Blood advances最新文献

{"title":"A common TBP-binding site mutation elevates γ-globin levels by competitive globin switching change in β-thalassemia.","authors":"Mengyang Song, Xiaolei Wei, Hualei Luo, Jueheng Wang, Yuhua Ye, Lang Qin, Chao Niu, Yong Long, Xingmin Wang, Congwen Shao, Miao Yu, Feng Gu, Xinhua Zhang, Xiangmin Xu","doi":"10.1182/bloodadvances.2024013695","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024013695","url":null,"abstract":"<p><p>β-thalassemia is a common monogenic disorder caused by genetic defects in β-globin genes (HBB), resulting in imbalanced synthesis of α-/β-globin and ineffective erythropoiesis. It has been well documented that β-thalassemia patients, or even carriers, mostly experience re-activation of fetal hemoglobin (Hb F), but its underlying mechanisms are incompletely understood. We took advantage of a previously established cohort of 1142 β-thalassemia patients with diverse thalassemic mutations subjected to targeted next-generation sequencing. Genotype-phenotype association studies demonstrated that the HBB: c. -78A>G showed a remarkable effect on the elevation of Hb F levels compared to other β-thalassemic mutations. To experimentally validate the conclusion above, the RNP transfection complex through homology-directed repair (HDR) by electroporation was performed, from which we observed a consistent increase of Hb F expression in both HUDEP-2 and primary CD34+ cell lines. Furthermore, ChIP-qPCR, Dual-luciferase reporter assay, and circular chromosome conformation capture (4C) assays validated a decreased occupancy of the HBB TATA-Box by TBP, leading to boosted expression of γ-globin genes by enhanced interaction between locus control regions (LCRs) and γ-globin gene promoters. The patient-based investigation and experimental validations presented in this study might lead to a better understanding of stage-specific globin-gene expression mediated by competitive binding of distal enhancers (LCRs).</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene Therapy for Hemophilia B: Results From the Phase1/2 101HEMB 1/2 Studies.","authors":"Steven W Pipe, Allen Poma, Anita Rajasekhar, Tamara Everington, Serap Sankoh, Jack Allen, Jason Cataldo, Eric Crombez","doi":"10.1182/bloodadvances.2024015184","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024015184","url":null,"abstract":"<p><p>Hemophilia B (HemB) is a rare, X-linked bleeding disorder predominantly affecting males caused by Factor IX (FIX) gene variants leading to spontaneous bleeding and impaired ability to clot following injury or surgeries. Standard-of-care is prophylaxis to increase FIX levels. DTX101 is a non‑replicating, AAV serotype rh10 gene transfer vector containing a codon-optimized wild-type human FIX coding sequence. The Phase 1/2 open-label, single-arm, multicenter, dose-finding 101HEMB01 study (NCT02618915) examined the safety/efficacy of DTX101 in adult males with HemB; the 101HEMB02 follow-up study (NCT02971969) assessed long-term outcomes. Participants received DTX101 as 1.6x1012 genome copies/kg (Cohort 1; N=3) or 5.0x1012 genome copies/kg (Cohort 2; N=3) at baseline and were monitored through Week 44 (Cohort 2)/52 (Cohort 1) (101HEMB01), then 4 additional years (101HEMB02). The primary endpoint of 101HEMB01, peak plasma FIX level at Week 6, showed median (range) levels of 7.0 (5.0,8.0) and 10.0 (6.0,16.0) IU/dL in Cohorts 1 and 2, respectively. Levels failed to reach the 20 IU/dL target criteria; all participants required adjunct FIX replacement therapy based on low FIX activity at intermediate time points. In 101HEMB01, 4/6 participants experienced treatment-related adverse events of elevated transaminase levels (3) and fatigue (1), and 1 experienced fatigue in 101HEMB02; none experienced related serious adverse events. Elevated transaminase levels were asymptomatic and resolved with steroids in all subjects. The DTX101 program was halted for insufficient treatment response; however, from its completion, lessons can be learned regarding the design and execution of gene therapy clinical trials including additional optimization of transgene sequence and immunosuppression protocols.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota restoration with oral pooled fecal microbiotherapy after intensive chemotherapy: the phase Ib CIMON trial.","authors":"Florent Malard, Sylvain Thepot, Thomas Cluzeau, Martin Carre, Delphine Lebon, Pierre Bories, Ollivier Legrand, Marianne Schwarz, Michael Loschi, Mathieu Meunier, Magalie Joris, Cyrielle Gasc, Juliette Jouve, Benoît Levast, Emilie Plantamura, Emmanuel Prestat, Antoine Sabourin, Beatrice Gaugler, Joel Dore, Christian Récher, Mohamad Mohty","doi":"10.1182/bloodadvances.2024015571","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024015571","url":null,"abstract":"<p><p>Intensive chemotherapy (IC) combined with broad-spectrum antibiotics for acute myeloid leukemia (AML) leads to gut microbiota dysbiosis, promoting pathological conditions and an increased incidence of complications, possibly limiting eligibility to allogenic hematopoietic cell transplantation (alloHCT). The purpose of this dose-ranging phase I study (CIMON) was to evaluate the first-in-man use of MaaT033, a pooled, allogeneic, lyophilized, and standardized fecal microbiotherapeutic product, formulated as a delayed-release capsule for oral administration. Primary objectives of the study were to evaluate the maximum tolerable dose of MaaT033 in 21 AML patients having undergone IC and antibiotics. Secondary objectives were to assess MaaT033 safety, its efficacy in restoring the patients' gut microbiome using shotgun sequencing in order to evaluate the recommended dose regimen, and patient compliance (ClinicalTrials.gov number: NCT04150393). MaaT033 was shown to be safe and effective for gut microbiota restoration in AML patients receiving IC and antibiotics, with an excellent gut microbiota reconstruction based on diversity indices at the species level, and restoration of microbial communities close to the composition of the drug product. Moreover, inflammatory markers (C-reactive protein, interleukin-6) decrease with treatment, while short-chain fatty acids increase over time. A randomized, placebo-controlled phase IIb trial, in recipients of alloHCT patients in ongoing.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-glycan shielded CUB domains of ADAMTS13 prevent binding of C-terminal antibodies in patients with immune-mediated TTP.","authors":"Tim Postmus, Nelly Schilder, Juliana Ferreira de Santana, Pieter Langerhorst, Paul Kaijen, Paul Coppo, Bérangère S Joly, Agnès Veyradier, Karen Vanhoorelbeke, Jan Voorberg","doi":"10.1182/bloodadvances.2024014298","DOIUrl":"10.1182/bloodadvances.2024014298","url":null,"abstract":"<p><strong>Abstract: </strong>In immune-mediated thrombotic thrombocytopenic purpura (iTTP), patients develop antibodies against ADAMTS13. Most patients exhibit inhibitory antispacer antibodies. Noninhibitory antibodies binding to the carboxy-terminal CUB domains have been suggested to enhance the clearance of ADAMTS13 in iTTP. Furthermore, anti-CUB antibodies induce an open conformation, which has been shown to be an important biomarker for disease severity and relapse risk. We explored whether the introduction of N-glycans in the CUB domains of ADAMTS13 can reduce the binding of pathogenic anti-CUB autoantibodies. The binding of a panel of anti-CUB monoclonal antibodies derived from patients with iTTP, to newly designed N-glycan modified ADAMTS13 CUB domain variants, was assessed by enzyme-linked immunosorbent assay. In addition, a subset of these variants was screened against plasma samples from patients with iTTP, which primarily contain antibodies directed toward the carboxy-terminal domains of ADAMTS13. Introduction of N-glycans at amino acid positions of 1251, 1255, and 1368 in the CUB1/2 domains of ADAMTS13 can effectively reduce the binding of 6 out of 7 anti-CUB antibodies derived from patients with iTTP. Reduced binding to CUB N-glycan variants was observed in 8 out of 9 patient samples. Binding was decreased from 81% to 47% for NGLY3+CUB-NGLY and 60% to 28% for 5ALA+CUB-NGLY variants. Collectively our findings show that the introduction of N-glycans within the CUB domain of ADAMTS13 can prevent the binding of anti-CUB antibodies in patients with iTTP. Based on these findings, we propose that CUB-NGLY modified ADAMTS13 variants can be used for improved treatment of patients with iTTP.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"1728-1737"},"PeriodicalIF":7.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal analysis of gut microbiome and metabolome correlates of response and toxicity with idecabtagene vicleucel.","authors":"Satabdi Saha, Lubna Rehman, Abdur Rehman, Faezeh Darbaniyan, Donna M Weber, Melody Becnel, Mahmoud R Gaballa, Sheeba K Thomas, Hans C Lee, Chia-Chi Chang, Reetakshi Arora, Meghan Menges, Salvatore Corallo, Marco L Davila, Frederick L Locke, Mark R Tanner, Sattva S Neelapu, Elizabeth J Shpall, Christopher R Flowers, Robert Z Orlowski, Robert R Jenq, Michael D Jain, Christine Peterson, Doris K Hansen, Neeraj Y Saini, Krina K Patel","doi":"10.1182/bloodadvances.2024014476","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024014476","url":null,"abstract":"<p><p>Increasing evidence suggests that the gut microbiome may influence the responses and toxicities associated with chimeric antigen receptor (CAR) therapy. We conducted whole-genome shotgun sequencing on stool samples (n=117) collected at various times from multiple myeloma patients (n=33) undergoing idecabtagene vicleucel (ide-cel) anti-B cell maturation antigen CAR-T therapy. We observed a significant decrease in bacterial diversity post-ide-cel infusion, along with significant differences in bacterial composition linked to therapy response and toxicities. Specifically, we found significant enrichment of Flavonifractor plautii, Bacteroides thetaiotaomicron, Blautia fecis, and Dysosmobacter species in ide-cel responders. A notable finding was the link between major microbiome disruption, defined as dominant specific taxa (greater than 35% prevalence) and increased facultative pathobionts like Enterococcus, with ide-cel toxicities, especially cytokine release syndrome (CRS). Patients with genus dominance in baseline samples had a higher incidence of grade 2 or higher CRS at 46.2% compared to those without genus dominance (11.1%, p=0.043). Additionally, network analysis and mass spectrometric assessment of stool metabolites revealed important associations and pathways, such as Flavonifractor plautii being linked to increased indole metabolites and pathways in responders. Our findings uncover novel microbiome associations between ide-cel responses and toxicities that may be useful for developing modalities to improve CAR-T outcomes.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Agents of shield: glycans mask antibody epitopes on ADAMTS13.","authors":"Colin A Kretz","doi":"10.1182/bloodadvances.2025015862","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025015862","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":"9 7","pages":"1726-1727"},"PeriodicalIF":7.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PD-1 Inhibition for Relapse after Allogeneic Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome.","authors":"John M Magenau, David G Frame, Mary Mansour Riwes, John Joseph Maciejewski, Sarah Anand, Attaphol Pawarode, Anamarija M Perry, Marcus J Geer, Thomas M Braun, Monalisa Ghosh, Pavan Reddy","doi":"10.1182/bloodadvances.2024015200","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024015200","url":null,"abstract":"<p><p>Relapse of AML and MDS remains the primary source of mortality after allogeneic transplantation (HCT). Targeting PD-1 is an approach for reversing T cell exhaustion and restoring the graft-versus-leukemia (GVL) effect that has logistical advantages versus donor lymphocyte infusion. In a prospective phase 1B clinical trial, pembrolizumab monotherapy was administered every three weeks to sixteen AML (n=12) and MDS (n=4) patients in relapse after HCT to assess Graft-versus-Host Disease (GVHD), clinical response and survival. The median time to relapse after HCT was 5.5 months and the median pre-treatment bone marrow blast percentage was 21.5%. The overall response rate (ORR) was 31.3% for patients receiving pembrolizumab monotherapy, consisting of three complete remissions (18.8%) and two partial remissions (13.5%). The median duration of response was 610 days. A significantly greater proportion of patients with mixed CD3 chimerism had clinical response compared to those with full donor chimerism (50% vs. 0%; p=0.03). Immune toxicities were frequent with 37.5% patients developing severe (grade III-IV) GVHD after pembrolizumab, of which the majority had resistance to corticosteroids and contributed to death in four patients (25%). The one-year overall survival was 37.5% and event-free survival was 31.3%. For AML, one-year overall survival was 50.0%. In this trial, PD-1 inhibition led to durable remissions in a third of patients experiencing early relapse after HCT suggesting this approach may augment the GVL response. Responses were exclusively observed in the setting of mixed CD3 donor chimerism. Immune toxicities (GVHD) were a barrier to successful treatment outcome. NCT03286114.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Red Blood Cells with Reduced Deformability are Selectively Cleared from Circulation in a Mouse Model.","authors":"Emel Islamzada, Kerryn Matthews, Erik S Lamoureux, Simon P Duffy, Mark D Scott, Hongshen Ma","doi":"10.1182/bloodadvances.2024014100","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024014100","url":null,"abstract":"<p><p>Donated red blood cells (RBCs) collected for blood transfusions progressively lose their deformability due to natural aging and cold storage in blood bags. This loss accelerates circulatory clearance via mechanical sensing by the spleen, leading to RBC retention and entrapment. While reduced deformability is known to shorten RBC circulation time, the extent to which splenic clearance distinguishes and removes RBCs with altered deformability is poorly understood. Here, we show that sub-populations of donor RBCs with a deformability distribution distinct from endogenous recipient's RBCs are selectively and specifically cleared from circulation within 24 hours of infusion in a mouse model, whereas donor RBCs with a deformability distribution similar to endogenous recipient RBCs persist and undergo normal clearance. We performed this study by treating murine donor RBCs with the mild catalase inhibitor aminotriazole to generate donor RBC with a widened range of deformability. These cells were then fluorescently labeled and infused into syngeneic recipients. Using a microfluidic device capable of deformability-based sorting of RBCs, we concurrently measure the deformability distribution of donor RBCs pre-transfusion and post-transfusion, along with endogenous recipient RBCs. Our findings provide direct evidence that RBCs with deformability profiles distinct from endogenous recipient RBCs are selectively and specifically cleared from circulation.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patients with AML and an IDH2-R172 Mutation Exhibit a Unique Initial Response to Intensive Chemotherapy Induction.","authors":"Meira Yisraeli Salman, Alexander R Terry, Andriy Derkach, David Nemirovsky, Kuo-Kai Chin, Yannis K Valtis, Leora Boussi, Theresa Spivey, Wenbin Xiao, Christopher A Famulare, Jenna R Ciervo, Jacob M Rowe, Martin S Tallman, Eytan M Stein","doi":"10.1182/bloodadvances.2024015324","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024015324","url":null,"abstract":"<p><p>The utility of a mid-cycle bone marrow biopsy (BMB) for early assessment of response in patients with acute myeloid leukemia (AML) after intensive chemotherapy (IC) induction is contested. Even when challenged, there is little consideration as to the possibility of different response dynamics among genetically defined subgroups. Clinical observations led to the hypothesis that patients with AML and mutations in IDH2-R172 (R172-m) exhibit particularly slow blast reduction following IC induction. The purpose of this study was to analyze response kinetics of patients with R172-m to IC and compare the dynamics to patients with AML and IDH2-R140 mutations (R140-m). A retrospective single-center analysis was conducted among patients with newly diagnosed IDH2-mutated AML who received IC induction. Dynamics of blast reduction were compared and correlated with outcomes. 52 patients were identified; 33 with R140-m and 19 with R172-m. Patients with R172-m had significantly higher mid-cycle BMB median blast count (70% versus 5%, p<0.001), and their BMBs were slightly more cellular (p=0.045). Among the R140-m, 58% had ≤5% blasts versus 0 of the R172-m. Furthermore, it took significantly longer for patients with R172-m to achieve blast clearance (≤5% blasts in BMB) compared to those with R140-m (p=0.017). However, there was no difference in overall survival between the two groups, and outcomes were similar and favorable. This type of slow blast reduction has only previously been described in patients with acute promyelocytic leukemia. These findings suggest judicial application of re-induction strategies in this subgroup and warrant further investigation.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Duration of primary/secondary treatment to prevent recurrent venous thromboembolism: a systematic review and meta-analysis.","authors":"Anqi Li, Rasha Khatib, Luciane Cruz Lopes, Fazila Aloweni, Liming Lu, Qingyong He, Jiaming Wu, Peiming Zhang, Yuyuan Tang, Sureka Pavalagantharajah, Nigar Sekercioglu, Carlos A Cuello Garcia, Serge Koujanian, Arnav Agarwal, Sean Alexander Kennedy, Ignacio Neumann, Sam Schulman, Wojtek Wiercioch, Gabriel Rada, Andrew M Peseski, Thomas L Ortel, Yu-Qing Zhang","doi":"10.1182/bloodadvances.2024015371","DOIUrl":"10.1182/bloodadvances.2024015371","url":null,"abstract":"<p><strong>Abstract: </strong>Antithrombotic therapy can prevent recurrent deep vein thrombosis (DVT) and pulmonary embolism (PE). It is, however, associated with an increased risk for major bleeding. This meta-analysis systematically reviewed the evidence regarding the duration of antithrombotic therapy to assess benefits and harms. We systematically searched for randomized controlled trials (RCTs) that compared shorter (3-6 months) with longer (>6 months) courses of anticoagulation for the primary treatment of venous thromboembolism (VTE) or that compared discontinued with indefinite antithrombotic therapy for the secondary prevention of VTE. Pairs of reviewers screened the eligible trials and collected data. This study included 22 RCTs (11 617 participants). Pooled estimates showed that, for the primary treatment of unprovoked VTE, VTE provoked by chronic risk factors or transient risk factors, treating patients with a longer course (>6 months) of anticoagulation, as opposed to a shorter course (3-6 months), probably reduced recurrent PE (risk ratio [RR], 0.66; 95% confidence interval [CI], 0.42-1.02) and DVT (RR, 0.85; 95% CI, 0.63-1.14), but it was associated with increased mortality (RR, 1.43; 95% CI, 0.85-2.41) (moderate certainty) and a higher risk for major bleeding (RR, 2.02; 95% CI, 1.02-3.98; high certainty). For the secondary prevention of unprovoked VTE and VTE provoked by chronic risk factors, when compared with discontinuing treatment, indefinite anticoagulation therapy was associated with decreased mortality (RR, 0.54; 95% CI, 0.36-0.81), a reduction in recurrent PE (RR, 0.25; 95% CI, 0.16-0.41) and DVT (RR, 0.15; 95% CI, 0.10-0.21), and an increase in the risk for bleeding (RR, 1.98; 95% CI, 1.18-3.30), all supported by high certainty. Indefinite antiplatelet therapy may be associated with decreased mortality (RR, 0.95; 95% CI: 0.53-1.68; low certainty), probably a reduction in recurrent PE (RR, 0.65; 95% CI, 0.41-1.03) and DVT (RR, 0.44; 95% CI, 0.17-1.13) (moderate certainty), and may increase the risk for bleeding (RR, 1.28; 95% CI, 0.48-3.41; low certainty). In summary, for the primary treatment of all types of VTE, shorter (3-6 months) duration of anticoagulation is more beneficial. For the secondary prevention of unprovoked VTE or VTE provoked by chronic risk factors, indefinite antithrombotic treatment is more beneficial.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":"9 7","pages":"1742-1761"},"PeriodicalIF":7.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}