Citations

Abstract Use of Direct oral anticoagulants (DOAC) has increased exponentially since their introduction in 2010. Over the years they have been used without any systematic oversight, there have been ongoing concerns related to inappropriate or incorrect dosing, incorrect duration, and non-adherence to the drugs leading to adverse patient outcomes. Several factors have been attributed to DOAC non-adherence such as presence or fear of adverse effects, affordability, lack of perceived benefit, or concerns for reversibility. These barriers impact both primary (first time prescription) and secondary adherence (longer term prescription). Poor adherence can lead to adverse outcomes such as stroke, death, and higher medical resource utilization hence increased cost to the patient and payors. This study was conducted as a quality improvement (QI) initiative to improve the adherence to the prescription DOACS. We included patients 18 years old, a diagnosis of Atrial fibrillation and flutter who had a primary care provider writing the prescription for chronic DOAC therapy. Patients with venous thrombosis, pregnancy or who were institutionalized were excluded. The charts were reviewed for primary and secondary adherence using Surescripts functionality which can provide baseline information about prescription fills from the participating pharmacies. In the preimplementation phase we identified 1030 patients meeting inclusion criteria associated with the pilot sites within Mayo Clinic practice in preceding 6 months. For this population, Surescripts data found that the rates of primary and secondary adherence to be 84% and 86% respectively. We then implemented a 6-month pilot where we created workflow for a pharmacy led DOAC management unit. Herein, once a DOAC prescription was made for patients meeting inclusion criteria, they would enter a registry where the pharmacy team would review the charts for primary adherence by utilizing Surescripts data. If adherent these patients would be marked for follow up in the secondary adherence phase. However, if non adherent, the team would initiate intervention including engagement with patient online services which was further escalated to phone calls by the pharmacy team. Once the barriers were identified several remediation approaches were incorporated in the process, these included education about DOACS, medicare education, social work assistance to even switching to warfarin if necessary. The same process was followed for secondary adherence management. In the intervention cohort, we had 411 patients during the pilot, for primary adherence 87.1% of patients were adherent at baseline and an additional 3.4% became adherent with interventions, while 9.5% remain nonadherent. The primary causes of nonadherence, amongst 9.5%, were cost (86%) while 1% were concerned about side effects and 3% were concerned about lack of perceived benefit. The inverntions lead to impoved adherence in most patients and very few patients were transitioned to warfarin. For secondary adherence 92% of the patients were adherent without any intervention, an additional 4% of patients benefited with the interventions of the DOAC management unit with approaches to address cost considerations, while another 4% remained nonadherent where cost remained the primary reason for nonadherence, other reasons being lack of perceived benefit and side effect concerns. In summary, with active intervention, in our patient population we were able to improve the primary adherence from 84% to 91% and secondary adherence from 86% to 96% . Cost remained the biggest barrier for adherence followed by concern for side effects and lack of perceived benefit. Our engaged team of pharmacy staff was able to manage those concerns with the education and cost mitigation strategies leading to improved adherence. Based on previously published literature even a 5% difference in adherence to DOACS can make a huge difference in population-based outcomes. Our work was able to demonstrate a positive impact of the intervention, highlighting the need for a well-managed DOAC unit especially for complex care populations.

Abstract Introduction: Warm autoimmune hemolytic anemia (wAIHA) is a rare, life-threatening, relapsing, autoantibody-driven disease associated with a significant physical, emotional, and quality of life burden on patients and caregivers. In rare diseases like wAIHA, patients more often rely on publicly available online disease information to improve their health literacy, however available data and educational resources on the internet are often limited. Rapidly evolving technology has led to a rise in patients and care partners utilizing online digital health resources to gather information and seek support. Developing patient-facing educational materials in collaboration with the end user may help increase utilization and engagement, which would facilitate improving patient health. This qualitative patient research aimed to gather feedback from individuals living with wAIHA on creative concepts for a disease state education website and to gain insight on proposed content areas for the educational resource. Methods: A wAIHA patient council was convened to better understand the perspective of individuals living with wAIHA. US-based adults with a self-reported diagnosis of wAIHA who were members of the patient council participated in a 2-hour virtual focus group to discuss a wAIHA disease state education website concept and provide insight into potential gaps in patient education. Participants were permitted to provide feedback in an online questionnaire as an alternative to joining the session. The session focused on reviewing the website design concept and four proposed content areas. Focus group discussions were audio-recorded and transcribed. Transcripts were qualitatively analyzed to identify key themes and insights. Results: Four individuals living with wAIHA participated in the virtual focus group and one gave feedback via the online survey. Most participants were female (80%) and White (60%). Participants expressed an unmet need for a reliable and easy to understand educational website that could be utilized by patients, care partners, and their loved ones throughout the wAIHA journey. The most important information for the wAIHA educational website, as identified by participants, included disease state information (ranging from basic disease explanations/definitions to comprehensive data on the disease), resources for patient support groups, and patient testimonials. Proposed content areas included suspected wAIHA, understanding wAIHA, living with wAIHA, and resources and support; these were all deemed valuable by participants. They recommended enhancements like creating a dedicated section for family and care partners, offering guidance on parenting with wAIHA, and providing further explanations of disease-related terms and resources. Insights gathered on the initial website design concept provided actionable changes to content such as alternative imagery to emphasize the wAIHA community and refinement of text to reinforce the website as a guiding tool for patients and care partners. Participant feedback was incorporated into the final concept resulting in a patient-centered digital resource. Conclusions: Including perspectives of individuals living with wAIHA in the development of patient-facing educational resources is key to creating impactful tools for the intended user. Insights collected from this exploratory research directly contributed to the improvement of the concept for a wAIHA disease state education website, making it more engaging and impactful. This research demonstrates the value of focus groups in gaining insight into patient preferences for educational resources and guiding their development to be customized for the end user.

Abstract BackgroundWarm autoimmune hemolytic anemia (wAIHA) is clinically characterized by autoantibody-mediated (typically IgG) erythrocyte destruction at body temperature. While oral corticosteroids remain first-line therapy, rituximab is frequently used as a second-line agent, mostly supported with concomitant background medications, yet real-world evidence is limited and utilization is driven by published retrospective data and expert opinion. Real-world evidence characterizing its utilization patterns and outcomes is needed to inform clinical practice. AimsThis study aimed to: 1) describe treatment patterns among patients with newly diagnosed wAIHA, 2) evaluate rescue therapy use and healthcare resource utilization (HCRU) with current standard of care (SOC), 3) characterize patterns of rituximab use during the first year. MethodsNewly diagnosed wAIHA patients were identified from multiple US databases (MarketScan® Databases, IQVIA PharMetrics, Optum Clinformatics®, and Optum PanTher EHR). Patients with ≥1 wAIHA diagnosis code in any position (ICD-10-CM D59.11) from October 2020 to December 2023 and 12-month post-index follow-up were pooled together. Secondary wAIHA was defined with evidence of hematologic malignancy, solid tumors, immunodeficiencies, or autoimmune diseases in the 6 months prior to diagnosis. Patients on treatment were defined by use of oral corticosteroids (OCS), immunosuppressants (IST) (including azathioprine, mycophenolate mofetil, cyclosporine, cyclophosphamide, or tacrolimus) or rituximab. Initial therapy was defined as the first treatment occurring ≥ 30 days prior to diagnosis. Therapies were identified as combination when initialized within 21 days of each other. The regimen is considered active until all therapies are discontinued or a new agent is initiated. Rituximab regimens were classified as standard (4 weekly doses), alternative (2 doses given 2 weeks apart), single infusion, or extended (>4 infusions). Results Among 2,028 wAIHA patients (median age 62.0 years, 59% female), 55% had secondary wAIHA. Among patients on treatment (n=1,439), 64% received OCS monotherapy; rituximab and IST, alone or in combination with OCS were received by an additional 28% and 5% of patients, respectively. Overall, 80% of treated patients received OCS in some combination during initial therapy. Within 12 months following diagnosis, 1 in 4 patients required ≥ 1 blood transfusion, 1 in 8 required either erythropoiesis-stimulating agents (ESA) or intravenous immunoglobulin (IVIG). Within 12 months of diagnosis, 35% of patients required ≥ 1 hospitalization, average length of stay 3.8 days; AIHA was the principal diagnosis for 65% cases. Greater than 1/3 of patients (38%) had ≥ 1 emergency department visit. Almost all wAIHA patients (98%) had an all-cause outpatient visit with a median of 31 visits per patient. Among patients receiving rituximab in any line (n=613), median time from diagnosis to first administration was 59.0 days (interquartile range: 42.0-171.0). For the first course of rituximab, 62.2% of patients received a complete course (standard, alternative, or extended courses). Among patients with a completed course, 39.8% had >4 infusions without a 90-day gap between administrations with a median of 8 administrations within 12 months. Of the nearly 38% of patients that did not receive a complete course of rituximab, 33% received a single infusion. The use of rescue medications in the period prior to rituximab treatment was compared to the period after treatment (defined as 60 days to 12-months post final rituximab infusion). Use of blood transfusions was observed to increase from 9.0% to 32.8%, while the use of ESA and IVIG were stable at approximately 2% and 4%, respectively.Conclusion With current wAIHA SOC, US HCRU remains high, posing a financial burden in terms of the rate of outpatient and emergency department visits, and inpatient stays. Rituximab is an early line therapy post-diagnosis, typically in combination with OCS. No changes in rescue treatments, and an increase in blood transfusions after rituximab infusion suggest treatment gaps remain. Analysis reveals heterogeneity in rituximab dosing patterns including high deviation from standard dosing practices; this variance from published expert opinion along with common use of rescue therapies suggests continued need for standardized guidelines and development of targeted therapies in wAIHA.

Abstract Gentically driven classical hematological disorders have variable prevelance in the general population, sickle cell disease (SCD) being the most common at 30 per 100,000 people, hemophilia (hem) 12 per 100,000 people for hemophilia A, 4 per 100,000 people for hemophilia B, and thalassemia (thal) at 18 per 100,000 people, with regional and racial-ethnic variation across US. There has been a dramatic change in the therapeutic landscape for these diseases in the past decade. Several new drugs and biological therapies including gene therapies have been approved for each of these disorders. Clinicians utilize different information sources to assimilate this rapid influx of knowledge into their practice; in the era of social media, the readership is not limited to original publications. As research visibility influences clinical adoption and patient awareness, it is vital to understand the modalities of engagement of gene therapy studies by clinicians and patients. An altmetric score is a simple and effective way of understanding engagement with research across platforms. It. measures digital attention received by research output, allowing us to gauge the social impact of an article. We sought to compare the impact and scientific dissemination of publications of gene therapy trials in these 3 diseases by capturing the number of traditional citations and Altmetric assessment score. Methods: A PubMed search was conducted for gene therapy trials in SCD, Hem and Thal between 2015 to 2025 and citations were captured using metrics from Google Scholar. The Altmetric assessment score for each article was determined using www.altmetric.com which includes any mention by news outlets, blogs, Twitter (X), Facebook, and Mendeley reader counts. Descriptive statistics are reported for the number of citations as well as the Altmetric assessment score in each of the disease categories. Median and range were reported due to the skewed distribution of the data. Comparison across groups for significance was done using the Kruskal-Wallis test. Results: The number of qualifying studies for SCD (n=7) were lower than hem (n=21) and thal (n=12). Median PubMed citations were highest for SCD (147, range 4-436), followed by hem (26, range 0-828) and thal (42, range 0-801), though the difference was not statistically significant (p=0.4) Altmetric scores demonstrated differences that approached statistical significance with p=0.08: SCD had the highest median (422, range 4-770), driven by exceptional Twitter engagement, while hem and thal medians were 20 (range 0-2038) and 49 (range 0-825) respectively. Twitter/X was the leading social platforms for all diseases. Scholarly interest measured by Mendeley readers was also highest for SCD (median 195, range 11-542), with thal and hem medians at 50 (range 0-773) and 64 (range 8-646) respectively. Conclusion: We observed substantial variability in both academic and social media dissemination of practice-changing SCD, Hem and thal gene therapy studies, though not statistically significant likely due to the limited number of studies overall. Higher citation count and Altmetric score in SCD studies may reflect recent robust dissemination efforts by ASH and patient advocacy groups. Intentional promotion across academic and media platforms increases awareness, helping with early dissemination of updated information that could have significant impact on patient outcomes.

Abstract Introduction A 2017 survey by the American Society of Hematology found a widespread perceived shortage of classical hematologists in the US, which was compounded by a low trainee interest in the field (<5%) (Masselink LE, Blood Adv 2019). Recently, we reported that among hematologist/oncologists at the 64 National Cancer Institute (NCI)-designated cancer centers with clinical programs, only ~5% identify as classical hematologists, despite 15% of them including classic hematology (CH) patients in their practice (Go LT, Blood Adv, in press). However, there remains limited data on CH consult volumes at NCI-designated cancer centers (West CV, JCO Oncol Pract 2023). This study aimed to evaluate the volume and nature of CH outpatient consults at the Mayo Clinic Comprehensive Cancer Center (MCCC). Methods We reviewed electronic medical records to identify all completed outpatient consults in CH, malignant hematology (MH), and solid tumor oncology at MCCC in Rochester, Minnesota from January 1 to December 31, 2024. Consults were defined as either external or internal referrals for new patients seen in CH outpatient clinic. CH consults were further categorized by referral reasons and the type of physician (CH, MH, or fellow) performing the consultations. CH physicians were defined as those whose clinical practice primarily focuses on non-malignant hematologic conditions; one advanced practice provider (APP) was included in this group. Inpatient consults, electronic consults, and return visits were excluded. Results In 2024, a total of 17,153 outpatient consults were completed. Of these, 13.4% were CH, 30.5% were MH and 56.1% were solid tumor oncology. Among CH consults, the most common referral reasons were abnormal blood counts (68.3%), bleeding disorders (10.6%), thrombosis (11.8%), and other hematologic diagnoses (9.3%). Within abnormal blood counts, the leading indications were anemia (50.7%), thrombocytopenia (15.3%), leukopenia (11.0%), leukocytosis (9.1%), and pancytopenia (7.0%). Among bleeding disorders, the top reasons included suspected bleeding diathesis (49.4%), von Willebrand disease (24.5%), Hemophilia A (4.1%), Factor VII deficiency (3.7%), and platelet qualitative defect (3.4%). Thrombosis-related consults were most often for pulmonary embolism or deep vein thrombosis (43.2%), antiphospholipid syndrome (17.7%), thrombophilia (16.2%), portal vein thrombosis (4.1%), and splenic infarct (2.6%). The top ten referrals for a specific hematologic diagnosis were iron deficiency anemia (29.2%), pulmonary embolism or DVT (13.5%), immune thrombocytopenic purpura (10.3%), von Willebrand disease (6.9%), hemoglobinopathy (5.5%), antiphospholipid syndrome (5.5%), thrombophilia (5.1%), anemia of chronic kidney disease (2.4%), aplastic anemia (1.5%), and hereditary spherocytosis (1.4%). Of the 114 physicians at MCCC during the study period, 55 (48.2%) were medical oncologists, 54 (47.4%) primarily practiced MH, and only 5 (4.4%) were dedicated CH physicians. Despite comprising only 4.4% of the hematology/oncology workforce, CH physicians or fellows completed the majority (86.1%) of CH consults; MH physicians completed 13.8%. Conclusion CH consults represent a substantial portion of outpatient hematology referrals at MCCC, primarily for diagnostic evaluation of cytopenias or thrombotic/bleeding symptoms. However, a striking mismatch exists between CH physician representation (4.4%) and CH consult volume (13.4%). This imbalance has implications for quality, timeliness, and continuity of care for patients with non-malignant hematologic conditions. Our findings underscore the urgent need to expand recruitment and career development pathways in CH to address a huge clinical demand.

Abstract Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening hyperinflammatory syndrome resulting from immune dysregulation. While diagnostic and therapeutic guidelines (e.g., HLH-2004) are established for pediatric HLH, adult-onset HLH remains both a diagnostic and therapeutic challenge, with limited characterization and sparse outcome data. Here, we conduct a single-institution retrospective cohort study to evaluate clinical features, causes, and prognostic markers associated with outcomes. Methods: We performed a retrospective chart review of all adult patients (≥18 years) first diagnosed with HLH across all Mayo Clinic sites between January 1, 2006 and July 1, 2025. Diagnosis was based on hematologist adjudication at time of care. Patients with prior diagnoses of HLH or HLH related to T-cell therapy (CAR-T) were excluded. Clinical and laboratory variables were extracted from electronic health records. The primary outcome was overall survival (OS), defined as time from diagnosis of HLH to death or last follow-up. OS was estimated using the Kaplan-Meier method. Multivariable analysis to identify independent predictors of mortality was performed using a Cox proportional hazards regression model, adjusting for age at diagnosis, sex, HLH etiology, and relevant clinical and laboratory parameters. Model discrimination was assessed using Harrell's concordance index (c-index). Descriptive statistics were summarized using median and interquartile range (IQR) for continuous variables and frequency with percentages for categorical variables. Results: A total of 203 patients diagnosed with HLH were included. The median age at diagnosis was 55 years (range 18-86). The cohort was predominantly male (n=130, 64%) and White (n=163, 80%). The majority of diagnoses occurred in more recent years, with 75 patients (36.9%) diagnosed between 2021–2025, 61 (30.0%) between 2016–2020, and 43 (21.2%) between 2011–2015. Prior to HLH diagnosis, 86 patients (42.4%) had a history of malignancy, 55 (27.1%) had a history of autoimmune disease, and 28 (13.8%) had a history of transplant. The most common HLH etiologies were malignancy-associated (n=99, 49%), infectious (n=51, 25%), and autoimmune (n=24, 12%), in addition to idiopathic (n=6, 3%), post-transplant lymphoproliferative disease or graft-vs-host disease (n=3, 1%), drug-induced (n=3, 1%), or primary HLH (n=1, 0.5%). The most common malignancies included T-cell (n=35, 17.2%) and diffuse large B-cell lymphoma (n=24, 11.8%). Forty-four cases (21.7%) were associated with Epstein-Barr virus (EBV), either through overt viremia or malignancies with EBV positivity on pathology report. Five patients (2.5%) had COVID-19–associated HLH and 2 (1.0%) were attributed to immune checkpoint inhibitors. Overall, 164 patients (80.8%) met the HLH-2004 diagnostic threshold of ≥5 out of 8 criteria, while 196 (96.6%) met the HLH-2024 ≥4 of 7 modified criteria. Among patients with available information, elevated ferritin was present in 197 of 198 (99.5%), fever in 185 of 202 (91.6%), cytopenias involving ≥2 lineages in 184 of 199 (92.5%), hemophagocytosis in 156 of 182 (85.7%), elevated sCD25 in 117 of 121 (96.7%), hypertriglyceridemia in 117 of 186 (62.9%), hypofibrinogenemia in 118 of 196 (60.2%), splenomegaly in 125 of 188 (66.5%), and impaired NK cell activity in 16 of 25 (64.0%). In addition, hepatomegaly was noted in 57 of 195 patients (29.2%). After a median follow-up of 58.3 months, median OS was 62 days (95% CI 40-110) from day of diagnosis. In a multivariable Cox proportional hazards model with moderate discrimination (c-index=0.75), after adjusting for age at diagnosis and sex, T-cell lymphoma–driven HLH (HR 1.78, 95% CI 1.05–3.00, p = 0.03) and elevated blood urea nitrogen (median 51.0 mg/dL, IQR 27.9–99.1; HR 2.07, 95% CI 1.37–3.13, p < 0.005) were independently associated with shorter OS Conclusions: In this cohort of adult patients with HLH, malignancy was found to be the most common trigger for HLH. T-cell malignancies in particular were strongly correlated with poor survival. Elevated blood urea nitrogen at diagnosis also identified patients at significantly higher risk of death, consistent with other critical illnesses that can present with multi-organ failure. These findings emphasize the need for adult-specific prognostic tools incorporating disease etiology and organ dysfunction markers to better stratify risk and guide clinical management in adult-onset HLH.

Abstract Background: In 2022, Medicare alone spent $42.1 billion on prescription drugs, with antineoplastic and classical hematology drugs accounting for 44% and 8% of the total, respectively (2024 MedPAC Data Book). While antineoplastic drugs have been extensively studied, classical hematology drugs have received comparatively little attention. We analyzed US Food and Drug Administration (FDA) approvals of classical hematology drugs over the past 30 years and examined their per-patient costs and annual total US sales. Methods: We identified all classical hematology drugs (those prescribed by hematologist/oncologists for non-malignant indications) approved by the FDA from January 1, 1995 to December 31, 2024, including novel pharmaceuticals (synthesized from chemical compounds), biologics (derived from living organisms), and biosimilars (highly similar, but not identical, to biologics previously approved). Cost estimates for 2024 were based on wholesale acquisition costs (WAC), using annual WAC for continuous-duration treatments and typical course WAC for fixed-duration treatments. WAC and US gross sales data for 2024 were obtained from IPD Analytics (Aventura, FL). Results: A total of 98 classical hematology drugs were approved over the past 30 years—11% in 1995–2004, 26% in 2005–2014, and 63% in 2015–2024. These included pharmaceuticals (36%), biologics (54%), and biosimilars (10%). Six gene therapies received approval: 3 for hemophilia and 1 each for sickle disease, beta thalassemia, and sickle cell disease/beta thalassemia (dual indication). Common categories of indications included bleeding (31%), anemia (30%), neutropenia (9%), and thrombocytopenia (9%). Leading diagnoses were hemophilia (25%), chemotherapy-induced neutropenia (9%), thromboembolism (8%), paroxysmal nocturnal hemoglobinuria (PNH; 7%), anemia of chronic kidney disease (6%), iron deficiency anemia (6%), and immune thrombocytopenia (5%). The median cost for gene therapies was $2.9 million per treatment (range: $2.2 million–$3.5 million). Among non-gene therapies, median costs were $3,000 per course for fixed-duration treatments (range: $64–$378,000) and $467,000 annually for continuous-duration treatments (range: $2,400–$1.8 million). The most expensive fixed-duration treatments targeted hemophagocytic lymphohistiocytosis ($378,000/8-week course), while the most expensive continuous-duration treatments were for hemophilia (median: $630,000/year; range: $270,000–$853,000). Estimated 2024 US gross sales across all drugs exceeded $70 billion. Top-selling indications included thromboembolism ($43.5 billion), hemophilia ($6.9 billion), immune thrombocytopenia ($4.9 billion), PNH ($4.7 billion), chemotherapy-induced neutropenia ($2.8 billion), anemia of chronic kidney disease ($2.0 billion), and iron deficiency anemia ($1.8 billion). Total sales for all gene therapies combined were $143 million. Six drugs have been discontinued (year approved/year discontinued/reason): betrixaban (2017/2020/business), daprodustat (2023/2024/business), fidanacogene elaparvovec (2024/2025/business), oprelvekin (1997/2011/business), peginesatide (2012/2013/safety), and voxelotor (2019/2024/safety). There are limitations to our study. Some drugs have non-classical hematology indications (anticoagulants in atrial fibrillation; luspatercept in myelodysplastic neoplasm) and/or may also be prescribed by non-classical hematologists (erythropoiesis stimulating agents by nephrologists and medical oncologists). We were unable to disaggregate the sales data in these situations. Therefore, the annual sales for certain indications may be overestimated. Conclusions: Classical hematology drugs contribute substantially to US prescription drug spending, with over $70 billion in annual sales and medications for thromboembolism accounting for over half of the costs. Approvals have accelerated over the past three decades, doubling each decade. Biologics and biosimilars now represent two-thirds of approvals. Continuous-duration treatments, particularly for rare hereditary diseases like hemophilia, carry significant financial burden, with annual costs per patient often exceeding $0.5 million. In these conditions, if gene therapies demonstrate durable efficacy, they may prove to be cost-effective alternatives. As more gene therapies are developed, evaluating their long-term value relative to chronic high-cost treatments will be essential for shaping future reimbursement and access strategies.

Abstract Immune thrombocytopenia (ITP) carries an increased risk of thrombosis, which may be further amplified by splenectomy and thrombopoietin receptor agonists (TPO-RAs). Although each intervention has been individually studied for its thrombotic risk, data are lacking on the safety of postsplenectomy TPO-RA use. We conducted a retrospective cohort study of adult patients with ITP who underwent splenectomy between 2011 and 2024. Patients were stratified on the basis of postsplenectomy TPO-RA use. The primary outcome was incidence of thrombosis. Secondary outcomes included bleeding, mortality, and hematologic response. Time-to-event analyses and multivariate Cox regression were performed. Among 88 patients, 37 (42%) patients received TPO-RAs after splenectomy. Thrombosis occurred in 17 patients in the TPO-RA group vs 14 patients in the non–TPO-RA group (P = .07). The 10-year cumulative incidence of thrombosis was numerically higher in the TPO-RA group (57% vs 36%), with clustering of events within the 3 months of postsplenectomy TPO-RA initiation. Venous events predominated; arterial events were rare. No significant differences were observed in bleeding or mortality rates between groups. Platelet counts alone did not independently affect bleeding or thrombosis. TPO-RA use after splenectomy was not significantly associated with increased thrombosis risk. However, early initiation may coincide with a high-risk period, and the sustained numerical difference in cumulative incidence throughout follow-up highlights potential clinical relevance. These findings support the need for individualized thromboprophylaxis and prospective evaluation of TPO-RA safety in this setting.