Research and Practice in Thrombosis and Haemostasis最新文献

{"title":"Comparing rates of clinically relevant epistaxis in patients taking warfarin versus direct oral anticoagulants","authors":"Khristian S. Burke , Xiaowen Kong , Brian Haymart , Debbie DeCamillo , Mona Ali , Geoff Barnes , Scott Kaatz","doi":"10.1016/j.rpth.2024.102630","DOIUrl":"10.1016/j.rpth.2024.102630","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102630"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932579","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":"Impact of self-reported race on Villalta Scale postthrombotic syndrome scores and correlation with venous disease-specific quality of life: an exploratory analysis of the Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis Trial","authors":"James Shih MD ,&nbsp;Chu-Shu Gu PhD ,&nbsp;Suresh Vedantham MD ,&nbsp;John Kaufman MD ,&nbsp;Susan R. Kahn MD","doi":"10.1016/j.rpth.2024.102609","DOIUrl":"10.1016/j.rpth.2024.102609","url":null,"abstract":"<div><h3>Background</h3><div>The Villalta Scale (VS) to diagnose postthrombotic syndrome (PTS) consists of 5 patient-reported leg symptoms and 6 clinician-rated leg signs. It is unknown how the scale performs across racial groups.</div></div><div><h3>Objectives</h3><div>Our study explored if there were differences in VS scores, particularly clinician-rated signs components, according to self-reported race.</div></div><div><h3>Methods</h3><div>Exploratory analysis of the ATTRACT trial, a randomized controlled trial conducted at 56 US sites that investigated pharmacomechanical catheter-directed thrombolysis to prevent PTS after proximal deep vein thrombosis (DVT). At the 6-month visit after randomization, we compared self-reported Black (n = 123) and White (n = 541) participants for mean total VS score, VS symptoms score, VS signs score, individual signs scores, and correlation coefficients between VS signs and VS symptoms scores and between VS signs and Venous Insufficiency Epidemiological and Economic Study Quality of Life (VEINES-QOL) scores (a self-reported venous disease-specific quality of life measure).</div></div><div><h3>Results</h3><div>Mean total VS score (4.67 vs. 4.12, <em>P</em> = .54),VS signs score (1.66 vs. 2.00, <em>P</em> = .07), and VS symptoms score (2.83 vs. 2.04, <em>P</em> = .10) were similar between Black and White participants. The mean score for one individual VS sign, venous ectasia, was lower in Black vs. White participants (0.24 vs. 0.63, <em>P</em>&lt; .01). There was similar, modest correlation in Black and White participants between VS signs and VS symptoms scores (<em>r</em>_black = 0.19; <em>r</em>_white = 0.23) and between VS signs and VEINES-QOL scores (<em>r</em>_black = −0.32; <em>r</em>_white = −0.30). Results were adjusted for ATTRACT trial treatment group, age, sex, body mass index, DVT extent, hypertension, diabetes, dyslipidemia, and congestive heart failure.</div></div><div><h3>Conclusion</h3><div>The findings suggest that some differences in VS scores exist according to self-reported race. It is unclear whether these reflect clinicians’ underrating of some VS signs and/or differences in PTS severity. Further work is needed to understand how the VS performs across racial groups.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102609"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702286","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":"Inhibitor development upon switching from plasma-derived to recombinant factor VIII in previously untreated patients with severe hemophilia A: the PUP-SWITCH study","authors":"Syna Miri ,&nbsp;Frits R. Rosendaal ,&nbsp;Kaan Kavakli ,&nbsp;Peyman Eshghi ,&nbsp;Soha Mohammadi Moghaddam ,&nbsp;Sara Scardo ,&nbsp;Behnaz Habibpanah ,&nbsp;Mohsen Elalfy ,&nbsp;Susan Halimeh ,&nbsp;Gabriella Nicolò ,&nbsp;Dilek Gökçebay ,&nbsp;Namık Özbek ,&nbsp;Tiraje Celkan ,&nbsp;Ahmad Mohammadi ,&nbsp;Mehran Karimi ,&nbsp;Amin Shahsavani ,&nbsp;Bariş Yılmaz ,&nbsp;Canan Albayrak ,&nbsp;Burcak Gunes ,&nbsp;Zühre Kaya ,&nbsp;Flora Peyvandi","doi":"10.1016/j.rpth.2024.102595","DOIUrl":"10.1016/j.rpth.2024.102595","url":null,"abstract":"<div><h3>Background</h3><div>The SIPPET randomized clinical trial showed that in previously untreated patients (PUPs) with severe hemophilia A, treatment with plasma-derived factor (F)VIII (pdFVIII) within the first 50 exposure days (EDs) was associated with a lower cumulative incidence of inhibitors than with recombinant FVIII (rFVIII). Switching to rFVIII beyond 50 EDs with pdFVIII is a treatment often implemented by many centers. The question is whether or not this switch may induce a risk of inhibitor development.</div></div><div><h3>Objectives</h3><div>We investigated if in PUPs with severe hemophilia A switched after 50 EDs from pdFVIII to rFVIII, a novel inhibitor peak appears.</div></div><div><h3>Methods</h3><div>The PUP-SWITCH observational retrospective study was designed to investigate the cumulative incidence of novel inhibitors after switching PUPs to rFVIII after 50 and before 150 EDs. Hemophilia centers that routinely switched PUPs from pdFVIII to rFVIII within this exposure time frame were invited to participate. Patients were followed up for at least 50 EDs after the switch.</div></div><div><h3>Results</h3><div>Ninety-seven patients were evaluated, and 87 were included according to eligibility criteria between 2020 and 2022. Only one of them developed an inhibitor 20 EDs after switching, so the cumulative incidence was 1.15% (95% CI, 0.03%-6.24%).</div></div><div><h3>Conclusion</h3><div>PUP-SWITCH, a study focusing on PUPs undergoing a product class switch from pdFVIII to rFVIII after 50 EDs, showed that switching appears to be safe pertaining to the risk of development of new inhibitors.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102595"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702288","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":"Stability of the thromboxane B2 biomarker of low-dose aspirin pharmacodynamics in human whole blood and in long-term stored serum samples","authors":"Giovanna Petrucci ,&nbsp;Alessandro Rizzi ,&nbsp;Simone Bellavia ,&nbsp;Francesco Dentali ,&nbsp;Giovanni Frisullo ,&nbsp;Dario Pitocco ,&nbsp;Paola Ranalli ,&nbsp;Pier Andrea Rizzo ,&nbsp;Irene Scala ,&nbsp;Mauro Silingardi ,&nbsp;Elisa Zagarrì ,&nbsp;Gualberto Gussoni ,&nbsp;Bianca Rocca","doi":"10.1016/j.rpth.2024.102623","DOIUrl":"10.1016/j.rpth.2024.102623","url":null,"abstract":"<div><h3>Background</h3><div>Serum thromboxane B₂ (sTXB₂) is a validated biomarker of low-dose aspirin pharmacodynamics. In the original method, nonanticoagulated blood samples must be incubated at 37 °C immediately after withdrawal, centrifuged and serum supernatant should be frozen until assayed. Timely completion of all preanalytical steps may affect the feasibility and quality of sTXB₂ measurements. The storage duration of frozen serum can also affect sTXB₂ stability.</div></div><div><h3>Objectives</h3><div>We assessed the stability of sTXB₂ in clotted blood samples stored at 4 °C before further processing and in sera stored at −40 °C for over a decade.</div></div><div><h3>Methods</h3><div>Venous whole blood withdrawn from individuals on chronic low-dose aspirin was dispensed in different tubes and immediately incubated at 37 °C for 1 hour. The reference tube was promptly processed following the original protocol; the remaining tubes were stored at 4 °C for 12 to 72 hours before further processing. Sera stored at a controlled −40 °C temperature for &lt;1 to 15 years were reassayed. Values within the interassay variation limits (±9%) vs baseline were considered acceptable.</div></div><div><h3>Results</h3><div>Baseline sTXB₂ values (median, 5.4 ng/mL; IQR, 2.4-13.4 ng/mL; <em>n</em> = 40) were comparable with those in samples at 4 °C up to 48 hours (median, 97% [IQR, 86%-104%] of the reference; <em>n</em> = 26), but at 72 hours, the variability exceeded the interassay variation. Thromboxane B₂ levels were stable in frozen sera for up to 10 years (median, 101% [IQR, 87%-108%] of the reference; <em>n</em> = 32) but decreased significantly afterward (median, 87% [IQR, 74%-109%] at 15 years; <em>P</em> = .005; <em>n</em> = 32).</div></div><div><h3>Conclusion</h3><div>Thromboxane B₂ is stable in clotted blood samples stored at 4 °C for up to 48 hours before further processing and in serum samples stored at −40 °C over 10 years.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102623"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759317","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":"Primary thromboprophylaxis in ambulatory symptomatic patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials","authors":"Davide Di Vece ,&nbsp;Marco Valgimigli ,&nbsp;Elliot Barnathan ,&nbsp;Jean M. Connors ,&nbsp;Frank Cools ,&nbsp;Ulrike Held ,&nbsp;Ajay K. Kakkar ,&nbsp;Gregory Piazza ,&nbsp;David Spirk ,&nbsp;Saverio Virdone ,&nbsp;Nils Kucher ,&nbsp;Stefano Barco","doi":"10.1016/j.rpth.2024.102613","DOIUrl":"10.1016/j.rpth.2024.102613","url":null,"abstract":"<div><h3>Background</h3><div>The global impact of the COVID-19 pandemic has prompted the search for strategies to improve outcomes in affected individuals, including those initially managed in outpatient settings. Thromboembolic events have been reported as a concerning complication.</div></div><div><h3>Objectives</h3><div>The aim of this study was to evaluate efficacy and safety of primary thromboprophylaxis in outpatients with COVID-19. The study protocol was registered in PROSPERO (CRD42022362776).</div></div><div><h3>Methods</h3><div>The study adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and conducted a comprehensive search of PubMed/MEDLINE, <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, and OVID/Embase and CENTRAL from Cochrane for studies up to December 11, 2023, without language restrictions. Randomized controlled trials comparing prophylactic-dose anticoagulation with placebo or standard of care in symptomatic outpatients with COVID-19 were included in this analysis. The primary outcome was the composite of all-cause hospitalization and death within 30 days. Secondary outcomes included venous thromboembolism, the composite of venous thromboembolism and major arterial cardiovascular events, and the individual components of the primary outcome.</div></div><div><h3>Results</h3><div>Seven randomized controlled trials and 3758 COVID-19 outpatients were included. When compared with placebo or standard of care, thromboprophylaxis was associated with similar rates of all-cause hospitalization or mortality (relative risk, 1.00; 95% CI, 0.77-1.31) and lower rates of venous thromboembolism (relative risk, 0.28; 95% CI, 0.08-0.94), corresponding to a 0.6% absolute risk reduction and number needed to treat of 174.</div></div><div><h3>Conclusion</h3><div>Thromboprophylaxis in symptomatic COVID-19 outpatients led to reduction in venous thromboembolism risk, with no impact on hospitalization or death. However, the overall low absolute risk reduction may not support its routine use.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102613"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759318","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":"Outcomes of patients with acute pulmonary embolism managed in-house vs those transferred between hospitals: a retrospective observational study","authors":"Priyanka Sridhar ,&nbsp;Hong Yu Wang ,&nbsp;Agostina Velo ,&nbsp;Destiny Nguyen ,&nbsp;Avinash Singh ,&nbsp;Abdul Rehman ,&nbsp;Jason Filopei ,&nbsp;Madeline Ehrlich ,&nbsp;Robert Lookstein ,&nbsp;David J. Steiger","doi":"10.1016/j.rpth.2024.102606","DOIUrl":"10.1016/j.rpth.2024.102606","url":null,"abstract":"<div><h3>Background</h3><div>Interhospital transfer (IHT) for acute pulmonary embolism (PE) is increasingly performed to improve access to advanced reperfusion therapies. It is unclear if outcomes of patients undergoing IHT are comparable with those of patients presenting in-house to hospitals with PE Response Team (PERT) capabilities.</div></div><div><h3>Objectives</h3><div>To determine whether outcomes of patients with acute PE undergoing IHT differ from those of patients presenting in-house.</div></div><div><h3>Methods</h3><div>We retrospectively reviewed 386 patients with acute PE who were treated by PERT at 1 of 3 urban teaching hospitals in the Mount Sinai Health System in New York City from January 2021 to October 2023. Propensity score–weighted analysis was performed to compare the outcomes of patients managed in-house with those of patients undergoing IHT.</div></div><div><h3>Results</h3><div>Two hundred eighty-four patients presented in-house, while 102 were transferred from other hospitals. Median PE Severity Index score was 84, and 3 (0.8%), 80 (20.7%), 237 (61.4%), and 66 (17.1%) had low-risk, intermediate low–risk, intermediate high–risk, and high-risk PE. Odds of receiving systemic thrombolysis (odds ratio [OR], 1.06; <em>P</em> = .06) or advanced therapies (OR, 0.95; <em>P</em> = .003) were not significantly different between the 2 groups. Rates of 30-day mortality, major bleeding, and readmission were 6.9%, 2.9%, and 9.8% for the IHT group and 10.6%, 2.1%, and 13% for the in-house group, respectively. IHT patients had lower odds of 30-day mortality (OR, 0.88; <em>P</em> = .003) and higher odds of major bleeding (OR, 1.03; <em>P</em> = .04).</div></div><div><h3>Conclusion</h3><div>PERT-guided IHT for patients with acute PE was associated with reduced mortality but increased risk of bleeding compared with patients managed in-house at hospitals with PERT capabilities.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102606"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748723","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":"Nonneutralizing antibodies in Nordic persons with moderate hemophilia A and B (the MoHem study)","authors":"Ragnhild J. Måseide MD, PhD ,&nbsp;Erik Berntorp MD, PhD ,&nbsp;Jan Astermark MD, PhD ,&nbsp;Anna Olsson MD, PhD ,&nbsp;Maria Bruzelius MD, PhD ,&nbsp;Tony Frisk MD, PhD ,&nbsp;Vuokko Nummi MD, PhD ,&nbsp;Riitta Lassila MD, PhD ,&nbsp;Karin Strandberg MD, PhD ,&nbsp;Geir E. Tjønnfjord MD, PhD ,&nbsp;Pål A. Holme MD, PhD","doi":"10.1016/j.rpth.2024.102611","DOIUrl":"10.1016/j.rpth.2024.102611","url":null,"abstract":"<div><h3>Background</h3><div>The impact of nonneutralizing antibodies (NNAs) in moderate hemophilia is elusive.</div></div><div><h3>Objectives</h3><div>To explore the presence of NNAs in Nordic persons with moderate hemophilia A (MHA) and B (MHB) in relation to treatment modality, clinical outcome, history of inhibitor, and the corresponding factor VIII (FVIII)/factor IX (FIX) gene mutation.</div></div><div><h3>Methods</h3><div>A cross-sectional multicenter study covering persons with MHA and MHB in Sweden, Finland, and Norway. Inhibitors were analyzed with the Bethesda assay, and NNAs were detected by enzyme-linked immunosorbent assay.</div></div><div><h3>Results</h3><div>Plasma samples from 137 MoHem study participants (median age 29 years; Q1-Q3, 15-54) were analyzed. NNAs were present in 11 of 82 (13%) of people with MHA and 7 of 55 (13%) of those with MHB irrespective of prophylactic or on-demand treatment, most frequently after 150 exposure days (EDs). Three NNA positive patients had a history of high-titer inhibitor, but current analyses were negative (&lt;0.6 BU/mL). Baseline FVIII/FIX activity was similar among NNA positive and negative patients. Current bleeding rates were low, but patients with NNAs captured a higher Hemophilia Joint Health Score (7 [median]; Q1-Q3, 3-20 vs. 4; 1-9) (<em>P</em> = .02) and had more frequently undergone arthroplasty or arthrodesis (5 [33%] vs. 15 [13%]) (<em>P</em> = .03).</div></div><div><h3>Conclusion</h3><div>NNAs were detected in 13% of Nordic persons with MHA and MHB, most frequently after 150 EDs. Patients with NNAs had more severe hemophilic arthropathy than patients without NNAs. The relationship between NNAs and clinical outcome in hemophilia should be further explored in a large cohort including pharmacokinetics and longitudinal observations with repeated blood sampling.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102611"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702285","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":"Maternal thrombocytopenia is not predictive of neonatal thrombocytopenia: a single-center Irish study","authors":"Ligia Nechifor ,&nbsp;Daniel O’Reilly ,&nbsp;John O’Loughlin ,&nbsp;Fionnuala Ní Áinle ,&nbsp;Naomi Mc Callion ,&nbsp;Lyudmyla Zakharchenko","doi":"10.1016/j.rpth.2024.102622","DOIUrl":"10.1016/j.rpth.2024.102622","url":null,"abstract":"<div><h3>Background</h3><div>Maternal thrombocytopenia during pregnancy is common. However, the relationship between maternal and neonatal thrombocytopenia is poorly understood.</div></div><div><h3>Objectives</h3><div>We aimed to determine whether an association exists between platelet counts of neonates born to mothers with moderate-to-severe thrombocytopenia (&lt;100 × 10⁹/L) and neonatal platelet counts.</div></div><div><h3>Methods</h3><div>We identified records from 557 patients with moderate-to-severe thrombocytopenia (maternal platelet count &lt;100 × 10⁹/L) and the 338 associated newborn charts from 2018 to 2022 in a single large maternity center. Pregnant people with a platelet count of &lt;100 × 10⁹/L prior to delivery during present gestation were included. Any thrombocytopenia that occurred outside of pregnancy or in the postpartum period was excluded. A logistic regression was then generated to examine the association between maternal thrombocytopenia and neonatal thrombocytopenia. A receiver operating characteristic (ROC) curve was generated to assess accuracy of (i) lowest maternal platelet count and (ii) trimester of thrombocytopenia onset in predicting neonatal thrombocytopenia.</div></div><div><h3>Results</h3><div>A total of 550 full blood count assessments were taken in neonates of pregnant people with thrombocytopenia. Sixteen neonates with clinically significant thrombocytopenia (platelet count &lt;100 × 10⁹/L) were identified. A binomial logistic regression was fitted that demonstrated limited association between lowest maternal platelet count and trimester of onset of maternal thrombocytopenia and the development of neonatal thrombocytopenia. An ROC curve was generated to determine the accuracy of maternal platelet count at identifying neonatal thrombocytopenia. The coordinates of the best platelet count threshold for this dataset were then derived from the ROC curve and determined that a threshold of 77.5 × 10⁹/L maternal platelets offered the best accuracy.</div></div><div><h3>Conclusion</h3><div>Neonatal full blood count assessment based on maternal platelet counts of &lt;100 × 10⁹/L has a poor diagnostic yield with no statistically significant association in this cohort on logistic regression analysis. A lower threshold of 77.5 × 10⁹/L may be of higher clinical utility and improve laboratory and clinical workflow.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102622"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759315","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":"Efficacy, safety, and quality of life 4 years after valoctocogene roxaparvovec gene transfer for severe hemophilia A in the phase 3 GENEr8-1 trial","authors":"Andrew D. Leavitt ,&nbsp;Johnny Mahlangu ,&nbsp;Priyanka Raheja ,&nbsp;Emily Symington ,&nbsp;Doris V. Quon ,&nbsp;Adam Giermasz ,&nbsp;Maria Fernanda López Fernández ,&nbsp;Gili Kenet ,&nbsp;Gillian Lowe ,&nbsp;Nigel S. Key ,&nbsp;Carolyn M. Millar ,&nbsp;Steven W. Pipe ,&nbsp;Bella Madan ,&nbsp;Sheng-Chieh Chou ,&nbsp;Robert Klamroth ,&nbsp;Jane Mason ,&nbsp;Hervé Chambost ,&nbsp;Flora Peyvandi ,&nbsp;Elaine Majerus ,&nbsp;Dominic Pepperell ,&nbsp;Margareth C. Ozelo","doi":"10.1016/j.rpth.2024.102615","DOIUrl":"10.1016/j.rpth.2024.102615","url":null,"abstract":"<div><h3>Background</h3><div>Valoctocogene roxaparvovec, an adeno-associated virus-mediated gene therapy for severe hemophilia A, enables endogenous factor (F)VIII expression and provides bleed protection.</div></div><div><h3>Objectives</h3><div>Determine valoctocogene roxaparvovec durability, efficacy, and safety 4 years after treatment.</div></div><div><h3>Methods</h3><div>In the phase 3 GENEr8-1 trial, 134 adult male persons with severe hemophilia A without inhibitors and previously using FVIII prophylaxis received a 6 × 10¹³ vg/kg infusion of valoctocogene roxaparvovec. Efficacy endpoints included annualized bleed rate, annualized FVIII infusion rate, FVIII activity, and the Haemophilia-Specific Quality of Life Questionnaire for Adults. Adverse events and immunosuppressant use were assessed. Change from baseline was assessed after participants discontinued prophylaxis (scheduled for week 4).</div></div><div><h3>Results</h3><div>Median follow-up was 214.3 weeks; 2 participants discontinued since the previous data cutoff. Declines from baseline in mean treated annualized bleed rate (−82.6%; <em>P</em> &lt; .0001) and annualized FVIII infusion rate (−95.5%; <em>P</em> &lt; .0001) were maintained from previous years in the primary analysis population of 112 participants who enrolled from a noninterventional study. During year 4, 81 of 110 rollover participants experienced 0 treated bleeds. Week 208 mean and median chromogenic FVIII activity were 16.1 IU/dL and 6.7 IU/dL, respectively, in 130 modified intention-to-treat participants. Seven participants resumed prophylaxis since the previous data cutoff. Mean change from baseline to week 208 in Haemophilia-Specific Quality of Life Questionnaire for Adults Total Score (<em>P</em> &lt; .0001) remained clinically meaningful for modified intention-to-treat participants. Alanine aminotransferase elevation was the most common adverse event during year 4 (56/131 participants); none required immunosuppressants.</div></div><div><h3>Conclusion</h3><div>Valoctocogene roxaparvovec provides persistent FVIII expression, hemostatic control, and health-related quality of life improvements with no new safety signals.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102615"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759316","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 anticoagulant effects of milvexian, a novel small molecule factor XIa inhibitor, are neutralized by activated prothrombin complex concentrates and recombinant factor VIIa in human plasma and whole blood in vitro","authors":"Matthew Bunce,&nbsp;Zheng Huang Devine,&nbsp;Madhu Chintala","doi":"10.1016/j.rpth.2024.102600","DOIUrl":"10.1016/j.rpth.2024.102600","url":null,"abstract":"<div><h3>Background</h3><div>The development of anticoagulants that provide antithrombotic efficacy without a concomitant bleeding risk remains an unmet clinical need in thrombosis. Although direct oral anticoagulants (DOACs) have a reduced incidence of major bleeding compared with warfarin, they still carry a bleeding risk, resulting in a suboptimal therapeutic index. Epidemiologic data suggest that inhibiting activated factor XI (FXIa) may offer an improved safety profile with respect to bleeding risk compared with current-generation DOACs. Additionally, a phase II trial of milvexian in patients undergoing elective total knee replacement demonstrated robust dose-dependent efficacy with no statistically significant increase in bleeding. Nevertheless, the ability to rapidly and effectively correct FXIa inhibitor–induced anticoagulation may still be important in situations where patients experience uncontrolled bleeding or require emergency surgery.</div></div><div><h3>Objectives</h3><div>We assessed the ability to normalize the anticoagulant effects of the novel small-molecule FXIa inhibitor milvexian (BMS-986177/JNJ-70033093) <em>in vitro</em> using commercially available prohemostatic agents.</div></div><div><h3>Methods</h3><div>Milvexian-associated anticoagulation and correction was evaluated in activated partial thromboplastin time clotting assays, thromboelastography, and kaolin-initiated thrombin generation assays.</div></div><div><h3>Results</h3><div>Activated prothrombin complex concentrates (PCCs) and recombinant factor (rF)VIIa corrected the anticoagulant effects of milvexian in activated partial thromboplastin time clotting assays, thromboelastography, and kaolin-initiated thrombin generation assays. In contrast, other agents, including PCCs, rFIX, and rFVIII, demonstrated either modest or no correction of milvexian-associated anticoagulation.</div></div><div><h3>Conclusion</h3><div>This study demonstrated that currently available activated PCCs and rFVIIa normalize the anticoagulation induced by milvexian <em>in vitro</em>. The clinical utility of these agents remains to be established.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102600"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748651","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}