration of AVA treatment post-switch was 12.9 months (6 months, 6.9 months) in the ELT-switch group and 8.6 months (4.6 months, 16.8 months) in the HET-switch group. All characteristics of patients in the ELT-switch and HET-switch groups showed no statistically significant differences (all p > .05) (Table 1). Table 1 Patient characteristics Variable Switch from ELT (n=46), % Switch from HET (n=9), % p value Age, median (IQR), year 4.3(2.2-7.8) 3(0.8-6.3) 0.711 Gender, male (n) 25 5 >0.99 Type of ITP (n) persistent ITP 12 4 0.422 chronic ITP 34 5 Time since diagnosis, median (IQR), year 1.9(1.0-2.5) 0.9(0.2-4.9) 0.233 The prior treatment before initiation of AVA Prior HDD, n (%) 42(91.3%) 7(77.8%) 0.750 Prior RTX, n (%) 33(71.7%) 4(44.4%) Time of TPO-RAs before initiation of AVA, median (IQR), month 4.8(2.3-12.9) 2(2-3.5) 0.079 Dose of TPO-RAs before initiation of AVA, median (IQR), (mg/kg/d) 1.3(1.1-1.7) 0.13(0.11-0.14) - Platelet count diagnosed, median (IQR), (×10 9 /L) 11(5-19) 12(4-16) 0.699 Follow-up with AVA treatment, median (IQR), month 12.9(6-16.9) 8.6(4.6-16.8) 0.445 Abbreviation: ITP, Immune thrombocytopenia; ELT, eltrombopag; HET, hetrombopag; AVA, avatrombopag; HDD, high dose dexamethasone; RTX, rituximab. Efficacy In the ELT-switch group, 37 patients achieved an OR, including 28 who achieved a CR, while nine were classified as non-responders (NR). In the HET-switch group, six patients achieved OR, including four who achieved CR, and three were NR. No significant difference was observed between the two groups ( p = 0.597). At six months, the sustained response (SR) rates were 48.4% (18/37) in the ELT-switch group and 33.3% (2/6) in the HET-switch groups, with no significant difference ( p = 0.668). The median effective AVA dosage was 0.73 mg/kg (0.63 mg/kg, 0.86 mg/kg) in the ELT-switch group and 0.9 mg/kg (0.6 mg/kg, 1.0 mg/kg) in the HET-switch group, with no significant difference ( p = 0.174). In the ELT-switch group, 47.8% of the patients had a reduced AVA dosage compared with 33.3% in the HET-switch group, with no statistically significant difference ( p = 0.487) (Table 2). Baseline platelet counts were 18×10 9 /L (8×10 9 /L, 26×10 9 /L) in the ELT-switch group and 19 × 10 9 /L (10×10 9 /L, 28×10 9 /L) in the HET-switch group. After switching to AVA, the platelet count increased to 101×10 9 /L (46×10 9 /L, 175×10 9 /L) and 65×10 9 /L (31×10 9 /L, 99×10 9 /L) at 2 weeks, and to 110×10 9 /L (38×10 9 /L, 189×10 9 /L) and 101×10 9 /L (17×10 9 /L, 172×10 9 /L) at 2 months. At six months, the counts were 103×10 9 /L (40×10 9 /L, 210×10 9 /L) and 66×10 9 /L (40×10 9 /L, 97×10 9 /L), with no statistically significant differences between the groups at any time point ( p >.05) (Figure 2). Table 2 Efficacy of AVA treatment switch from ELT or HET on ITP Switch from ELT Switch from HET p value Response at eight weeks CR, n (%) 28(60.8%) 4(44.4%) R, n (%) 9(19.6%) 2(22.3%) 0.597 NR, n (%) 9(19.6%) 3(33.3%) SR 18/37(48.4%) 2/6(33.3%) 0.668 TTR 10(5,17) 7(5,14) 0.402 Effective AVA dose, mg/kg/d 0.73(0.63,0.86) 0.90(0.60,1.0) 0.174 Taper of AVA 22/46 3/9 0.487 Abbreviation: CR, complete response; R, response; NR, no response; SR, sustained response; TTR, time to response; ELT, eltrombopag; HET, hetrombopag; AVA, avatrombopag. Bleeding improvement At baseline, 69% of the patients (32/46) in the ELT-switch group and 77% of the patients (7/9) in the HET-switch group had bleeding symptoms, including 18 with grade 1, 8 with grade 2, 7 with grade 3, and 1 with grade 4 bleeding in the ELT-switch group, and 4 with grade 1 and 3 with grade 2 bleeding. After one month, three patients had grade 1 bleeding, and two had grade 2 bleeding. After one month of treatment, the number of patients with bleeding decreased to 26% (12/46) and 55% (5/9). After nine or eight months, all bleeding symptoms resolved in both groups (Figure 3). Concomitant medication and rescue therapy At baseline, 36.9% of patients (17/46) in the ELT-switch group and 21.7% of patients (10/46) in the HET-switch group were on concomitant medication, which decreased to 6.5% (3/46) and 11.1% (1/9), respectively. After following for 12 months, the concomitant medication in the ELT-switch group and HET-switch group was decreased to 12.5% and 0, respectively. (Figure 4A). At baseline, 21.7% of patients (10/46) in the ELT-switch group and 22.2% (2/9) in the HET-switch group required rescue therapy. After one month, the rescue therapy rate decreased to 6.5% (3/46) and 11.1% (1/9), respectively. After following for 12 months, the rescue therapy in the ELT-switch group and HET-switch group was decreased to 6% and 0, respectively. (Figure 4B). TRAEs The most common treatment-related adverse event was an elevated platelet count, which occurred in 19/46 (41.3%) patients in the ELT-switch group and 3/9 (33.3%) patients in the HET-switch group; no thrombotic complications occurred during the treatment. In the ELT group, five patients (10.8%) experienced gastrointestinal symptoms such as vomiting and diarrhea, and two patients (4.3%) reported headaches, with one patient (2.1%) feeling fatigued after taking the medication. One patient (11.1%) in the HET group developed gastrointestinal symptoms. (Table 3). Table 3 Treatment-related adverse events Switch from ELT,(n=46), % Switch from HET,(n=9), % Platelet elevation 19(41.3%) 3(33.3%) Gastrointestinal reactions 59(10.9%) 1(11.1%) Headache 2(4.3%) 0 Fatigue 1(2.2%) 0 Discussion TPO-RAs, including small molecules such as ELT, HET, and AVA, have been widely used as second-line treatments for pediatric ITP because of their sustained efficacy and favorable safety profiles. These drugs activate the Janus kinase-signal transducers and activators of transcription (JAK-STAT) and mitogen-activated protein kinase (MAPK) signaling pathways by binding to the thrombopoietin receptor, stimulating megakaryocyte proliferation, and increasing platelet count [13]. Hetrombopag, the first small-molecule, non-peptide oral TPO-RA developed in China, has demonstrated significant efficacy in a randomized, multicenter, placebo-controlled Phase III trial. The study revealed that compared to placebo, HET significantly increased platelet counts and reduced the risk of bleeding[14]. Clinical studies have shown that TPO-RAs, including small molecules such as ELT and HET and giant peptide drugs such as romiplostim, are both safe and effective in treating pediatric ITP [13]. Though ELT and HET have demonstrated efficacy in both persistent ITP and chronic ITP, patients may develop \"off response\" over time, necessitating a switch to other treatments. The PETIT study demonstrated that 81% of children achieved platelet counts of ≥ 50 × 10⁹/L within 24 weeks of ELT treatment[15] and PETIT 2 reported an 80% OR rate after 24 weeks.[16] However, long-term studies by Wang et al. reported that 18.6% of patients required a switch to another therapy because of a loss of response. [17]. A few patients regained their response to ELT after a break. In contrast, for treatment failures, it is necessary to initiate treatment with other TPO-RAs, such as romiplostim, or alternative therapies, such as daratumumab or RTX, to achieve better management of the condition.[18]. Our previous study observed that patients with failed ELT responded well to AVA, with an OR rate of 81.8% and a CR rate of 54.6%.[9]. AVA, a second-generation TPO-RA, offers advantages over first-generation drugs, such as ELT and HET. AVA does not need to be administered on an empty stomach, carries no risk of iron deficiency anemia with AVA and no known hepatotoxicity signal, and has potent platelet-elevating effects that make it suitable for perioperative thrombocytopenia management. [6]. Pharmacokinetically, AVA reaches its peak plasma concentration 6–8 h post-administration and has a half-life of approximately 19 h, and its efficacy in treating thrombocytopenia in chronic liver disease and in perioperative settings has been validated in ADAPT-1 and ADAPT-2 studies, with 90% of patients avoiding platelet transfusions or rescue therapies during the perioperative period.[19]. Additionally, a multicenter study showed that 79.4% of children achieved OR within four weeks of AVA treatment.[20]. In adult ITP patients who switched to AVA due to the ineffectiveness of ELT or romiplostim, a median follow-up duration of 9.2 months was achieved, demonstrating favorable efficacy and tolerability, with 93% achieving an OR, and 86% achieving CR. [21]. Unlike the previous study, in which patients switched to AVA for various reasons, including adverse events and convenience, all patients in our study switched because of treatment failure or loss of response. In our study, the OR for the ELT and HET switch groups after transitioning to AVA were 82.6% and 80%, respectively, with CR rates of 65.2% and 60%. No significant differences were observed between the groups ( p > 0.05), suggesting that AVA maintains its efficacy in treating ITP when transitioning from ELT or HET. These findings are consistent with those of our earlier study, which showed an OR rate of 81.8% and a CR rate of 54.6% in patients who switched from ELT to AVA. [9]. Furthermore, significant improvements in bleeding were observed after switching to AVA, with the proportion of patients experiencing bleeding decreasing from approximately 70% at baseline to nearly 0% at 8–9 months post-treatment. Concurrent medication use and rescue therapies decreased in patients who responded to AVA, which is consistent with the results of previous studies. [20]. In both groups, platelet counts peaked 1–2 weeks after the start of AVA. In the larger ELT-switch group, platelet counts reached their peak two weeks post-treatment before stabilizing, consistent with Al-Samkari's[21] findings, which attributed the peak to a \"first dose effect\" of AVA, which promotes anti-apoptotic activity in megakaryocytes. [22]. The most common AE observed with AVA was thrombocytosis, which occurred in 41.3% of the patients in the ELT-switch group and 30% in the HET-switch group. Unlike adults, where AVA-associated thrombocytosis is linked to thromboembolic events or bone marrow fibrosis,[6, 23, 24], pediatric patients mainly experience thrombocytosis without thrombotic complications, likely due to the lower prevalence of comorbid conditions such as hyperlipidemia and hyperglycemia. Other common AEs included gastrointestinal symptoms (abdominal pain, diarrhea, and vomiting), which occurred in 10.8% and 10% of the patients in the ELT and HET switch groups, respectively. Additionally, 4.2% and 2.1% of patients in the ELT group experienced headaches and fatigue, respectively. These AEs were not observed in the HET group, potentially because of the small sample size. Previous studies have identified headache as a common AE, occurring in 2 out of 12 patients who discontinued AVA owing to severe AEs.[25] . In our study, two patients reported mild headaches, but no severe AEs were observed. None of the severe AEs commonly reported in adult studies, such as thromboembolism, occurred in the pediatric cohort.[23, 24]. To our knowledge, this is the first large-scale, multicenter study to examine the efficacy and safety of switching to TPO-RAs in Chinese children with ITP. However, this study had several limitations. First, this was a retrospective analysis, and future prospective studies are required. Second, the HET-switch group had a smaller sample size, likely because of the relatively recent introduction of the HET. Future studies should aim to include larger sample sizes and conduct long-term, multicenter, prospective cohort studies. AVA has shown great potential as a second-line treatment for pediatric ITP, with promising results for both persistent ITP and chronic ITP. Reports of its effectiveness exist in adult NITP, further supporting the potential of AVA for broader applications. Although AVA has demonstrated good efficacy and safety, its high cost presents a financial burden compared to ELT and HET, which may limit its use. Families who can afford AVA may be the preferred second-line treatment for pediatric ITP. Declarations ACKNOWLEDGEMENTS The authors thank the patients, their families, and all investigators involved in this study, including physicians and laboratory technicians. CONFLICT OF INTEREST STATEMENT The authors declare that they have no potential conflicts of interest. DATA AVAILABILITY STATEMENT Due to the nature of this research, the participants did not agree for their data to be shared publicly; therefore, supporting data are not available. Further inquiries can be directed to the corresponding authors. FUNDING INFORMATION This work was supported by funding from the Reform and Development of the Beijing Municipal Health Commission, Capital's Funds for Health Improvement and Research (No. 2022-2Z-2099), the Beijing Municipal Administration of Hospitals Incubating Program (No. PX2023044) and National Natural Science Foundation of China (No.81970111). This work was supported in part by grants from the Beijing Municipal Administration of Hospitals Incubating Program (No. PX2022051). AUTHOR CONTRIBUTIONS Runhui Wu and Xiaoling Cheng designed the research. All authors performed the research and collected data. Jingjing Liu interpreted the data and wrote the manuscript. Zhifa Wang, Nan Wang, and Jingyao Ma analyzed the data. Lijuan Wang and Yan Liu participated in data collection. Jinxi Meng and Shuyue Dong completed Figure 1 and Figure 2. Yu Hu and Juntao Ouyang completed Figure 3. Zhenping Chen participated in data analysis. 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Nagalla, Efficacy and safety evaluation of avatrombopag in immune thrombocytopenia: analyses of a phase III study and long-term extension. Platelets, 2022. 33(2): p. 257-264. Tarantino, M.D., et al., A phase 3, randomized, double-blind, active-controlled trial evaluating efficacy and safety of avatrombopag versus eltrombopag in ITP. Br J Haematol, 2023. 202(4): p. 897-899. Bussel, J.B., et al., A randomized trial of avatrombopag, an investigational thrombopoietin-receptor agonist, in persistent and chronic immune thrombocytopenia. Blood, 2014. 123(25): p. 3887-94. Biovitrum., S.O., DOPTELET®(avatrombopag): US prescribing information. 2020: p. Accessed 17 Sep 2021. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 11 Sep, 2025 Read the published version in Annals of Hematology → Version 1 posted Editorial decision: Revision requested 10 Jul, 2025 Reviews received at journal 09 Jul, 2025 Reviewers agreed at journal 29 Jun, 2025 Reviewers agreed at journal 06 Apr, 2025 Reviews received at journal 31 Mar, 2025 Reviewers agreed at journal 28 Mar, 2025 Reviewers invited by journal 18 Mar, 2025 Editor assigned by journal 13 Mar, 2025 Submission checks completed at journal 13 Mar, 2025 First submitted to journal 09 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-6187960\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":431661740,\"identity\":\"285514e4-71f4-4c9e-9ba9-d548fdac7903\",\"order_by\":0,\"name\":\"Jingjing Liu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Capital Medical University, National Center for Children′s Health\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Jingjing\",\"middleName\":\"\",\"lastName\":\"Liu\",\"suffix\":\"\"},{\"id\":431661741,\"identity\":\"2bf160c9-d136-4701-bdcd-14e616962a68\",\"order_by\":1,\"name\":\"Zhifa Wang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Capital Medical University, National Center for Children′s Health\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Zhifa\",\"middleName\":\"\",\"lastName\":\"Wang\",\"suffix\":\"\"},{\"id\":431661742,\"identity\":\"8ac8da15-1f73-43c9-88a5-a42d74b270ff\",\"order_by\":2,\"name\":\"Nan Wang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Department of Pharmacy, Beijing Children's Hospital, Capital Medical University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Nan\",\"middleName\":\"\",\"lastName\":\"Wang\",\"suffix\":\"\"},{\"id\":431661743,\"identity\":\"7adff6d3-ea97-4977-82f8-a2d7ef975e82\",\"order_by\":3,\"name\":\"Jingyao Ma\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Capital Medical University, National Center for Children′s Health\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Jingyao\",\"middleName\":\"\",\"lastName\":\"Ma\",\"suffix\":\"\"},{\"id\":431661746,\"identity\":\"bea15c2d-0804-4d95-8005-ab547bb64037\",\"order_by\":4,\"name\":\"Lijuan Wang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Henan Province Children′s Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Lijuan\",\"middleName\":\"\",\"lastName\":\"Wang\",\"suffix\":\"\"},{\"id\":431661747,\"identity\":\"acd23afd-e884-477c-b42e-3d222214ff28\",\"order_by\":5,\"name\":\"Yan Liu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Baoding Children′s Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yan\",\"middleName\":\"\",\"lastName\":\"Liu\",\"suffix\":\"\"},{\"id\":431661749,\"identity\":\"9ad73ddf-11ff-4867-b9d9-5ba41011cbb2\",\"order_by\":6,\"name\":\"Jinxi Meng\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Capital Medical University, National Center for Children′s Health\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Jinxi\",\"middleName\":\"\",\"lastName\":\"Meng\",\"suffix\":\"\"},{\"id\":431661754,\"identity\":\"c743a7a5-c360-47de-ae38-988a1758334d\",\"order_by\":7,\"name\":\"Shuyue Dong\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Capital Medical University, National Center for Children′s Health\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Shuyue\",\"middleName\":\"\",\"lastName\":\"Dong\",\"suffix\":\"\"},{\"id\":431661759,\"identity\":\"9534b6b4-3bd6-4b91-b4dc-32b81c4c9164\",\"order_by\":8,\"name\":\"Yu Hu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Capital Medical University, National Center for Children′s Health\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yu\",\"middleName\":\"\",\"lastName\":\"Hu\",\"suffix\":\"\"},{\"id\":431661761,\"identity\":\"4a880163-c3f5-4976-a673-e66b496dd1fd\",\"order_by\":9,\"name\":\"Juntao Ouyang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Pediatric Research Institute, Capital Medical University, National Center for Children′s Health\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Juntao\",\"middleName\":\"\",\"lastName\":\"Ouyang\",\"suffix\":\"\"},{\"id\":431661762,\"identity\":\"d3148c7c-90e8-461a-8b3c-3b2ee17ee3ea\",\"order_by\":10,\"name\":\"Zhenping Chen\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Pediatric Research Institute, Capital Medical University, National Center for Children′s Health\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Zhenping\",\"middleName\":\"\",\"lastName\":\"Chen\",\"suffix\":\"\"},{\"id\":431661764,\"identity\":\"496e94cf-adc6-4d59-9b56-a01a4956adcf\",\"order_by\":11,\"name\":\"Xiaoling Cheng\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Department of Pharmacy, Beijing Children's Hospital, Capital Medical University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Xiaoling\",\"middleName\":\"\",\"lastName\":\"Cheng\",\"suffix\":\"\"},{\"id\":431661765,\"identity\":\"c7c03c08-59ec-40a8-b809-3b9b70be4031\",\"order_by\":12,\"name\":\"Runhui Wu\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyUlEQVRIiWNgGAWjYHACNgYGAwYGfgkwR0KGeC2SMxgYG4BaeIjUAgQGN8BaGAhrMZ+Re+wxT8HhxM23m48/ulFjwcPAfvjoBnxaZG7kpRvzGBxO3HbnWGJzzjGgw3jS0m7g0yIhkWMmzWNwO3HbjRzD5hw2oBYJHjPitGyeAdLyjxQtGySAWnLbiNHC88ZMco7Bf+MZN9ISZ+f2SfCwEfQLe46ZxJs/abL9M5IPfM75VifHz374GF4tmICNNOWjYBSMglEwCrABAGDfQm6qqLCrAAAAAElFTkSuQmCC\",\"orcid\":\"\",\"institution\":\"Capital Medical University, National Center for Children′s Health\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Runhui\",\"middleName\":\"\",\"lastName\":\"Wu\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2025-03-09 09:53:26\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-6187960/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-6187960/v1\",\"draftVersion\":[],\"editorialEvents\":[{\"content\":\"https://doi.org/10.1007/s00277-025-06567-9\",\"type\":\"published\",\"date\":\"2025-09-11T15:56:57+00:00\"}],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":79336666,\"identity\":\"c76d3367-3ca4-451c-8ac4-9fdd8f4747da\",\"added_by\":\"auto\",\"created_at\":\"2025-03-27 07:59:48\",\"extension\":\"jpg\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":37755,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eStudy Participant Inclusion Flowchart\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNote: Secondary ITP[12]: Immune thrombocytopenia caused by other underlying conditions. The triggering factors include antiphospholipid syndrome, autoimmune thrombocytopenia (e.g., Evans syndrome), common variable immune deficiency, drug-induced side effects, infections such as cytomegalovirus, Helicobacter pylori, hepatitis C, human immunodeficiency virus, varicella zoster, lymphoproliferative disorders, side effects of bone marrow transplantation, vaccination side effects, and systemic lupus erythematosus.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"1.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6187960/v1/2620ea7eb8a0bab65938c0ca.jpg\"},{\"id\":79337239,\"identity\":\"d68dc5b5-d9f9-48ce-8204-dbd9b98fa568\",\"added_by\":\"auto\",\"created_at\":\"2025-03-27 08:07:47\",\"extension\":\"jpg\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":40775,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eAbbreviation:\\u003c/strong\\u003e ELT, eltrombopag; HET, hetrombopag\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMedian platelet counts(×10\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e9\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003e/L) of patients treated with AVA\\u003c/strong\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"2.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6187960/v1/93c4106e6761524706a309b0.jpg\"},{\"id\":79336634,\"identity\":\"187c1ad4-8fcc-4f7e-85e8-b7e329cc3d55\",\"added_by\":\"auto\",\"created_at\":\"2025-03-27 07:59:47\",\"extension\":\"jpg\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":36727,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003ePatients bleeding reduced after avatrombopag initiation\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e* means switch from eltrombopag; #means switch from hetrombopag\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"3.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6187960/v1/35c6b8dc065651f8581b9817.jpg\"},{\"id\":79336657,\"identity\":\"c5bd9d2a-5d6e-4aac-a688-6ae0c1d007f3\",\"added_by\":\"auto\",\"created_at\":\"2025-03-27 07:59:48\",\"extension\":\"jpg\",\"order_by\":4,\"title\":\"Figure 4\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":79345,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eA Patients requiring concomitant therapy after avatrombopag initiation\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eB Patients requiring rescue therapy after avatrombopag initiation\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAbbreviation:\\u003c/strong\\u003e ELT, eltrombopag; HET, hetrombopag\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"4.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6187960/v1/8944835d727371f8c0470443.jpg\"},{\"id\":91359055,\"identity\":\"fc4cf72f-c18e-4e1a-a5c0-6da0f8f2d307\",\"added_by\":\"auto\",\"created_at\":\"2025-09-15 16:04:38\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":939490,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6187960/v1/eea4917c-281c-4260-a495-42f5d8282261.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Multicenter, Real-World Observational Study of AVA Therapy Following ELT/HET Switching in Chinese Children with Persistent/Chronic Primary ITP \",\"fulltext\":[{\"header\":\"Introduction\",\"content\":\"\\u003cp\\u003eImmune thrombocytopenia (ITP) is the most common bleeding disorder in children and is primarily characterized by thrombocytopenia. Abnormal immune responses, result in inadequate platelet production, or increased platelet destruction typically causes it. Although the exact etiology remains unclear, current studies suggest that multiple factors contribute to its pathogenesis, including aberrant T-cell- and B-cell-mediated immune responses, cytokine imbalances, and megakaryocyte damage, ultimately resulting in impaired platelet production and increased destruction[\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e]. Although the majority of pediatric patients with ITP are self-limiting, approximately a quarter or one-third of patients progress to chronic ITP [\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e], where maintaining long-term platelet counts becomes challenging with standard therapies. International reports estimate the annual incidence of pediatric ITP to be 2\\u0026ndash;5 per 100,000 children[\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eThe initial treatment of pediatric ITP typically involves corticosteroids or intravenous immunoglobulin (IVIG). However, approximately one-third of the patients either relapse or fail to respond to first-line therapies. With evolving treatment paradigms, the focus of ITP management has shifted from merely increasing platelet counts to reducing bleeding episodes and improving patients\\u0026rsquo; quality of life[\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e]. Thrombopoietin receptor agonists (TPO-RAs) have emerged as critical second-line therapy. The 2019 ASH guidelines recommend TPO-RAs followed by rituximab (RTX) and splenectomy as second-line treatments for ITP [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eTPO-RAs, including eltrombopag (ELT), hetrombopag (HET), romiplostim, and avatrombopag (AVA), stimulate platelet production by mimicking the action of thrombopoietin (TPO) on its receptor and promoting megakaryocyte proliferation and differentiation in the bone marrow. The main advantage of TPO-RAs is their specificity for enhancing platelet production without immunosuppressive effects or severe infection risks associated with RTX or splenectomy, making them suitable for long-term use. Studies have demonstrated that TPO-RAs significantly increase platelet counts and reduce bleeding risk in pediatric patients with ITP[\\u003cspan additionalcitationids=\\\"CR7\\\" citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eDespite the proven efficacy of TPO-RAs, a subset of patients either do not respond to ELT or HET or experience a loss of effectiveness over time. This highlights the need to explore the differential effects of various TPO-RAs in pediatric ITP treatment. Our previous study showed that switching to AVA could be effective and safe in patients with chronic ITP who fail to respond to ELT[\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e]. AVA, a newer generation TPO-RA, offers advantages, such as no requirement for fasting, better tolerability, and less susceptibility to hepatic function variations, making it a promising alternative for these patients [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e]\\u003c/p\\u003e \\u003cp\\u003eThis study aimed to evaluate the efficacy and safety of switching from ELT or HET to AVA in treating pediatric ITP, providing clinical evidence and theoretical support for switching therapy in cases in which ELT or HET are ineffective or have lost efficacy.\\u003c/p\\u003e\"},{\"header\":\"Method\",\"content\":\"\\u003cp\\u003eThis multicenter, retrospective, observational cohort study was conducted in July 2024 and enrolled children with ITP treated with AVA at three referral children's hospitals in July 2024 to collect data from Aug 2021 to May 2024 (This study includes seven patients from the prior study[\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e]). For this retrospective study, ethics approval was obtained from the institutional review boards of Beijing Children\\u0026prime;s Hospital, Capital Medical University (Ethics approval NO. [2024]-Y-098-D). Informed consent was obtained from the patients and their guardians via telephone prior to the commencement of the study.\\u003c/p\\u003e \\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eInclusion and exclusion criteria\\u003c/h2\\u003e \\u003cp\\u003eInclusion criteria were as follows: 1) Aged 0 to 18 years diagnosed with ITP for more than three months; 2) lack of sustained response to first-line treatments (glucocorticoids, IVIG) with platelet counts below 30\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L and no response after treatment with ELT or HET; and 3) medication duration of at least two months and a total observation period exceeding two months.\\u003c/p\\u003e \\u003cp\\u003eThe exclusion criteria were as follows: 1) Diagnosis of secondary thrombocytopenia; 2) The legal guardian refused to participate in the study.\\u003c/p\\u003e \\u003cp\\u003e \\u003cb\\u003eDefinitions and outcomes\\u003c/b\\u003e[\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e]\\u003c/p\\u003e \\u003cp\\u003e\\u003col\\u003e\\u003cspan\\u003e\\u003cli\\u003e\\u003cp\\u003eResponse: a) Complete response (CR): Complete platelet response was defined as a platelet count of \\u0026ge;\\u0026thinsp;100\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L with no bleeding within two months. b) Response (R): Platelet response was defined as a platelet count of 30\\u0026ndash;100\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L, with at least a two-fold increase in platelet count from baseline and no bleeding within two months. c) No response (NR): platelet count\\u0026thinsp;\\u0026lt;\\u0026thinsp;30\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L, less than a two-fold increase from the baseline count, or bleeding after dose titration of AVA within two months. d) Overall response (OR): total number of patients who achieved CR and R.\\u003c/p\\u003e\\u003c/li\\u003e\\u003c/span\\u003e\\u003cspan\\u003e\\u003cli\\u003e\\u003cp\\u003eSustained response (SR): platelet count\\u0026thinsp;\\u0026gt;\\u0026thinsp;30\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L following an AVA dose at \\u0026ge;\\u0026thinsp;75% of the platelet count assessment at week 24 since the patient achieved a response.\\u003c/p\\u003e\\u003c/li\\u003e\\u003c/span\\u003e\\u003cspan\\u003e\\u003cli\\u003e\\u003cp\\u003eRescue therapy: Based on the clinical assessment, platelet transfusion or IVIG therapy was administered at the investigator\\u0026rsquo;s discretion. Rescue therapy was initiated when the platelet count dropped below 20\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L, and bleeding severity was graded as 3\\u0026ndash;4.\\u003c/p\\u003e\\u003c/li\\u003e\\u003c/span\\u003e\\u003cspan\\u003e\\u003cli\\u003e\\u003cp\\u003eBleeding grades.[\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e]: The Working Group of the Chinese Guidelines for the Diagnosis and Treatment of Childhood Primary Immune Criteria categorized bleeding into four grades (grade 0, no bleeding; grade 1, petechiae; grade 2, mild blood loss; grade 3, gross blood loss; and grade 4, debilitating blood loss)\\u003c/p\\u003e\\u003c/li\\u003e\\u003c/span\\u003e\\u003cspan\\u003e\\u003cli\\u003e\\u003cp\\u003eAdverse events (AEs): These were evaluated using the National Cancer Institute Common Toxicity Criteria, version 5.0 (CTCAE version 5.0). [\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e]. Thrombocytosis was defined as a platelet count of \\u0026ge;\\u0026thinsp;400\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L on one or more measurements using AVA.\\u003c/p\\u003e\\u003c/li\\u003e\\u003c/span\\u003e\\u003c/ol\\u003e\\u003c/p\\u003e \\u003cp\\u003eFollow-up protocol: Based on the severity of bleeding, Platelet count was required to be monitored weekly for the first month after AVA treatment and at least monthly thereafter.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec4\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStatistical analysis\\u003c/h2\\u003e \\u003cp\\u003eNormally and non-normally distributed continuous variables are shown as medians and quarters (Q1 and Q3), and non-normally distributed variables were analyzed using non-parametric \\u003cem\\u003et-tests\\u003c/em\\u003e (Mann\\u0026ndash;Whitney U test). Single-factor analysis was performed using the \\u003cem\\u003echi-square\\u003c/em\\u003e test or Fisher's exact probability test, with statistical significance set at a significance level of \\u003cem\\u003ep\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05. All analyses were performed using the GraphPad Prism 9.0.\\u003c/p\\u003e\"},{\"header\":\"Results \",\"content\":\"\\u003cp\\u003eA total of 67 patients with thrombocytopenia switched from ELT or HET to AVA. Among them, 6 patients were diagnosed with secondary ITP, four received AVA for less than 8 weeks, and two had newly diagnosed ITP. Ultimately, 55 patients were included in the study, comprising 46 who switched from ELT to AVA and 9 who switched from HET to AVA. \\u0026nbsp;(Figure 1)\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eGeneral characteristics of enrolled patients\\u0026nbsp;\\u003c/strong\\u003eBased on previous medications, patients were divided into the ELT-switch and HET-switch groups. The median diagnostic age of patients in the two groups was 4.3 years (2.2 years, 7.8 years) and three years (0.8 years, 6.3 years), respectively. Of the 55 patients, 30 were male, with 25 in the ELT-switch group and 5 in the HET-switch group. The median time from ITP diagnosis to the initiation of AVA was 1.9 years (1.0 years, 2.5 years) in the ELT-switch group and 0.9 years (0.2 years, 4.9 years) in the HET-switch group. In the ELT-switch group, 42 patients had received High-Dose dexamethasone (HDD) treatment, and 33 had undergone RTX therapy, compared to seven patients who had received HDD and four patients who had undergone RTX in the HET-switch group. The median duration of ELT treatment before switching to AVA was 4.8 months (2.3 months,12.9 months), and for HET, it was 2 months (2 months, 3.5 months). The median platelet count at the time of ITP diagnosis was 11\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L (5\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L, 19\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L) in the ELT switch group and 12\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L (4\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L, 16\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L) in the HET switch group, with no significant difference (\\u003cem\\u003ep\\u003c/em\\u003e\\u003cem\\u003e\\u0026nbsp;\\u003c/em\\u003e= 0.699). The median duration of AVA treatment post-switch was 12.9 months (6 months, 6.9 months) in the ELT-switch group and 8.6 months (4.6 months, 16.8 months) in the HET-switch group. All characteristics of patients in the ELT-switch and HET-switch groups showed no statistically significant differences (all\\u0026nbsp;\\u003cem\\u003ep\\u003c/em\\u003e\\u003cem\\u003e\\u0026nbsp;\\u003c/em\\u003e\\u0026gt; .05) (Table 1).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTable 1 Patient characteristics\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003ctable border=\\\"0\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"671\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 296px;\\\"\\u003e\\n \\u003cp\\u003eVariable\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 142px;\\\"\\u003e\\n \\u003cp\\u003eSwitch from ELT\\u003c/p\\u003e\\n \\u003cp\\u003e(n=46), %\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003eSwitch from HET\\u003c/p\\u003e\\n \\u003cp\\u003e(n=9), %\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cem\\u003ep\\u0026nbsp;\\u003c/em\\u003evalue\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 296px;\\\"\\u003e\\n \\u003cp\\u003eAge, median (IQR), year\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 142px;\\\"\\u003e\\n \\u003cp\\u003e4.3(2.2-7.8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e3(0.8-6.3)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e0.711\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 296px;\\\"\\u003e\\n \\u003cp\\u003eGender, male (n)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 142px;\\\"\\u003e\\n \\u003cp\\u003e25\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e5\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026gt;0.99\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 296px;\\\"\\u003e\\n \\u003cp\\u003eType of ITP (n)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 142px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 296px;\\\"\\u003e\\n \\u003cp\\u003epersistent ITP\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 142px;\\\"\\u003e\\n \\u003cp\\u003e12\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e0.422\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 296px;\\\"\\u003e\\n \\u003cp\\u003echronic ITP\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 142px;\\\"\\u003e\\n \\u003cp\\u003e34\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e5\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 296px;\\\"\\u003e\\n \\u003cp\\u003eTime since diagnosis, median (IQR), year\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 142px;\\\"\\u003e\\n \\u003cp\\u003e1.9(1.0-2.5)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e0.9(0.2-4.9)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e0.233\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 296px;\\\"\\u003e\\n \\u003cp\\u003eThe prior treatment before initiation of AVA\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 142px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 296px;\\\"\\u003e\\n \\u003cp\\u003ePrior HDD, n (%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 142px;\\\"\\u003e\\n \\u003cp\\u003e42(91.3%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e7(77.8%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e0.750\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 296px;\\\"\\u003e\\n \\u003cp\\u003ePrior RTX, n (%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 142px;\\\"\\u003e\\n \\u003cp\\u003e33(71.7%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e4(44.4%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 296px;\\\"\\u003e\\n \\u003cp\\u003eTime of TPO-RAs before initiation of AVA, median (IQR), month\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 142px;\\\"\\u003e\\n \\u003cp\\u003e4.8(2.3-12.9)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e2(2-3.5)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e0.079\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 296px;\\\"\\u003e\\n \\u003cp\\u003eDose of TPO-RAs before initiation of AVA, median (IQR), (mg/kg/d)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 142px;\\\"\\u003e\\n \\u003cp\\u003e1.3(1.1-1.7)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e0.13(0.11-0.14)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 296px;\\\"\\u003e\\n \\u003cp\\u003ePlatelet count diagnosed, median (IQR), (\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 142px;\\\"\\u003e\\n \\u003cp\\u003e11(5-19)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e12(4-16)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e0.699\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 296px;\\\"\\u003e\\n \\u003cp\\u003eFollow-up with AVA treatment, median (IQR), month\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 142px;\\\"\\u003e\\n \\u003cp\\u003e12.9(6-16.9)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e8.6(4.6-16.8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e0.445\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAbbreviation:\\u0026nbsp;\\u003c/strong\\u003eITP, Immune thrombocytopenia; ELT, eltrombopag; HET, hetrombopag;\\u003c/p\\u003e\\n\\u003cp\\u003eAVA, avatrombopag; HDD, high dose dexamethasone; RTX, rituximab.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eEfficacy\\u0026nbsp;\\u003c/strong\\u003eIn the ELT-switch group, 37 patients achieved an OR, including 28 who achieved a CR, while nine were classified as non-responders (NR). In the HET-switch group, six patients achieved OR, including four who achieved CR, and three were NR. No significant difference was observed between the two groups (\\u003cem\\u003ep\\u003c/em\\u003e\\u003cem\\u003e\\u0026nbsp;\\u003c/em\\u003e= 0.597). At six months, the sustained response (SR) rates were 48.4% (18/37) in the ELT-switch group and 33.3% (2/6) in the HET-switch groups, with no significant difference (\\u003cem\\u003ep\\u003c/em\\u003e = 0.668). The median effective AVA dosage was 0.73 mg/kg (0.63 mg/kg,\\u0026nbsp;0.86 mg/kg) in the ELT-switch group and 0.9 mg/kg (0.6 mg/kg, 1.0 mg/kg) in the HET-switch group, with no significant difference (\\u003cem\\u003ep\\u003c/em\\u003e = 0.174). In the ELT-switch group, 47.8% of the patients had a reduced AVA dosage compared with 33.3% in the HET-switch group, with no statistically significant difference (\\u003cem\\u003ep\\u0026nbsp;\\u003c/em\\u003e= 0.487) (Table 2). Baseline platelet counts were 18\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L (8\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L,\\u0026nbsp;26\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L) in the ELT-switch group and 19 \\u0026times; 10\\u003csup\\u003e9\\u003c/sup\\u003e/L (10\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L,\\u0026nbsp;28\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L) in the HET-switch group. After switching to AVA, the platelet count increased to 101\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L (46\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L, 175\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L) and 65\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L (31\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L, 99\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L) at 2 weeks, and to 110\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L (38\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L, 189\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L) and 101\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L (17\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L, 172\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L) at 2 months. At six months, the counts were 103\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L (40\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L, 210\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L) and 66\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L (40\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L, 97\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L), with no statistically significant differences between the groups at any time point (\\u003cem\\u003ep\\u0026nbsp;\\u003c/em\\u003e\\u0026gt;.05) (Figure 2).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTable 2 Efficacy of AVA treatment switch from ELT or HET on ITP\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003ctable border=\\\"0\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"575\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 187px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003eSwitch from ELT\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003eSwitch from HET\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 123px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cem\\u003ep\\u003c/em\\u003e value\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 187px;\\\"\\u003e\\n \\u003cp\\u003eResponse at eight weeks\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 187px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp; \\u0026nbsp; CR, n (%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e28(60.8%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e4(44.4%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 187px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp; \\u0026nbsp; R, n (%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e9(19.6%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e2(22.3%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e\\n \\u003cp\\u003e0.597\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 187px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp; \\u0026nbsp; NR, n (%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e9(19.6%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e3(33.3%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 187px;\\\"\\u003e\\n \\u003cp\\u003eSR\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e18/37(48.4%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e2/6(33.3%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e\\n \\u003cp\\u003e0.668\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 187px;\\\"\\u003e\\n \\u003cp\\u003eTTR\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e10(5,17)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e7(5,14)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e\\n \\u003cp\\u003e0.402\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 187px;\\\"\\u003e\\n \\u003cp\\u003eEffective AVA dose, mg/kg/d\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e0.73(0.63,0.86)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e0.90(0.60,1.0)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e\\n \\u003cp\\u003e0.174\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 187px;\\\"\\u003e\\n \\u003cp\\u003eTaper of AVA\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e22/46\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e3/9\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e\\n \\u003cp\\u003e0.487\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAbbreviation:\\u003c/strong\\u003e CR, complete response; R, response; NR, no response; SR, sustained response; TTR, time to response; ELT, eltrombopag; HET, hetrombopag; AVA, avatrombopag.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eBleeding improvement\\u0026nbsp;\\u003c/strong\\u003eAt baseline, 69% of the patients (32/46) in the ELT-switch group and 77% of the patients (7/9) in the HET-switch group had bleeding symptoms, including 18 with grade 1, 8 with grade 2, 7 with grade 3, and 1 with grade 4 bleeding in the ELT-switch group, and 4 with grade 1 and 3 with grade 2 bleeding. After one month, three patients had grade 1 bleeding, and two had grade 2 bleeding. After one month of treatment, the number of patients with bleeding decreased to 26% (12/46) and 55% (5/9). After nine or eight months, all bleeding symptoms resolved in both groups (Figure 3).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConcomitant medication and rescue therapy\\u0026nbsp;\\u003c/strong\\u003eAt baseline, 36.9% of patients (17/46) in the ELT-switch group and 21.7% of patients (10/46) in the HET-switch group were on concomitant medication, which decreased to 6.5% (3/46) and 11.1% (1/9), respectively. After following for 12 months, the concomitant medication in the ELT-switch group and HET-switch group was decreased to 12.5% and 0, respectively. (Figure 4A). At baseline, 21.7% of patients (10/46) in the ELT-switch group and 22.2% (2/9) in the HET-switch group required rescue therapy. After one month, the rescue therapy rate decreased to 6.5% (3/46) and 11.1% (1/9), respectively. After following for 12 months, the rescue therapy in the ELT-switch group and HET-switch group was decreased to 6% and 0, respectively. \\u0026nbsp;(Figure 4B).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTRAEs\\u0026nbsp;\\u003c/strong\\u003eThe most common treatment-related adverse event was an elevated platelet count, which occurred in 19/46 (41.3%) patients in the ELT-switch group and 3/9 (33.3%) patients in the HET-switch group; no thrombotic complications occurred during the treatment. In the ELT group, five patients (10.8%) experienced gastrointestinal symptoms such as vomiting and diarrhea, and two patients (4.3%) reported headaches, with one patient (2.1%) feeling fatigued after taking the medication. One patient (11.1%) in the HET group developed gastrointestinal symptoms. (Table 3).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTable 3\\u003c/strong\\u003e \\u003cstrong\\u003eTreatment-related adverse events\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003ctable border=\\\"0\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 165px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 175px;\\\"\\u003e\\n \\u003cp\\u003eSwitch from ELT,(n=46), %\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 185px;\\\"\\u003e\\n \\u003cp\\u003eSwitch from HET,(n=9), %\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 165px;\\\"\\u003e\\n \\u003cp\\u003ePlatelet elevation\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 175px;\\\"\\u003e\\n \\u003cp\\u003e19(41.3%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 185px;\\\"\\u003e\\n \\u003cp\\u003e3(33.3%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 165px;\\\"\\u003e\\n \\u003cp\\u003eGastrointestinal reactions\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 175px;\\\"\\u003e\\n \\u003cp\\u003e59(10.9%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 185px;\\\"\\u003e\\n \\u003cp\\u003e1(11.1%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 165px;\\\"\\u003e\\n \\u003cp\\u003eHeadache\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 175px;\\\"\\u003e\\n \\u003cp\\u003e2(4.3%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 185px;\\\"\\u003e\\n \\u003cp\\u003e0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 165px;\\\"\\u003e\\n \\u003cp\\u003eFatigue\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 175px;\\\"\\u003e\\n \\u003cp\\u003e1(2.2%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 185px;\\\"\\u003e\\n \\u003cp\\u003e0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eTPO-RAs, including small molecules such as ELT, HET, and AVA, have been widely used as second-line treatments for pediatric ITP because of their sustained efficacy and favorable safety profiles. These drugs activate the Janus kinase-signal transducers and activators of transcription (JAK-STAT) and mitogen-activated protein kinase (MAPK) signaling pathways by binding to the thrombopoietin receptor, stimulating megakaryocyte proliferation, and increasing platelet count [13].\\u0026nbsp;Hetrombopag, the first small-molecule, non-peptide oral TPO-RA developed in China, has demonstrated significant efficacy in a randomized, multicenter, placebo-controlled Phase III trial. The study revealed that compared to placebo, HET significantly increased platelet counts and reduced the risk of bleeding[14].\\u0026nbsp;Clinical studies have shown that TPO-RAs, including small molecules such as ELT and HET and giant peptide drugs such as romiplostim, are both safe and effective in treating pediatric ITP\\u0026nbsp;[13].\\u003c/p\\u003e\\n\\u003cp\\u003eThough ELT and HET have demonstrated efficacy in both persistent ITP and chronic ITP, patients may develop \\u0026quot;off response\\u0026quot; over time, necessitating a switch to other treatments. The PETIT study demonstrated that 81% of children achieved platelet counts of \\u0026ge; 50 \\u0026times; 10⁹/L within 24 weeks of ELT treatment[15] and PETIT 2 reported an 80% OR rate after 24 weeks.[16] However, long-term studies by Wang et al. reported that 18.6% of patients required a switch to another therapy because of a loss of response. [17]. A few patients regained their response to ELT after a break. In contrast, for treatment failures, it is necessary to initiate treatment with other TPO-RAs, such as romiplostim, or alternative therapies, such as daratumumab or\\u0026nbsp;RTX, to achieve better management of the condition.[18].\\u0026nbsp;Our previous study observed that patients with failed ELT responded well to AVA, with an OR rate of 81.8% and a CR rate of 54.6%.[9].\\u003c/p\\u003e\\n\\u003cp\\u003eAVA, a second-generation TPO-RA, offers advantages over first-generation drugs, such as ELT and HET. AVA does not need to be administered on an empty stomach, carries no risk of iron deficiency anemia with AVA and no known hepatotoxicity signal, and has potent platelet-elevating effects that make it suitable for perioperative thrombocytopenia management. [6]. Pharmacokinetically, AVA reaches its peak plasma concentration 6\\u0026ndash;8 h post-administration and has a half-life of approximately 19 h, and its efficacy in treating thrombocytopenia in chronic liver disease and in perioperative settings has been validated in ADAPT-1 and ADAPT-2 studies, with 90% of patients avoiding platelet transfusions or rescue therapies during the perioperative period.[19]. Additionally, a multicenter study showed that 79.4% of children achieved OR within four weeks of AVA treatment.[20]. In adult ITP patients who switched to AVA due to the ineffectiveness of ELT or romiplostim, a median follow-up duration of 9.2 months was achieved, demonstrating favorable efficacy and tolerability,\\u0026nbsp;with\\u0026nbsp;93% achieving an OR, and 86% achieving CR.\\u0026nbsp;[21].\\u0026nbsp;Unlike the previous study, in which patients switched to AVA for various reasons, including adverse events and convenience, all patients in our study switched because of treatment failure or loss of response.\\u003c/p\\u003e\\n\\u003cp\\u003eIn our study, the OR for the ELT and HET switch groups after transitioning to AVA were 82.6% and 80%, respectively, with CR rates of 65.2% and 60%. No significant differences were observed between the groups (\\u003cem\\u003ep\\u0026nbsp;\\u003c/em\\u003e\\u0026gt; 0.05), suggesting that AVA maintains its efficacy in treating ITP when transitioning from ELT or HET. These findings are consistent with those of our earlier study, which showed an OR rate of 81.8% and a\\u0026nbsp;CR rate of 54.6% in patients who switched from ELT to AVA. [9].\\u003c/p\\u003e\\n\\u003cp\\u003eFurthermore, significant improvements in bleeding were observed after switching to AVA, with the proportion of patients experiencing bleeding decreasing from approximately 70% at baseline to nearly 0% at 8\\u0026ndash;9 months post-treatment. Concurrent medication use and rescue therapies decreased in patients who responded to AVA, which is consistent with the results of previous studies. [20].\\u003c/p\\u003e\\n\\u003cp\\u003eIn both groups, platelet counts peaked 1\\u0026ndash;2 weeks after the start of AVA. In the larger ELT-switch group, platelet counts reached their peak two weeks post-treatment before stabilizing, consistent with Al-Samkari\\u0026apos;s[21] findings, which attributed the peak to a \\u0026quot;first dose effect\\u0026quot; of AVA, which promotes anti-apoptotic activity in megakaryocytes.\\u003csup\\u003e\\u0026nbsp;\\u003c/sup\\u003e\\u003csup\\u003e\\u0026nbsp;\\u003c/sup\\u003e[22].\\u0026nbsp;The most common AE observed with AVA was thrombocytosis, which occurred in 41.3% of the patients in the ELT-switch group and 30% in the HET-switch group. Unlike adults, where AVA-associated thrombocytosis is linked to thromboembolic events or bone marrow fibrosis,[6, 23, 24],\\u0026nbsp;pediatric patients mainly experience thrombocytosis without thrombotic complications, likely due to the lower prevalence of comorbid conditions such as hyperlipidemia and hyperglycemia.\\u0026nbsp;Other common AEs included gastrointestinal symptoms (abdominal pain, diarrhea, and vomiting), which occurred in 10.8% and 10% of the patients in the ELT and HET switch groups, respectively. Additionally, 4.2% and 2.1% of patients in the ELT group experienced headaches and fatigue, respectively. These AEs were not observed in the HET group, potentially because of the small sample size. Previous studies have identified headache as a common AE, occurring in 2 out of 12 patients who discontinued AVA owing to severe AEs.[25]\\u0026nbsp;.\\u0026nbsp;In our study, two patients reported mild headaches, but no severe AEs were observed. None of the severe AEs commonly reported in adult studies, such as thromboembolism, occurred in the pediatric cohort.[23, 24].\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eTo our knowledge, this is the first large-scale, multicenter study to examine the efficacy and safety of switching to TPO-RAs in Chinese children with ITP. However, this study had several limitations. First, this was a retrospective analysis, and future prospective studies are required. Second, the HET-switch group had a smaller sample size, likely because of the relatively recent introduction of the HET. Future studies should aim to include larger sample sizes and conduct long-term, multicenter, prospective cohort studies.\\u003c/p\\u003e\\n\\u003cp\\u003eAVA has shown great potential as a second-line treatment for pediatric ITP, with promising results for both persistent ITP and chronic ITP. Reports of its effectiveness exist in adult NITP, further supporting the potential of AVA for broader applications. Although AVA has demonstrated good efficacy and safety, its high cost presents a financial burden compared to ELT and HET, which may limit its use. Families who can afford AVA may be the preferred second-line treatment for pediatric ITP.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eACKNOWLEDGEMENTS\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors thank the patients, their families, and all investigators involved in this study, including physicians and laboratory technicians.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCONFLICT OF INTEREST STATEMENT\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors declare that they have no potential conflicts of interest.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eDATA AVAILABILITY STATEMENT\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eDue to the nature of this research, the participants did not agree for their data to be shared publicly; therefore, supporting data are not available. Further inquiries can be directed to the corresponding authors.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFUNDING INFORMATION\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis work was supported by funding from the Reform and Development of the Beijing Municipal Health Commission, Capital\\u0026apos;s Funds for Health Improvement and Research (No. 2022-2Z-2099), the Beijing Municipal Administration of Hospitals Incubating Program (No. PX2023044) and National Natural Science Foundation of China (No.81970111). This work was supported in part by grants from the Beijing Municipal Administration of Hospitals Incubating Program (No. PX2022051).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAUTHOR CONTRIBUTIONS\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eRunhui Wu and Xiaoling Cheng designed the research. All authors performed the research and collected data. Jingjing Liu interpreted the data and wrote the manuscript. Zhifa Wang, Nan Wang, and Jingyao Ma analyzed the data. Lijuan Wang and Yan Liu participated in data collection. Jinxi Meng and Shuyue Dong completed Figure 1 and Figure 2. Yu Hu and Juntao Ouyang completed Figure 3. Zhenping Chen participated in data analysis. All authors read and approved the final version of this manuscript.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eGonzalez-Lopez, T.J., et al., Primary and secondary immune thrombocytopenia (ITP): Time for a rethink. Blood Rev, 2023. 61: p. 101112.\\u003c/li\\u003e\\n\\u003cli\\u003eSemple, J.W., et al., An update on the pathophysiology of immune thrombocytopenia. Curr Opin Hematol, 2020. 27(6): p. 423-429.\\u003c/li\\u003e\\n\\u003cli\\u003eLo, E. and S. Deane, Diagnosis and classification of immune-mediated thrombocytopenia. Autoimmun Rev, 2014. 13(4-5): p. 577-83.\\u003c/li\\u003e\\n\\u003cli\\u003eNeunert, C., et al., American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv, 2019. 3(23): p. 3829-3866.\\u003c/li\\u003e\\n\\u003cli\\u003eProvan, D., et al., Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv, 2019. 3(22): p. 3780-3817.\\u003c/li\\u003e\\n\\u003cli\\u003eMarkham, A., Avatrombopag: A Review in Thrombocytopenia. Drugs, 2021. 81(16): p. 1905-1913.\\u003c/li\\u003e\\n\\u003cli\\u003eOladapo, A., et al., Avatrombopag treatment response in patients with immune thrombocytopenia: the REAL-AVA 1.0 study. Ther Adv Hematol, 2023. 14: p. 20406207231179856.\\u003c/li\\u003e\\n\\u003cli\\u003eSyed, Y.Y., Hetrombopag: First Approval. Drugs (New York, N.Y.), 2021. 81(13): p. 1581-1585.\\u003c/li\\u003e\\n\\u003cli\\u003eCheng, X., et al., Outcomes of switching to avatrombopag following treatment failure with eltrombopag in paediatric immune thrombocytopenia: A real-world study in China. Br J Haematol, 2023. 202(3): p. 636-644.\\u003c/li\\u003e\\n\\u003cli\\u003eWorking Group On The Adaptation Of Guidelines For The Diagnosis And Treatment Of Primary Immune Thrombocytopenia In Chinese Children, Paediatrics Hematology Group Of The Chinese Medical Association and E.B.O.T. Pediatrics, Adapted guideline for the diagnosis and treatment of primary immune thrombocytopenia for Chinese children (2021). Chin J Pediatr, 2021. 59(10): p. 810-819.\\u003c/li\\u003e\\n\\u003cli\\u003eCommon Terminology Criteria for Adverse Events (CTCAE) Version 5.0.\\u003c/li\\u003e\\n\\u003cli\\u003eNeunert, C., et al., The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood, 2011. 117(16): p. 4190-207.\\u003c/li\\u003e\\n\\u003cli\\u003eGilreath, J., M. Lo and J. Bubalo, Thrombopoietin Receptor Agonists (TPO-RAs): Drug Class Considerations for Pharmacists. Drugs, 2021. 81(11): p. 1285-1305.\\u003c/li\\u003e\\n\\u003cli\\u003eMei, H., et al., A multicenter, randomized phase III trial of hetrombopag: a novel thrombopoietin receptor agonist for the treatment of immune thrombocytopenia. J Hematol Oncol, 2021. 14(1): p. 37.\\u003c/li\\u003e\\n\\u003cli\\u003eBussel, J.B., et al., Eltrombopag for the treatment of children with persistent and chronic immune thrombocytopenia (PETIT): a randomised, multicentre, placebo-controlled study. Lancet Haematol, 2015. 2(8): p. e315-25.\\u003c/li\\u003e\\n\\u003cli\\u003eGrainger, J.D., et al., Eltrombopag for children with chronic immune thrombocytopenia (PETIT2): a randomised, multicentre, placebo-controlled trial. Lancet, 2015. 386(10004): p. 1649-58.\\u003c/li\\u003e\\n\\u003cli\\u003eWang, Z., et al., Long-term eltrombopag in children with chronic immune thrombocytopenia: A single-centre extended real-life observational study in China. Br J Haematol, 2024. 204(3): p. 1017-1023.\\u003c/li\\u003e\\n\\u003cli\\u003eCooper, N., et al., Real-world use of thrombopoietin receptor agonists for the management of immune thrombocytopenia in adult patients in the United Kingdom: Results from the TRAIT study. British journal of haematology, 2024. 204(6): p. 2442-2452.\\u003c/li\\u003e\\n\\u003cli\\u003eTerrault, N., et al., Avatrombopag Before Procedures Reduces Need for Platelet Transfusion in Patients With Chronic Liver Disease and Thrombocytopenia. Gastroenterology, 2018. 155(3): p. 705-718.\\u003c/li\\u003e\\n\\u003cli\\u003eWang, Z., et al., Efficacy and safety of avatrombopag in Chinese children with persistent and chronic primary immune thrombocytopenia: A multicentre observational retrospective study in China. Br J Haematol, 2024. 204(5): p. 1958-1965.\\u003c/li\\u003e\\n\\u003cli\\u003eAl-Samkari, H., et al., Adults with immune thrombocytopenia who switched to avatrombopag following prior treatment with eltrombopag or romiplostim: A multicentre US study. Br J Haematol, 2022. 197(3): p. 359-366.\\u003c/li\\u003e\\n\\u003cli\\u003eAl-Samkari, H. and S. Nagalla, Efficacy and safety evaluation of avatrombopag in immune thrombocytopenia: analyses of a phase III study and long-term extension. Platelets, 2022. 33(2): p. 257-264.\\u003c/li\\u003e\\n\\u003cli\\u003eTarantino, M.D., et al., A phase 3, randomized, double-blind, active-controlled trial evaluating efficacy and safety of avatrombopag versus eltrombopag in ITP. Br J Haematol, 2023. 202(4): p. 897-899.\\u003c/li\\u003e\\n\\u003cli\\u003eBussel, J.B., et al., A randomized trial of avatrombopag, an investigational thrombopoietin-receptor agonist, in persistent and chronic immune thrombocytopenia. Blood, 2014. 123(25): p. 3887-94.\\u003c/li\\u003e\\n\\u003cli\\u003eBiovitrum., S.O., DOPTELET\\u0026reg;(avatrombopag): US prescribing information. 2020: p. Accessed 17 Sep 2021.\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":true,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"annals-of-hematology\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"aohe\",\"sideBox\":\"Learn more about [Annals of Hematology](http://link.springer.com/journal/277)\",\"snPcode\":\"277\",\"submissionUrl\":\"https://submission.nature.com/new-submission/277/3\",\"title\":\"Annals of Hematology\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"stoa\",\"reportingPortfolio\":\"Springer Hybrid\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":false},\"keywords\":\"immune thrombocytopenia, thrombopoietin receptor agonists, eltrombopag, hetrombopag, avatrombopag\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-6187960/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-6187960/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003eAvatrombopag (AVA), a second-generation thrombopoietin receptor agonist (TPO-RA), has demonstrated efficacy in pediatric persistent/chronic immune thrombocytopenia (ITP). However, critical evidence gaps persist regarding treatment-switching strategies between TPO-RAs, particularly when transitioning from eltrombopag (ELT) or hetrombopag (HET) to AVA. This multicenter cohort study evaluated 55 pediatric ITP patients unresponsive to or relapsing after ELT (n\\u0026thinsp;=\\u0026thinsp;46) or HET (n\\u0026thinsp;=\\u0026thinsp;9) who underwent AVA switch therapy. Outcomes included platelet response (\\u0026ge;\\u0026thinsp;30\\u0026times;10⁹/L without rescue therapy), bleeding events, concomitant medication reduction, and safety. Sustained response rates reached 48.4% (ELT-to-AVA) and 33.3% (HET-to-AVA), with median response durations of 10 and 7 days respectively. Platelet elevation during AVA treatment was resolved with dosage changes or discontinuation. AVA significantly reduced bleeding, ITP medications, and rescue therapy, with side effects such as gastrointestinal symptoms, headaches, and fatigue (grades 1\\u0026ndash;2). AVA demonstrates potential as a safe and effective bridging therapy for TPO-RA refractory pediatric ITP, offering hematological stabilization while reducing treatment burden. These findings address current evidence deficiencies in TPO-RA switching protocols.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Multicenter, Real-World Observational Study of AVA Therapy Following ELT/HET Switching in Chinese Children with Persistent/Chronic Primary ITP\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-03-27 07:59:42\",\"doi\":\"10.21203/rs.3.rs-6187960/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"decision\",\"content\":\"Revision requested\",\"date\":\"2025-07-10T07:40:40+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2025-07-09T19:39:25+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"68318790865604522627627700066560805020\",\"date\":\"2025-06-29T14:39:45+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"231966370016904821073337588966519462644\",\"date\":\"2025-04-06T05:16:43+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2025-03-31T13:38:04+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"20826201324356840671211663140739742520\",\"date\":\"2025-03-28T13:50:21+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewersInvited\",\"content\":\"\",\"date\":\"2025-03-18T07:49:25+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2025-03-13T12:56:53+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"checksComplete\",\"content\":\"\",\"date\":\"2025-03-13T12:52:49+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"Annals of Hematology\",\"date\":\"2025-03-09T09:49:33+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"annals-of-hematology\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"aohe\",\"sideBox\":\"Learn more about [Annals of Hematology](http://link.springer.com/journal/277)\",\"snPcode\":\"277\",\"submissionUrl\":\"https://submission.nature.com/new-submission/277/3\",\"title\":\"Annals of Hematology\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"stoa\",\"reportingPortfolio\":\"Springer Hybrid\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":false}}],\"origin\":\"\",\"ownerIdentity\":\"4e530942-1279-4df0-b0eb-5c85118315ce\",\"owner\":[],\"postedDate\":\"March 27th, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"published-in-journal\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2025-09-15T16:01:32+00:00\",\"versionOfRecord\":{\"articleIdentity\":\"rs-6187960\",\"link\":\"https://doi.org/10.1007/s00277-025-06567-9\",\"journal\":{\"identity\":\"annals-of-hematology\",\"isVorOnly\":false,\"title\":\"Annals of Hematology\"},\"publishedOn\":\"2025-09-11 15:56:57\",\"publishedOnDateReadable\":\"September 11th, 2025\"},\"versionCreatedAt\":\"2025-03-27 07:59:42\",\"video\":\"\",\"vorDoi\":\"10.1007/s00277-025-06567-9\",\"vorDoiUrl\":\"https://doi.org/10.1007/s00277-025-06567-9\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-6187960\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-6187960\",\"identity\":\"rs-6187960\",\"version\":[\"v1\"]},\"buildId\":\"XKTyCvWXoU3ODBz1xrDgd\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}