Blood Vessels, Thrombosis & Hemostasis最新文献

{"title":"Cellular and enzymatic features of thrombi in humans are vascular bed dependent","authors":"Matthew T. Bender ∗ ,&nbsp;Anu Aggarwal ∗ ,&nbsp;Matthew Godwin ,&nbsp;Suman Guntupalli ,&nbsp;Aravinda Nanjundappa ,&nbsp;Leben Tefera ,&nbsp;Ihab Haddadin ,&nbsp;Michael Tong ,&nbsp;William M. Baldwin III ,&nbsp;Robert L. Fairchild ,&nbsp;Marcelo Gomes ,&nbsp;Joseph Campbell ,&nbsp;David Schumick ,&nbsp;Pulkit Chaudhury ,&nbsp;Doran Mix ,&nbsp;Scott J. Cameron","doi":"10.1016/j.bvth.2024.100029","DOIUrl":"10.1016/j.bvth.2024.100029","url":null,"abstract":"<div><h3>Abstract</h3><div>Mechanisms behind vascular remodeling following thrombosis are unclear. Although acute arterial thrombosis in the cerebrovascular circulation has devastating consequences and requires immediate attention, the management of venous thromboembolism (VTE) varies significantly. Our goal was to determine the molecular signatures and cellular content of thrombus extracted using a catheter to gain insight into vascular remodeling. Twenty-five patients underwent catheter-directed thrombectomy (CDT); 13 for cerebrovascular accident (CVA), 8 for pulmonary embolism, and 4 for deep vein thrombosis. Protein and RNA were extracted from thrombi to enable immunoblotting, RNA sequencing, and quantification of gene expression. The time from symptom onset to thrombus extraction was 7.7 ± 1.9 hours for CVA and 109 ± 55 hours for VTE. Protein concentration, white blood cell content (monocytes), and red blood cell content were greater in venous thrombus than in arterial thrombus, whereas the platelet content was similar. Both venous and arterial thrombi contained several zinc endopeptidases belonging to the matrix metalloproteinase (MMP) family. MMP9 activity in venous thrombus was greater than arterial thrombus (61 ± 9 ng/mL per μg protein vs 25 ± 6 ng/mL per μg protein; <em>P</em> = .005). Arterial and venous thrombi displayed surprisingly different phenotypes, with biologically active enzymes promoting blood vessel remodeling and enzymatic activity proportional to thrombus age extracted from the veins. These mechanistic data may support the role of early CDT in venous circulation to avoid irreversible vascular remodeling.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 1","pages":"Article 100029"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143093759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of azathioprine in the management of ITP in the TPO-RA era: a single-center retrospective study","authors":"Alexandre Le-Nguyen ,&nbsp;Shamim Mortuza ,&nbsp;Cyrus C. Hsia","doi":"10.1016/j.bvth.2024.100035","DOIUrl":"10.1016/j.bvth.2024.100035","url":null,"abstract":"<div><h3>Abstract</h3><div>Access to modern therapeutics for immune thrombocytopenia (ITP), such as thrombopoietin-receptor agonists (TPO-RAs), remains a challenge, limiting clinicians’ options. We investigated azathioprine in relapsed/refractory ITP to determine its efficacy and safety, focusing on evaluating its utility in post–TPO-RA patients. We retrospectively reviewed all adult patients, aged ≥18 years, who were worked up for thrombocytopenia between 2009 and 2022 at a tertiary care center in Ontario, Canada. Only patients with ITP treated with azathioprine were included. We identified 92 patients with ITP who received azathioprine, with a mean age of 55.6 ± 22.3 years; 53 were females and 39 males, with 64 having primary ITP. The overall response rate (ORR) was 47.8% (44/92), with a sustained response rate of 77.3% (34/44) at 6 months. The median time to response was 6 weeks. Fourteen patients (31.8%) relapsed, with a median duration of response of 10 weeks. Most patients (73.9%) had documented side effects, with nausea/vomiting, infections, and myelosuppression being the most common. The majority of patients received azathioprine as third-line therapy; 6 patients after TPO-RA and 27 after splenectomy. ORR was 50.0% (3/6) and 40.7% (11/27) in each group, respectively. This is the largest retrospective study, to our knowledge, demonstrating benefit with azathioprine in relapsed/refractory ITP. Its efficacy remains consistent both after TPO-RA (<em>P</em> = .948) and after splenectomy (<em>P</em> = .259), offering clinicians a comparable drug response irrespective of prior TPO-RA exposure or splenectomy. We propose that azathioprine remains a viable option for relapsed/refractory ITP in the TPO-RA era.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 1","pages":"Article 100035"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143093713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunothrombosis and plasma fibrinolytic function for pediatric COVID-19: a secondary analysis from the COVAC-TP trial","authors":"Anthony A. Sochet ,&nbsp;Austin R. Sellers ,&nbsp;Marisol Betensky ,&nbsp;John M. Morrison ,&nbsp;Dina Ashour ,&nbsp;Jamie L. Fierstein ,&nbsp;Ernest K. Amankwah ,&nbsp;Steven Bruzek ,&nbsp;Vera Ignjatovic ,&nbsp;Neil A. Goldenberg ,&nbsp;COVID-19 Anticoagulation in Children–Thromboprophylaxis Trial Investigators","doi":"10.1016/j.bvth.2024.100038","DOIUrl":"10.1016/j.bvth.2024.100038","url":null,"abstract":"<div><h3>Abstract</h3><div>The relationship between fibrinolysis, inflammation, and prothrombotic risk among children hospitalized for coronavirus disease 2019 (COVID-19)–related illness is ill defined. To investigate the association between plasma fibrinolytic capacity and proinflammatory cytokine concentrations among children hospitalized for primary COVID-19 infection and multisystem inflammatory syndrome in children (MIS-C), we hypothesized that cytokine concentrations differ by clinical phenotype and are associated with hypofibrinolysis. We analyzed banked plasma specimens serially collected from children aged &lt;18 years admitted for primary COVID-19 or MIS-C and enrolled in the COVID-19 Anticoagulation in Children–Thromboprophylaxis multicenter trial, an open-label, multicenter, phase 2 clinical trial conducted between July 2020 and May 2021. Plasma coagulative and fibrinolytic function were measured via the clot formation and lysis (CloFAL) assay and modified mini-euglobulin clot lysis assay (ECLA). Interleukin-1β (IL-1β), IL-6, and IL-8, and tumor necrosis factor α were measured by the Meso Scale Discovery assay. Correlations were evaluated using Spearman rank testing. A total of 132 banked plasma specimens from 38 participants (COVID-19: n = 18; MIS-C: n = 20) were analyzed. Overall, increased coagulative function (ie, elevated CloFAL area under the curve) and impaired fibrinolytic function (ie, reduced CloFAL fibrinolytic index [FI] and elevated modified mini-ECLA clot lysis time ratio [CLTR]) were observed but most notably among those with MIS-C. Plasma cytokine concentrations correlated with assay indices of hypofibrinolysis (ie, modified mini-ECLA CLTR and CloFAL FI). In summary, among children hospitalized for COVID-19–related illness, hypercoagulability and hypofibrinolysis are mediated, in part, by inflammation that may contribute to prothrombotic risk. This trial was registered at <span><span>www.ClinicalTrials.gov</span><svg><path></path></svg></span> as #NCT04354155.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 1","pages":"Article 100038"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143093758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic endothelial inflammation in PWH leads to reduced circulating megakaryocyte progenitor cells","authors":"Tong Li ,&nbsp;Colleen Hadigan ,&nbsp;Jaeil Ahn ,&nbsp;Chinmayee Mehta ,&nbsp;Makheni Jean Pierre ,&nbsp;Danial Mahmood ,&nbsp;Metin Ozdemirli ,&nbsp;Cooper James ,&nbsp;Princy Kumar ,&nbsp;Marta Catalfamo","doi":"10.1016/j.bvth.2024.100039","DOIUrl":"10.1016/j.bvth.2024.100039","url":null,"abstract":"","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 1","pages":"Article 100039"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143093753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening for gene variants causing inherited platelet disorders: are the cons always cons?","authors":"Loredana Bury ,&nbsp;Emanuela Falcinelli ,&nbsp;Anna Maria Mezzasoma ,&nbsp;Giulia Ciarrocca Taranta ,&nbsp;Elisa Giglio ,&nbsp;Caterina Matteucci ,&nbsp;Roberta La Starza ,&nbsp;Alessandra Carotti ,&nbsp;Paolo Gresele","doi":"10.1016/j.bvth.2024.100043","DOIUrl":"10.1016/j.bvth.2024.100043","url":null,"abstract":"","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 1","pages":"Article 100043"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143093754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unfolded von Willebrand factor binds protein S and reduces anticoagulant activity","authors":"Martha M. S. Sim ,&nbsp;Molly Y. Mollica ,&nbsp;Hammodah R. Alfar ,&nbsp;Melissa Hollifield ,&nbsp;Dominic W. Chung ,&nbsp;Xiaoyun Fu ,&nbsp;Siva Gandhapudi ,&nbsp;Daniëlle M. Coenen ,&nbsp;Kanakanagavalli Shravani Prakhya ,&nbsp;Dlovan F. D Mahmood ,&nbsp;Meenakshi Banerjee ,&nbsp;Chi Peng ,&nbsp;Xian Li ,&nbsp;Alice C. Thornton ,&nbsp;James Z. Porterfield ,&nbsp;Jamie L. Sturgill ,&nbsp;Gail A. Sievert ,&nbsp;Marietta Barton-Baxter ,&nbsp;Ze Zheng ,&nbsp;Kenneth S. Campbell ,&nbsp;Jeremy P. Wood","doi":"10.1016/j.bvth.2024.100030","DOIUrl":"10.1016/j.bvth.2024.100030","url":null,"abstract":"<div><h3>Abstract</h3><div>The critical plasma anticoagulant protein S (PS) circulates in 2 functionally distinct pools: free (anticoagulant) or bound to complement component 4b-binding protein (C4BP; anti-inflammatory). Acquired free PS deficiency is detected in several viral infections, but its cause is unclear. Here, we used biochemical approaches and human patient plasma samples to identify an interaction between PS and von Willebrand factor (VWF), which causes free PS deficiency and reduced PS anticoagulant activity. We first identified a shear-dependent interaction between PS and VWF by mass spectrometry. Consistently, PS and VWF could be crosslinked together in plasma, and plasma PS and VWF comigrated in gel electrophoresis. The PS/VWF interaction was blocked by and tissue factor pathway inhibitor but not activated protein C, suggesting an interaction with the sex hormone binding globulin region of PS. Microfluidic systems demonstrated that PS stably binds VWF as VWF unfolds under turbulent flow. PS/VWF complexes also localized to platelet thrombi under laminar arterial flow. In thrombin generation–based assays, shearing plasma decreased PS activity, an effect not seen in the absence of VWF. Finally, free PS deficiency in patients with COVID-19 correlated with changes in VWF, but not C4BP, and with thrombin generation. Our data indicate that PS binds to a shear-exposed site on VWF, thus sequestering free PS and decreasing its anticoagulant activity, which would account for the increased thrombin generation potential. Because many viral infections present with free PS deficiency, elevated circulating VWF, and increased vascular shear, we propose that the PS/VWF interaction reported here is a likely contributor to virus-associated thrombotic risk.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 1","pages":"Article 100030"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143093712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo neuroprotection in ischemic stroke by activated protein C requires β-arrestin 2","authors":"Biao Xiang ∗ ,&nbsp;Yaoming Wang ∗ ,&nbsp;Ruslan Rust ,&nbsp;Kassandra Kisler ,&nbsp;William J. Mack ,&nbsp;José A. Fernández ,&nbsp;Berislav V. Zlokovic † ,&nbsp;John H. Griffin †","doi":"10.1016/j.bvth.2024.100037","DOIUrl":"10.1016/j.bvth.2024.100037","url":null,"abstract":"<div><h3>Abstract</h3><div>The protease activated protein C (APC) and its variants provide neuroprotection for murine ischemic stroke and mortality reduction for murine sepsis. For these actions, APC’s in vivo mechanism of action, similar to in vitro studies using cultured cells, involves protease activated receptor 1 (PAR1)–mediated biased signaling. APC/PAR1 signaling in vitro requires β-arrestin 2, an intracellular scaffold protein, and β-arrestin 2–initiated signaling can alter diverse intracellular signaling pathways. This study used a proximal transient middle cerebral artery occlusion model to study the neuroprotective actions of the signaling-selective APC variant, 3K3A-APC, in β-arrestin 2–deficient (<em>Arrb2</em>^–/–) mice. Based on quantitation of brain injuries, 3K3A-APC significantly limited brain injury in control mice to relatively small, localized areas, whereas 3K3A-APC’s protection was lost in <em>Arrb2</em>^–/– mice. Thus, the major in vitro mechanism of action that requires β-arrestin 2 for APC/PAR1 biased signaling is central to the in vivo mechanism of action for APC’s neuroprotection.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 1","pages":"Article 100037"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143093755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low incidence of thromboembolism with Fiix-monitored warfarin compared to conventional warfarin and DOACs in patients with AF","authors":"Arnar B. Ingason ,&nbsp;Brynja R. Gudmundsdottir ,&nbsp;Ragnar Palsson ,&nbsp;Johann P. Hreinsson ,&nbsp;Sigrun H. Lund ,&nbsp;Loic R. Letertre ,&nbsp;Edward Rumba ,&nbsp;Arnar S. Agustsson ,&nbsp;Einar S. Bjornsson ,&nbsp;Pall T. Onundarson","doi":"10.1016/j.bvth.2025.100056","DOIUrl":"10.1016/j.bvth.2025.100056","url":null,"abstract":"<div><h3>Abstract</h3><div>Mixed population studies suggest that monitoring only coagulation factors II and X (Fiix) instead of conventional prothrombin time improves clinical outcomes in patients on warfarin. We hypothesized that Fiix-monitored warfarin (Fiix-warfarin) provides better real-world clinical outcomes than PT based international normalized ratio (PT-INR) monitored warfarin (PT-warfarin), apixaban, dabigatran, and rivaroxaban in non-valvular atrial fibrillation (AF) patients. We performed a retrospective population cohort study over a 5-year period including all long-term orally anticoagulated adult AF patients in the Greater Reykjavik area. Baseline characteristics differences were adjusted using inverse probability of treatment weighting. Principal outcomes were rates of total thromboembolism (TE), all-cause death, and major bleeding. Outcomes with Fiix-warfarin were used as reference. The study population consisted of 6417 patients anticoagulated long-term for 12 914 person-years (py), ie, Fiix-warfarin (n = 1257/py = 2514), PT-warfarin (n = 1904/py = 3998), apixaban (n = 1171/py = 1639), rivaroxaban (n = 1536/py = 3226) or dabigatran (n = 549/py = 1537). PT-warfarin (1.9% per py; hazard ratio (HR) 1.86 [<em>P</em> =.007]), apixaban (1.9% ppy; HR 1.94 [<em>P</em> = .02]), and dabigatran (2.2% ppy; HR 2.19 [<em>P</em> = .01]) had higher TE rates of than Fiix-warfarin (1.1% ppy). Similarly, rivaroxaban trended towards higher TE rates (1.6% ppy; HR 1.58; [<em>P</em> = .07]). Rivaroxaban had significantly higher all-cause mortality rate than Fiix-warfarin (3.0% vs 2.0% ppy; HR 1.48; [<em>P</em> =.04]). Major bleeding rates were similar. Warfarin anticoagulation variability was lower with Fiix-monitoring than with PT-monitoring. We conclude that Fiix-monitored warfarin could be the most effective long-term oral anticoagulant for patients with AF.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 2","pages":"Article 100056"},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analyzing 6211 unique variants in the upgraded interactive FVIII web database reveals novel insights into hemophilia A","authors":"Emily H. T. Print ,&nbsp;Anna M. Simmons ,&nbsp;Holly J. Spencer ,&nbsp;Christos Efthymiou ,&nbsp;Victoria A. Harris ,&nbsp;Stephen J. Perkins","doi":"10.1016/j.bvth.2025.100053","DOIUrl":"10.1016/j.bvth.2025.100053","url":null,"abstract":"<div><h3>Abstract</h3><div>Hemophilia A is a rare genetic disease that occurs with mild, moderate, or severe phenotypes and involves dysfunctional or reduced amounts of plasma factor VIII (FVIII). Identifying causal genetic variants in the <em>F8</em> gene is vital for patient care. Our original interactive MySQL database for FVIII in 2013 presented clinical data on 2014 unique FVIII variants in 5072 patients. Here, we expand our database almost threefold with a new total of 6211 unique FVIII variants in 10 064 patients, spanning 1529 of the 2351 FVIII residues (65%). We have also developed a new full-length FVIII structural model that incorporates both its crystal structure and its disordered B domain, which is not visible in available experimental structures. This enabled the assessment of these variants on FVIII. Of the 6211 unique <em>F8</em> variants identified, 730 (12%) were associated with mild phenotypes, 526 (8%) with moderate phenotypes, 2509 (39%) with severe phenotypes, 53 (1%) with multiple severities, and 2393 (40%) with unreported phenotypes. Most variants occurred in the disordered B domain (1281 variants), followed by the A1, A2, and A3 domains (1130, 1071, and 923 variants, respectively) and the C1 and C2 domains (442 and 439 variants, respectively). Inhibitors were associated with 451 variants (7%). Our new structural analyses often revealed changes to the residue solvent surface accessibilities caused by many FVIII variants. The FVIII variant analyses are supported by similar observations in the structurally related FV protein. Our web-accessible FVIII database will enable easier and improved clinical analyses of FVIII genetic variants.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 3","pages":"Article 100053"},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144571321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kinetics of DNases after hematopoietic stem cell transplant","authors":"Azada Ibrahimova ,&nbsp;Nathan Luebbering ,&nbsp;Lucille Langenberg ,&nbsp;Sheyar Abdullah ,&nbsp;Lauren Strecker ,&nbsp;Kelly E. Lake ,&nbsp;Adam Lane ,&nbsp;Aaron Webster ,&nbsp;Kasiani C. Myers ,&nbsp;Sonata Jodele ,&nbsp;Stella M. Davies","doi":"10.1016/j.bvth.2025.100055","DOIUrl":"10.1016/j.bvth.2025.100055","url":null,"abstract":"<div><h3>Abstract</h3><div>The entire hematopoietic system is rapidly lysed over 8 to 10 days during hematopoietic stem cell transplant (HSCT), releasing toxic intracellular molecules such as cell-free DNA (cfDNA) and proteins such as actin into the circulation. Neutrophil extracellular traps released at the time of engraftment also contribute to the cfDNA burden. Clearance of cfDNA is essential for limiting tissue toxicity. We measured levels of cfDNA, DNase I and DNase1L3 in 108 consecutive patients receiving allogeneic HSCT at baseline and on days 0, 7, 14, 30, and 100. cfDNA levels peak at day 14 and are higher in patients with endothelial injury. DNase I levels are depleted on day 7, recovering quickly by day 14, and remain above baseline at day 100. DNase1L3 levels decreased below baseline at day 0, reached a nadir by day 7, but recovered by day 30 remaining above baseline at day 100. Patients with a periengraftment oxygen requirement and those with transplant-associated thrombotic microangiopathy had higher DNase I levels than those without. DNase1L3 levels did not influence any HSCT outcomes. We analyzed DNase I activity using plasmid DNA degradation and showed decreased activity on days 0 and 7, in agreement with reduced protein levels. Further studies are needed to understand the dynamics of DNases in patients undergoing HSCT, to assess their potential role in HSCT toxicities.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 2","pages":"Article 100055"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143687950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}