Research and Practice in Thrombosis and Haemostasis最新文献

{"title":"Gene therapy in hemophilia: the dawn of a new era","authors":"Roberta Gualtierotti ,&nbsp;Andrea Giachi ,&nbsp;Niccolò Bitto ,&nbsp;Vincenzo La Mura ,&nbsp;Flora Peyvandi","doi":"10.1016/j.rpth.2024.102640","DOIUrl":"10.1016/j.rpth.2024.102640","url":null,"abstract":"<div><div>Hemophilia A and B are hereditary bleeding disorders associated with the X chromosome, stemming from genetic defects in the coding of coagulation factor (F)VIII or FIX protein, leading to partial or complete deficiency. In the absence of effective prophylaxis, these deficiencies can result in irreversible joint damage, known as hemophilic arthropathy, and subsequent disability.</div><div>Despite advancements in hemophilia treatment, individuals with severe forms of the disease continue to face a high risk of bleeding, particularly in instances of trauma or major surgical procedures. In such scenarios, it remains imperative to administer replacement or bypassing drugs, especially when inhibitors are present.</div><div>Within this context, gene therapy emerges as a compelling alternative, ensuring sustained expression of the deficient factor at levels often surpassing current recommendations. Some studies report an effect lasting up to 8 years, contributing significantly to clinical improvement and enhancing the quality of life for patients. However, a comprehensive evaluation of this innovative therapy is essential, encompassing both its benefits and potential risks. It is crucial to undertake a multidisciplinary assessment, engage in thoughtful discussions with the patient, and closely monitor the therapy’s effects and any eventual side effects of therapy. This approach aims to facilitate an informed and collaborative decision-making process, ultimately maximizing the benefits for each individual patient.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102640"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of bleeding in thrombotic thrombocytopenic purpura in the precaplacizumab era: a retrospective nationwide analysis","authors":"Amir A. Mahmoud ,&nbsp;Mariam Mostafa ,&nbsp;Ali Abdelhay ,&nbsp;Mouhamed Yazan Abou-Ismail ,&nbsp;Shruti Chaturvedi","doi":"10.1016/j.rpth.2024.102654","DOIUrl":"10.1016/j.rpth.2024.102654","url":null,"abstract":"<div><h3>Background</h3><div>The addition of caplacizumab to immune thrombotic thrombocytopenia (iTTP) treatment options has led to a renewed interest in characterizing the epidemiology and risk factors for bleeding in iTTP. Limited data exist on the bleeding risk in iTTP due to systemic underreporting in earlier cohorts.</div></div><div><h3>Objectives</h3><div>To describe the incidence, patterns, and predictors of bleeding in hospitalized iTTP patients independent of caplacizumab use.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed the National Inpatient Sample database (2012-2019) and identified adult patients with a diagnosis of iTTP. Predictors of bleeding were determined by multivariable logistic regression analysis.</div></div><div><h3>Results</h3><div>We identified 3103 iTTP hospitalizations; bleeding occurred in 594 (19.1%), and 157 (5.1%) were characterized by major bleeding. Mucocutaneous bleeding (7.6%) was the most frequent type of bleeding and included heavy menstrual bleeding (2.6%), gingival (2.3%), epistaxis (1.4%), and skin/procedure-related bleeding (1.3%). This was followed closely by gastrointestinal bleeding (5.6%). Patients with bleeding were more likely to be Hispanic, have a weekend admission, and have a higher prevalence of comorbidities. In the multivariable analysis, Hispanic race (odds ratio [OR], 1.48; 1.14-1.91), Asian/Pacific Islander/Native American race (OR, 2.04; 1.51-2.76), coronary artery disease (OR, 1.70; 1.38-2.11), heart failure (OR, 1.39; 1.13-1.72), autoimmune disease (OR, 2.61; 2.08-3.26), Charlson Comorbidity Index ≥ 3 (OR, 2.08; 1.66-2.61), weekend admission (OR, 1.45; 1.22-1.72), and delay ≥2 days in plasma exchange initiation (OR, 1.63; 1.38-1.92), were significantly associated with major bleeding.</div></div><div><h3>Conclusions</h3><div>Bleeding is a relatively common issue in acute iTTP that has not been adequately addressed in existing literature. Further studies are needed to elucidate this risk and associated factors, especially given the incorporation of caplacizumab in the treatment of iTTP.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102654"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"External validation of a novel cancer-associated venous thromboembolism risk assessment score in a safety-net hospital","authors":"Karlynn N. Dulberger ,&nbsp;Jennifer La ,&nbsp;Ang Li ,&nbsp;Saran Lotfollahzadeh ,&nbsp;Asha Jose ,&nbsp;Nhan V. Do ,&nbsp;Mary T. Brophy ,&nbsp;J. Michael Gaziano ,&nbsp;Katya Ravid ,&nbsp;Vipul C. Chitalia ,&nbsp;Nathanael R. Fillmore","doi":"10.1016/j.rpth.2024.102650","DOIUrl":"10.1016/j.rpth.2024.102650","url":null,"abstract":"<div><h3>Background</h3><div>Cancer-associated thrombosis (CAT) is a leading cause of death in patients diagnosed with cancer. However, pharmacologic thromboprophylaxis use in cancer patients must be carefully evaluated due to a 2-fold increased risk of experiencing a major bleeding event within this population. The electronic health record CAT (EHR-CAT) risk assessment model (RAM) was recently developed, and reports improved performance over the widely used Khorana score. Extensive RAM external validation is crucial to determine accuracy across diverse patient populations prior to clinical utilization.</div></div><div><h3>Objectives</h3><div>To externally validate EHR-CAT using data from 2103 patients with cancer at the Boston Medical Center (BMC), New England’s largest safety-net hospital, and to compare this RAM with the Khorana score.</div></div><div><h3>Methods</h3><div>We conducted a retrospective study of BMC cancer patients diagnosed between January 2014 and December 2022 using data from the BMC tumor registry and EHR system. We validated the RAM using measures of discrimination and calibration.</div></div><div><h3>Results</h3><div>The EHR-CAT score exhibited a strong ability to discriminate the risk of CAT (C statistic, 0.67), which was substantially higher than the classic Khorana score (C statistic, 0.58). This increased discrimination power reflects the 20% of patients that were reclassified into high or low risk by the expanded score. Model calibration was also strong in this dataset.</div></div><div><h3>Conclusion</h3><div>In our external validation, the recently published EHR-CAT score showed clear and improved separation of patients at high and low risk for CAT. The utilization of this expanded CAT score could facilitate improved targeting of at-risk cancer patients for prophylactic therapy.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102650"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type of D-dimer assay determines the diagnostic yield of computed tomography in patients suspected for pulmonary embolism","authors":"Jorn L.J.C. Assmann ,&nbsp;Adriaan J. van Gammeren ,&nbsp;Reinier A. Sprenger ,&nbsp;Saskia de Wit ,&nbsp;Huib Ceelie ,&nbsp;Frank W.G. Leebeek ,&nbsp;Mark W.M. Schellings","doi":"10.1016/j.rpth.2024.102638","DOIUrl":"10.1016/j.rpth.2024.102638","url":null,"abstract":"<div><h3>Background</h3><div>Pulmonary embolism (PE) is a life-threatening condition with high morbidity and mortality. The diagnosis of PE is challenging due to nonspecific symptoms, making reliable diagnostic tools essential. This study addresses the clinical impact of interassay variability in D-dimer measurements on the utilization and diagnostic yield of computed tomography pulmonary angiography (CTPA).</div></div><div><h3>Objectives</h3><div>To investigate the effect of different D-dimer assays on the decision to perform CTPA and the subsequent diagnostic yield in patients with suspected PE.</div></div><div><h3>Methods</h3><div>This retrospective, multicenter cohort study analyzed data from 3 teaching hospitals in the southwest region of the Netherlands, covering the years 2018, 2019, 2022, and 2023. The study included data from 40,096 clinically requested D-dimer results and 11,372 CTPA records of patients with suspected PE. The D-dimer assays used were the Roche Tina-quant and Siemens INNOVANCE.</div></div><div><h3>Results</h3><div>The study found significant differences in CTPA utilization and diagnostic yield based on the D-dimer assay used. In 2018 to 2019, hospitals using the Roche Tina-quant assay ordered 21% fewer CTPA scans and had a 9% higher positivity rate compared with those using the Siemens INNOVANCE assay.</div></div><div><h3>Conclusion</h3><div>The findings highlight the necessity for assay-specific cutoff values or, ideally, the standardization of the D-dimer assay to optimize the accuracy and efficiency of PE diagnosis. This study demonstrates that the choice of D-dimer assay significantly influences the clinical management of suspected PE, affecting both the number of CTPA scans performed and the positivity rate of these scans. Implementing assay-specific cutoff values or standardization of the D-dimer assay could reduce unnecessary CTPA scans, minimize patient exposure to radiation, and lower healthcare costs. These results advocate enhanced collaboration between clinicians and laboratory specialists to accurately interpret D-dimer results within the context of the specific assay used. Future research should validate these findings in prospective studies and explore standardized protocols that account for interassay variability.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102638"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silencing of the von Willebrand factor gene in proatherothrombotic APOE∗3-Leiden.CETP transgenic mice","authors":"Yvonne K. Jongejan ,&nbsp;Richard J. Dirven ,&nbsp;Elisa Schrader Echeverri ,&nbsp;Anke J.L. de Jong ,&nbsp;Amanda C.M. Pronk ,&nbsp;Sander Kooijman ,&nbsp;Patrick C.N. Rensen ,&nbsp;James E. Dahlman ,&nbsp;Jeroen C.J. Eikenboom ,&nbsp;Bart J.M. van Vlijmen","doi":"10.1016/j.rpth.2025.102699","DOIUrl":"10.1016/j.rpth.2025.102699","url":null,"abstract":"<div><h3>Background</h3><div>Elevated von Willebrand factor (VWF) levels correlate with higher risk of atherosclerosis-related arterial thrombosis (atherothrombosis). Silencing the <em>VWF</em> gene via small-interfering RNAs (siRNAs) could mitigate this risk. Previous studies successfully delivered siRNA to the endothelium of healthy, wild-type (WT) mice using lipid nanoparticles (LNPs).</div></div><div><h3>Objectives</h3><div>This study aimed to investigate whether the LNP-siRNA strategy could achieve endothelium-specific <em>Vwf</em>-silencing under diseased conditions of prolonged hypercholesterolemia and atherothrombosis-prone vasculature.</div></div><div><h3>Methods</h3><div>Female transgenic mice expressing a variant of human <em>APOE∗3</em> (ie, <em>APOE∗3-Leiden</em>) and human cholesteryl ester transfer protein (<em>CETP</em>), fed a cholesterol-enriched diet for 18 weeks, received an intravenous injection of LNP-encapsulated siRNA targeting <em>Vwf</em> (si<em>Vwf</em>) or scrambled control siRNA at 1.5 mg siRNA/kg. For comparison, the same LNP-siRNAs were administered to young, chow-fed WT mice. Plasma VWF and <em>Vwf</em> mRNA levels were measured 96 hours after injection, with immunofluorescence analysis of lungs and heart aortic root to assess VWF protein expression.</div></div><div><h3>Results</h3><div><em>APOE∗3-Leiden.CETP</em> mice exhibited elevated plasma VWF levels compared with WT mice, alongside hypercholesterolemia and aortic atherosclerosis. si<em>Vwf</em> administration led to over 85% reduction in plasma VWF in both strains, with a strong reduction in lung <em>Vwf</em> mRNA and VWF protein in the pulmonary endothelium. Similarly, si<em>Vwf</em> treatment resulted in the virtual absence of VWF protein in the endothelial lining of the aortic root of both nondiseased (WT mice) and atherosclerotic (<em>APOE∗3-Leiden.CETP</em> mice) vessel walls.</div></div><div><h3>Conclusion</h3><div>The LNP-siRNA targeting <em>Vwf</em> strongly reduced plasma and endothelial VWF in mice with hypercholesterolemia and advanced atherosclerosis, indicating feasibility to target endothelial VWF under proatherothrombotic conditions.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102699"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recombinant factor VIIa: new insights into the mechanism of action through product innovation","authors":"Miguel A. Escobar ,&nbsp;Maureane Hoffman ,&nbsp;Giancarlo Castaman ,&nbsp;Cedric Hermans ,&nbsp;Johnny Mahlangu ,&nbsp;Johannes Oldenburg ,&nbsp;Charles L. Percy ,&nbsp;Mark T. Reding ,&nbsp;Amy D. Shapiro ,&nbsp;Steven W. Pipe","doi":"10.1016/j.rpth.2024.102670","DOIUrl":"10.1016/j.rpth.2024.102670","url":null,"abstract":"<div><div>Management of bleeding in persons with hemophilia and inhibitors involves treatment with bypassing agents, including recombinant activated factor VII (rFVIIa). Two rFVIIa products are commercially approved for use in the United States and the European Union. Eptacog alfa and eptacog beta share the same amino acid sequence but differ in posttranslational modifications. Although rFVIIa has been used to manage bleeding in persons with hemophilia and inhibitors for over 30 years, its mechanisms of action is still being studied. <em>In vitro</em> and <em>in vivo</em> studies have suggested that rFVIIa could promote hemostasis by (1) increasing tissue factor-dependent activation of factor (F)X (FX); (2) directly activating FX on the surface of activated platelets; and (3) downregulating protein C anticoagulant activity through binding to the endothelial protein C receptor (EPCR). Studies of rFVIIa and rFVIIa variants in murine models demonstrate that platelet-dependent activity is sufficient for hemostatic efficacy. Dosing levels required in clinical practice are most consistent with a platelet-dependent mechanism of action. However, <em>in vivo</em> models also suggest that pathways involving EPCR binding contribute to rFVIIa hemostatic activity. Eptacog beta displays increased platelet- and EPCR-dependent endothelial cell binding compared to eptacog alfa. Thus, the relative contribution of these mechanisms to the overall hemostatic efficacy of eptacog alfa and eptacog beta may differ. Further research is required to assess the clinical relevance of these differences. A better understanding of the mechanisms by which rFVIIa promotes hemostasis in patients will provide insights when evaluating clinical outcomes of safety and efficacy for innovative bypassing therapies.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102670"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143155135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contemporary approaches to treat people with hemophilia: what’s new and what’s not?","authors":"Leonard A. Valentino ,&nbsp;Maria E. Santaella ,&nbsp;Samantha A. Carlson ,&nbsp;Michael Recht","doi":"10.1016/j.rpth.2025.102696","DOIUrl":"10.1016/j.rpth.2025.102696","url":null,"abstract":"<div><div>The care of people with hemophilia with access to treatment has evolved over the past 70 years, with an average life expectancy like unaffected peers. For people with hemophilia living in low- and middle-income countries, the same is not true because of the lack of access to diagnosis and treatment. It is imperative to close gaps in care that exist throughout the world.</div><div>Here, we provide a narrative review of hemophilia and the treatments available to people with hemophilia A and B with the goal of achieving a hemophilia-free state. We aim to provide information on what is new and what gaps remain that preclude equitable outcomes for everyone with hemophilia.</div><div>Information on the current state of hemophilia care and outcomes, the products available for the treatment of people with hemophilia, comprehensive interdisciplinary care of people with hemophilia, and the remaining gaps in care for people with hemophilia were assembled by the authors using relevant literature.</div><div>Research must focus on preventing all bleeding, and new approaches to detect joint bleeding are needed. Training on and implementation of comprehensive interdisciplinary care is needed to elevate the standards of care in low- and middle-income countries. The development and introduction of improved factor replacement and nonfactor products, such as second-generation bispecific monoclonal antibodies and targeted inhibitors of the anticoagulant mechanisms along with genetic therapies, have the possibility of normalizing hemostasis and achieving health equity for people with hemophilia.</div><div>Improved outcomes and, ultimately, health equity, can only be realized if diagnosis, education, and care are accessible to everyone living with hemophilia worldwide.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102696"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The risk for psychiatric disorders in offspring from thrombosis-prone pedigrees in Sweden: a nationwide family study","authors":"Bengt Zöller,&nbsp;Jan Sundquist,&nbsp;Kristina Sundquist,&nbsp;Henrik Ohlsson","doi":"10.1016/j.rpth.2025.102692","DOIUrl":"10.1016/j.rpth.2025.102692","url":null,"abstract":"<div><h3>Background</h3><div>Psychiatric disorders have been associated with venous thromboembolism (VTE). However, to our knowledge, no nationwide study has examined the familial association between VTE and psychiatric disorders.</div></div><div><h3>Objectives</h3><div>We took a pedigree-based approach and examined the risk of psychiatric disorders in offspring from extended pedigrees according to the densities of VTE in pedigrees.</div></div><div><h3>Methods</h3><div>This was a Swedish national family study. We identified a total of 482,184 Swedish pedigrees from the Swedish Multigeneration Register containing a mean of 14.2 parents, aunts/uncles, grandparents, and cousins of a core full-sibship that we termed the pedigree offspring (<em>n</em> = 751,060). We then derived 8 empirical classes of these pedigrees based on the density of cases of VTE. The risk was determined in offspring for psychiatric disorders as a function of VTE density in their pedigrees. Diagnoses of VTE and psychiatric disorders (F00-F69) were determined according to the International Classification of Diseases codes in Swedish registers. All results were Bonferroni corrected.</div></div><div><h3>Results</h3><div>Higher VTE density, especially for females in pedigrees, was significantly but weakly associated in the offspring with a higher risk of psychiatric disorders. Moreover, VTE density in pedigrees was significantly associated in the offspring with substance abuse disorders, mood (affective) disorders, neurotic, stress-related, and somatoform disorders, behavioral syndromes associated with psychological disturbances and physical factors, personality disorders of adult personality and behavior, depression, and anxiety disorders.</div></div><div><h3>Conclusion</h3><div>Offspring of pedigrees with a high density of VTE, especially for females, are slightly disadvantaged regarding several psychiatric disorders. VTE shares familial susceptibility, albeit weak, with several psychiatric disorders.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102692"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A literature review of major surgery experience with emicizumab in people with hemophilia A without factor VIII inhibitors","authors":"Giancarlo Castaman ,&nbsp;Stacy E. Croteau ,&nbsp;Doris Quon ,&nbsp;Lucy Lee ,&nbsp;Letizia Polito ,&nbsp;Víctor Jiménez-Yuste","doi":"10.1016/j.rpth.2025.102693","DOIUrl":"10.1016/j.rpth.2025.102693","url":null,"abstract":"<div><div>People with hemophilia A have a total or partial deficiency of factor (F)VIII, causing spontaneous and/or traumatic bleeding into the joints, muscles, and soft tissues. Major surgery may be required to restore joint mobility or treat the symptoms of common comorbidities in people with hemophilia A. Additional factor replacement is recommended during the perioperative period; collated information on the experience of emicizumab-treated people with hemophilia A during major surgery is currently lacking. To provide a consolidated narrative summary of the experience with emicizumab in people with hemophilia A without FVIII inhibitors undergoing major surgery, a comprehensive literature search was performed using PubMed/MEDLINE (cut-off date: March 31, 2024); the abstract books for applicable congresses (2016–2024) were searched manually. Studies were included if reporting original data on people with hemophilia A of all ages and hemophilia A severities without FVIII inhibitors on emicizumab prophylaxis who had undergone major surgery. Outcomes collected included perioperative surgical management, adverse events, and bleeding events. Twenty publications were included; 72 procedures were reported. Twenty-two orthopedic and 34 other major procedures were specifically described. FVIII replacement was used to manage 66 procedures perioperatively, and 25 procedures were managed in conjunction with antifibrinolytics. Fifteen procedures resulted in a bleeding event, and one individual experienced a thrombotic event. No deaths were reported. This review provides a consolidated narrative of the currently reported experiences of emicizumab-treated people with hemophilia A without FVIII inhibitors undergoing major surgery, helping to support the future management decisions of emicizumab-treated people with hemophilia A during surgery.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102693"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adeno-associated virus-based gene therapy for hemophilia–addressing the gaps","authors":"Wolfgang Miesbach ,&nbsp;Paul Batty ,&nbsp;Pratima Chowdary ,&nbsp;Sylvia Fong ,&nbsp;Radoslaw Kaczmarek ,&nbsp;Frank W.G. Leebeek ,&nbsp;Brian Long ,&nbsp;Johnny Mahlangu ,&nbsp;Mike Makris ,&nbsp;Glenn F. Pierce ,&nbsp;Steven W. Pipe ,&nbsp;Alok Srivastava ,&nbsp;Jan Voorberg ,&nbsp;Flora Peyvandi","doi":"10.1016/j.rpth.2024.102673","DOIUrl":"10.1016/j.rpth.2024.102673","url":null,"abstract":"<div><div>Adeno-associated virus-based gene therapy for hemophilia has emerged as a revolutionary treatment option, offering potential correction of clotting factor deficiency through a single intravenous infusion of functional genes directed to hepatocytes. With 3 gene therapies recently approved, this approach shows promise in transforming the lives of individuals with hemophilia. However, the complexity of gene therapy and the lack of standardization of methods in different components of this therapy can lead to unique challenges for clinical implementation. This manuscript follows literature reviews and structured discussions by the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee Working Group on Gene Therapy that identified specific areas requiring standardization of methods, including viral vector production, liver function assessment, quantification of factor (F)VIII and FIX expression levels, assessment of antiadeno-associated viral antibodies, and genomic integration detection methods. Standardization strategies aim to achieve consistent vector quality, effective patient selection, and uniform assessment methods by implementing advanced laboratory techniques and standardized protocols. Standardizing these parameters is essential for improving the understanding of short-term and long-term safety and efficacy of gene therapy in hemophilia. This effort aims to enhance the predictability of individual responses, address variability in outcomes, and ultimately provide more effective, safer, and personalized treatment options for individuals with hemophilia.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102673"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}