{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:44:05Z","timestamp":1791218645766,"version":"4.1.0"},"reference-count":114,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7,3]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>Venous thromboembolism, which includes deep vein thrombosis (DVT) and pulmonary embolism, is a common cardiovascular disorder associated with significant morbidity and mortality. Current treatment options primarily involve anticoagulants, which reduce the risk of fatal events and DVT recurrence but increase the risk of bleeding, particularly in people requiring prolonged thromboprophylaxis. Growing evidence characterizes DVT as a complex inflammation-driven process rather than a merely coagulation-dependent thrombosis, with endothelial cells, neutrophils, and platelets playing major roles in its initiation. Recent studies demonstrate that these cell types undergo profound metabolic reprogramming in response to stasis, hypoxia, and inflammatory stimuli, including shifts in glycolysis, the pentose phosphate pathway, and redox balance. This review summarizes current insights into these metabolic adaptations, examines evidence from preclinical DVT models showing that targeting metabolic pathways can reduce venous thrombus formation without impairing hemostasis, and highlights potential metabolic targets for intervention. By modulating metabolic pathways that underlie the prothrombotic and proinflammatory phenotypes, it may be possible to prevent DVT initiation or limit its progression while reducing the reliance on anticoagulants and the risk of associated bleeding complications. This metabolism-centered perspective opens new avenues for the development of safer, more effective treatments for DVT.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2024027636","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T20:08:04Z","timestamp":1742933284000},"page":"29-40","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":20,"title":["Metabolic pathways in deep vein thrombosis: a new frontier for therapeutic intervention"],"prefix":"10.1182","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6652-2667","authenticated-orcid":false,"given":"Ivan","family":"Budnik","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine, the University of Iowa, Iowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2477-3011","authenticated-orcid":false,"given":"Mariia","family":"Kumskova","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine, the University of Iowa, Iowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8554-0898","authenticated-orcid":false,"given":"Anil K.","family":"Chauhan","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine, the University of Iowa, Iowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"8","key":"2025070311221658800_bib1","first-page":"e93","article-title":"Heart disease and stroke statistics-2023 update: a report from the American Heart Association [published correction appears in Circulation. 2023;148(4):e4]","volume":"147","author":"Tsao","year":"2023","journal-title":"Circulation"},{"key":"2025070311221658800_bib2","doi-asserted-by":"crossref","first-page":"1076029620941077","DOI":"10.1177\/1076029620941077","article-title":"Deep venous thrombosis recurrence and its predictors at selected tertiary hospitals in Ethiopia: a prospective cohort study","volume":"26","author":"Mulatu","year":"2020","journal-title":"Clin Appl Thromb Hemost"},{"issue":"4","key":"2025070311221658800_bib3","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1097\/SLA.0b013e3181d568db","article-title":"Recurrent deep vein thrombosis: long-term incidence and natural history","volume":"251","author":"Labropoulos","year":"2010","journal-title":"Ann Surg"},{"issue":"4","key":"2025070311221658800_bib4","first-page":"CD010956","article-title":"Oral direct thrombin inhibitors or oral factor Xa inhibitors versus conventional anticoagulants for the treatment of deep vein thrombosis","volume":"4","author":"Wang","year":"2023","journal-title":"Cochrane Database Syst Rev"},{"issue":"19","key":"2025070311221658800_bib5","doi-asserted-by":"crossref","first-page":"4693","DOI":"10.1182\/bloodadvances.2020001830","article-title":"American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism","volume":"4","author":"Ortel","year":"2020","journal-title":"Blood Adv"},{"issue":"8","key":"2025070311221658800_bib6","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.it.2018.04.010","article-title":"Immune factors in deep vein thrombosis initiation","volume":"39","author":"Budnik","year":"2018","journal-title":"Trends Immunol"},{"issue":"1","key":"2025070311221658800_bib7","doi-asserted-by":"crossref","first-page":"7831","DOI":"10.1038\/s41467-024-52262-0","article-title":"Integrated landscape of plasma metabolism and proteome of patients with post-traumatic deep vein thrombosis","volume":"15","author":"Zhang","year":"2024","journal-title":"Nat Commun"},{"issue":"3","key":"2025070311221658800_bib8","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1177\/02683555231215199","article-title":"Metabolomic profiling of deep vein thrombosis","volume":"39","author":"Jiang","year":"2024","journal-title":"Phlebology"},{"issue":"8","key":"2025070311221658800_bib9","doi-asserted-by":"crossref","first-page":"495","DOI":"10.3390\/metabo11080495","article-title":"Metabolomic profile in venous thromboembolism (VTE)","volume":"11","author":"Franczyk","year":"2021","journal-title":"Metabolites"},{"issue":"5","key":"2025070311221658800_bib10","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.ejvs.2018.01.027","article-title":"Deep vein thrombosis exhibits characteristic serum and vein wall metabolic phenotypes in the inferior vena cava ligation mouse model","volume":"55","author":"Sung","year":"2018","journal-title":"Eur J Vasc Endovasc Surg"},{"issue":"1","key":"2025070311221658800_bib11","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1146\/annurev-physiol-012110-142305","article-title":"Venous valvular stasis\u2013associated hypoxia and thrombosis: what is the link?","volume":"73","author":"Bovill","year":"2011","journal-title":"Annu Rev Physiol"},{"key":"2025070311221658800_bib12","doi-asserted-by":"crossref","first-page":"524","DOI":"10.3389\/fphys.2018.00524","article-title":"Endothelial mechanotransduction, redox signaling and the regulation of vascular inflammatory pathways","volume":"9","author":"Chatterjee","year":"2018","journal-title":"Front Physiol"},{"issue":"6","key":"2025070311221658800_bib13","doi-asserted-by":"crossref","first-page":"689","DOI":"10.3390\/antiox13060689","article-title":"Oxidative status, iron plasma levels in venous thrombosis patients","volume":"13","author":"Signorelli","year":"2024","journal-title":"Antioxidants (Basel)"},{"issue":"1","key":"2025070311221658800_bib14","first-page":"176","article-title":"Oxidative status and antioxidant enzyme levels in deep venous thrombosis patients","volume":"11","author":"T\u00fcrker","year":"2021","journal-title":"Am J Cardiovasc Dis"},{"issue":"4","key":"2025070311221658800_bib15","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1084\/jem.20112322","article-title":"Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo","volume":"209","author":"von Br\u00fchl","year":"2012","journal-title":"J Exp Med"},{"issue":"5663","key":"2025070311221658800_bib16","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1126\/science.1092385","article-title":"Neutrophil extracellular traps kill bacteria","volume":"303","author":"Brinkmann","year":"2004","journal-title":"Science"},{"issue":"36","key":"2025070311221658800_bib17","doi-asserted-by":"crossref","first-page":"15880","DOI":"10.1073\/pnas.1005743107","article-title":"Extracellular DNA traps promote thrombosis","volume":"107","author":"Fuchs","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"2025070311221658800_bib18","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1038\/nm.2053","article-title":"Extracellular histones are major mediators of death in sepsis","volume":"15","author":"Xu","year":"2009","journal-title":"Nat Med"},{"issue":"6","key":"2025070311221658800_bib19","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1111\/jth.12571","article-title":"Neutrophil extracellular traps form predominantly during the organizing stage of human venous thromboembolism development","volume":"12","author":"Savchenko","year":"2014","journal-title":"J Thromb Haemost"},{"issue":"1","key":"2025070311221658800_bib20","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/j.1538-7836.2011.04544.x","article-title":"Neutrophil extracellular traps promote deep vein thrombosis in mice","volume":"10","author":"Brill","year":"2012","journal-title":"J Thromb Haemost"},{"issue":"21","key":"2025070311221658800_bib21","doi-asserted-by":"crossref","first-page":"8674","DOI":"10.1073\/pnas.1301059110","article-title":"Neutrophil histone modification by peptidylarginine deiminase 4 is critical for deep vein thrombosis in mice","volume":"110","author":"Martinod","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"2025070311221658800_bib22","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/s13018-021-02274-z","article-title":"Rivaroxaban versus aspirin in prevention of venous thromboembolism following total joint arthroplasty or hip fracture surgery: a meta-analysis","volume":"16","author":"Hu","year":"2021","journal-title":"J Orthop Surg Res"},{"issue":"4","key":"2025070311221658800_bib23","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1182\/blood-2010-05-287623","article-title":"von Willebrand factor\u2013mediated platelet adhesion is critical for deep vein thrombosis in mouse models","volume":"117","author":"Brill","year":"2011","journal-title":"Blood"},{"issue":"14","key":"2025070311221658800_bib24","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1182\/blood-2016-09-742999","article-title":"Mice with a deficiency in CLEC-2 are protected against deep vein thrombosis","volume":"129","author":"Payne","year":"2017","journal-title":"Blood"},{"issue":"8","key":"2025070311221658800_bib25","doi-asserted-by":"crossref","first-page":"584","DOI":"10.3109\/08916934.2012.719946","article-title":"Circulating platelets as a source of the damage-associated molecular pattern HMGB1 in patients with systemic sclerosis","volume":"45","author":"Maugeri","year":"2012","journal-title":"Autoimmunity"},{"issue":"20","key":"2025070311221658800_bib26","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.1182\/blood-2016-04-710632","article-title":"Disulfide HMGB1 derived from platelets coordinates venous thrombosis in mice","volume":"128","author":"Stark","year":"2016","journal-title":"Blood"},{"key":"2025070311221658800_bib27","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.thromres.2024.03.005","article-title":"Platelet factor 4 promotes deep venous thrombosis by regulating the formation of neutrophil extracellular traps","volume":"237","author":"Li","year":"2024","journal-title":"Thromb Res"},{"issue":"6487","key":"2025070311221658800_bib28","doi-asserted-by":"crossref","first-page":"eaaw5473","DOI":"10.1126\/science.aaw5473","article-title":"Metabolic reprogramming and cancer progression","volume":"368","author":"Faubert","year":"2020","journal-title":"Science"},{"issue":"2","key":"2025070311221658800_bib29","first-page":"129","article-title":"Metabolic reprogramming, questioning, and implications for cancer","volume":"10","author":"Jacquet","year":"2021","journal-title":"Biology (Basel)"},{"issue":"10","key":"2025070311221658800_bib30","doi-asserted-by":"crossref","first-page":"2000058","DOI":"10.1002\/bies.202000058","article-title":"Metabolic reprogramming is a hallmark of metabolism itself","volume":"42","author":"Medina","year":"2020","journal-title":"Bioessays"},{"key":"2025070311221658800_bib31","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2024.11.004","article-title":"Intracellular endothelial cell metabolism in vascular function and dysfunction","author":"Citrin","year":"12  2024","journal-title":"Trends Endocrinol Metab"},{"issue":"18","key":"2025070311221658800_bib32","doi-asserted-by":"crossref","first-page":"4833","DOI":"10.1016\/j.cell.2024.07.012","article-title":"A systems view of the vascular endothelium in health and disease","volume":"187","author":"Augustin","year":"2024","journal-title":"Cell"},{"issue":"3","key":"2025070311221658800_bib33","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1002\/dvdy.21472","article-title":"Primary cilia sensitize endothelial cells for fluid shear stress","volume":"237","author":"Hierck","year":"2008","journal-title":"Dev Dyn"},{"issue":"1","key":"2025070311221658800_bib34","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1172\/JCI24787","article-title":"Integration of flow-dependent endothelial phenotypes by Kruppel-like factor 2","volume":"116","author":"Parmar","year":"2006","journal-title":"J Clin Invest"},{"issue":"5","key":"2025070311221658800_bib35","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1182\/blood-2002-01-0046","article-title":"Prolonged fluid shear stress induces a distinct set of endothelial cell genes, most specifically lung Kr\u00fcppel-like factor (KLF2)","volume":"100","author":"Dekker","year":"2002","journal-title":"Blood"},{"issue":"1","key":"2025070311221658800_bib36","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1161\/ATVBAHA.114.304277","article-title":"Laminar shear stress inhibits endothelial cell metabolism via KLF2-mediated repression of PFKFB3","volume":"35","author":"Doddaballapur","year":"2015","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"6","key":"2025070311221658800_bib37","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1161\/CIRCULATIONAHA.111.030775","article-title":"NADPH oxidase 4 promotes endothelial angiogenesis through endothelial nitric oxide synthase activation","volume":"124","author":"Craige","year":"2011","journal-title":"Circulation"},{"issue":"4","key":"2025070311221658800_bib38","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1089\/ars.2008.2220","article-title":"NADPH oxidase-dependent signaling in endothelial cells: role in physiology and pathophysiology","volume":"11","author":"Frey","year":"2009","journal-title":"Antioxid Redox Signal"},{"key":"2025070311221658800_bib39","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.nucmedbio.2016.10.006","article-title":"Reactive oxygen species-driven HIF1\u03b1 triggers accelerated glycolysis in endothelial cells exposed to low oxygen tension","volume":"45","author":"Paik","year":"2017","journal-title":"Nucl Med Biol"},{"issue":"4","key":"2025070311221658800_bib40","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/cdd.2008.10","article-title":"Role and regulation of prolyl hydroxylase domain proteins","volume":"15","author":"Fong","year":"2008","journal-title":"Cell Death Differ"},{"key":"2025070311221658800_bib41","doi-asserted-by":"crossref","first-page":"e25217","DOI":"10.7554\/eLife.25217","article-title":"HIF-1\u03b1 is required for disturbed flow-induced metabolic reprogramming in human and porcine vascular endothelium","volume":"6","author":"Wu","year":"2017","journal-title":"Elife"},{"issue":"1","key":"2025070311221658800_bib42","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1161\/CIRCRESAHA.120.318805","article-title":"Immunometabolic endothelial phenotypes: integrating inflammation and glucose metabolism","volume":"129","author":"Xiao","year":"2021","journal-title":"Circ Res"},{"issue":"1","key":"2025070311221658800_bib43","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1007\/s10753-018-0880-x","article-title":"The glycolytic enzyme PFKFB3 controls TNF-\u03b1-induced endothelial proinflammatory responses","volume":"42","author":"Zhang","year":"2019","journal-title":"Inflammation"},{"issue":"6","key":"2025070311221658800_bib44","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.ccell.2016.10.006","article-title":"Inhibition of the glycolytic activator PFKFB3 in endothelium induces tumor vessel normalization, impairs metastasis, and improves chemotherapy","volume":"30","author":"Cantelmo","year":"2016","journal-title":"Cancer Cell"},{"issue":"3","key":"2025070311221658800_bib45","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.cell.2013.06.037","article-title":"Role of PFKFB3-driven glycolysis in vessel sprouting","volume":"154","author":"De Bock","year":"2013","journal-title":"Cell"},{"issue":"1","key":"2025070311221658800_bib46","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1124\/mol.107.038851","article-title":"Enhancement of glucose transporter expression of brain endothelial cells by vascular endothelial growth factor derived from glioma exposed to hypoxia","volume":"73","author":"Yeh","year":"2008","journal-title":"Mol Pharmacol"},{"issue":"3","key":"2025070311221658800_bib47","doi-asserted-by":"crossref","first-page":"e33418","DOI":"10.1371\/journal.pone.0033418","article-title":"Targeting the lactate transporter MCT1 in endothelial cells inhibits lactate-induced HIF-1 activation and tumor angiogenesis","volume":"7","author":"Sonveaux","year":"2012","journal-title":"PLoS One"},{"issue":"48","key":"2025070311221658800_bib48","doi-asserted-by":"crossref","first-page":"18154","DOI":"10.1073\/pnas.0602235103","article-title":"Prolyl hydroxylase-1 negatively regulates IkappaB kinase-beta, giving insight into hypoxia-induced NFkappaB activity","volume":"103","author":"Cummins","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"2025070311221658800_bib49","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1158\/0008-5472.CAN-10-2828","article-title":"Lactate influx through the endothelial cell monocarboxylate transporter MCT1 supports an NF-\u03baB\/IL-8 pathway that drives tumor angiogenesis","volume":"71","author":"V\u00e9gran","year":"2011","journal-title":"Cancer Res"},{"issue":"4","key":"2025070311221658800_bib50","doi-asserted-by":"crossref","first-page":"e61991","DOI":"10.1371\/journal.pone.0061991","article-title":"Acidosis activation of the proton-sensing GPR4 receptor stimulates vascular endothelial cell inflammatory responses revealed by transcriptome analysis","volume":"8","author":"Dong","year":"2013","journal-title":"PLoS One"},{"issue":"11","key":"2025070311221658800_bib51","doi-asserted-by":"crossref","first-page":"e27586","DOI":"10.1371\/journal.pone.0027586","article-title":"Activation of GPR4 by acidosis increases endothelial cell adhesion through the cAMP\/Epac pathway","volume":"6","author":"Chen","year":"2011","journal-title":"PLoS One"},{"issue":"2","key":"2025070311221658800_bib52","doi-asserted-by":"crossref","first-page":"100848","DOI":"10.1016\/j.isci.2020.100848","article-title":"The proton-sensing GPR4 receptor regulates paracellular gap formation and permeability of vascular endothelial cells","volume":"23","author":"Krewson","year":"2020","journal-title":"iScience"},{"issue":"12","key":"2025070311221658800_bib53","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.1002\/iub.2151","article-title":"Activation of GPR81 by lactate inhibits oscillatory shear stress-induced endothelial inflammation by activating the expression of KLF2","volume":"71","author":"Sun","year":"2019","journal-title":"IUBMB Life"},{"issue":"1","key":"2025070311221658800_bib54","doi-asserted-by":"crossref","first-page":"4280","DOI":"10.1038\/s41467-023-40021-6","article-title":"The metabolic function of pyruvate kinase M2 regulates reactive oxygen species production and microbial killing by neutrophils","volume":"14","author":"Toller-Kawahisa","year":"2023","journal-title":"Nat Commun"},{"issue":"2","key":"2025070311221658800_bib55","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/0006-291X(85)91157-X","article-title":"Pancreatic islets synthesize phospholipids de novo from glucose via acyl-dihydroxyacetone phosphate","volume":"132","author":"Dunlop","year":"1985","journal-title":"Biochem Biophys Res Commun"},{"issue":"3","key":"2025070311221658800_bib56","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1042\/bj1220285","article-title":"Dihydroxyacetone phosphate. Its structure and reactivity with -glycerophosphate dehydrogenase, aldolase and triose phosphate isomerase and some possible metabolic implications","volume":"122","author":"Reynolds","year":"1971","journal-title":"Biochem J"},{"issue":"3","key":"2025070311221658800_bib57","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/s42255-022-00550-8","article-title":"Switching to the cyclic pentose phosphate pathway powers the oxidative burst in activated neutrophils","volume":"4","author":"Britt","year":"2022","journal-title":"Nat Metab"},{"issue":"3","key":"2025070311221658800_bib58","doi-asserted-by":"crossref","first-page":"465","DOI":"10.18388\/abp.2015_1055","article-title":"Selected mucolytic, anti-inflammatory and cardiovascular drugs change the ability of neutrophils to form extracellular traps (NETs)","volume":"62","author":"Zawrotniak","year":"2015","journal-title":"Acta Biochim Pol"},{"issue":"17","key":"2025070311221658800_bib59","doi-asserted-by":"crossref","first-page":"4480","DOI":"10.1016\/j.cell.2021.07.004","article-title":"Selective activation of PFKL suppresses the phagocytic oxidative burst","volume":"184","author":"Amara","year":"2021","journal-title":"Cell"},{"issue":"2","key":"2025070311221658800_bib60","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/imm.12437","article-title":"Metabolic requirements for neutrophil extracellular traps formation","volume":"145","author":"Rodr\u00edguez-Espinosa","year":"2015","journal-title":"Immunology"},{"issue":"36","key":"2025070311221658800_bib61","doi-asserted-by":"crossref","first-page":"22174","DOI":"10.1074\/jbc.M115.640094","article-title":"A metabolic shift toward pentose phosphate pathway is necessary for amyloid fibril- and phorbol 12-myristate 13-acetate-induced neutrophil extracellular trap (NET) formation","volume":"290","author":"Azevedo","year":"2015","journal-title":"J Biol Chem"},{"key":"2025070311221658800_bib62","doi-asserted-by":"crossref","first-page":"849136","DOI":"10.1155\/2012\/849136","article-title":"The impact of various reactive oxygen species on the formation of neutrophil extracellular traps","volume":"2012","author":"Kirchner","year":"2012","journal-title":"Mediators Inflamm"},{"issue":"8","key":"2025070311221658800_bib63","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1182\/blood.2021012322","article-title":"PKM2 promotes neutrophil activation and cerebral thromboinflammation: therapeutic implications for ischemic stroke","volume":"139","author":"Dhanesha","year":"2022","journal-title":"Blood"},{"issue":"4","key":"2025070311221658800_bib64","doi-asserted-by":"crossref","first-page":"763","DOI":"10.4049\/jimmunol.1901086","article-title":"Pyruvate kinase M2 promotes expression of proinflammatory mediators in house dust mite-induced allergic airways disease","volume":"204","author":"van de Wetering","year":"2020","journal-title":"J Immunol"},{"issue":"7","key":"2025070311221658800_bib65","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1016\/j.cellsig.2015.02.032","article-title":"Pyruvate kinase M2 accelerates pro-inflammatory cytokine secretion and cell proliferation induced by lipopolysaccharide in colorectal cancer","volume":"27","author":"Yang","year":"2015","journal-title":"Cell Signal"},{"issue":"4","key":"2025070311221658800_bib66","doi-asserted-by":"crossref","first-page":"806","DOI":"10.3324\/haematol.2018.205724","article-title":"Aerobic glycolysis fuels platelet activation: small-molecule modulators of platelet metabolism as anti-thrombotic agents","volume":"104","author":"Kulkarni","year":"2019","journal-title":"Haematologica"},{"issue":"2","key":"2025070311221658800_bib67","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1083\/jcb.138.2.323","article-title":"Thrombin stimulates glucose transport in human platelets via the translocation of the glucose transporter GLUT-3 from alpha-granules to the cell surface","volume":"138","author":"Heijnen","year":"1997","journal-title":"J Cell Biol"},{"issue":"6","key":"2025070311221658800_bib68","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.3892\/ol.2012.928","article-title":"Energy metabolism of cancer: glycolysis versus oxidative phosphorylation (review)","volume":"4","author":"Zheng","year":"2012","journal-title":"Oncol Lett"},{"issue":"12","key":"2025070311221658800_bib69","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1182\/blood.2020007140","article-title":"The metabolic enzyme pyruvate kinase M2 regulates platelet function and arterial thrombosis","volume":"137","author":"Nayak","year":"2021","journal-title":"Blood"},{"issue":"1","key":"2025070311221658800_bib70","doi-asserted-by":"crossref","first-page":"37727","DOI":"10.1038\/srep37727","article-title":"The Warburg effect mediator pyruvate kinase M2 expression and regulation in the retina","volume":"6","author":"Rajala","year":"2016","journal-title":"Sci Rep"},{"issue":"15","key":"2025070311221658800_bib71","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1093\/cvr\/cvad149","article-title":"Metabolic targeting of platelets to combat thrombosis: dawn of a new paradigm?","volume":"119","author":"Flora","year":"2023","journal-title":"Cardiovasc Res"},{"issue":"suppl 1","key":"2025070311221658800_bib72","article-title":"Pyruvate kinase M2 regulates SNAP23-mediated platelet granule exocytosis, neutrophil extracellular traps formation and experimental venous thrombosis [abstract]","volume":"44","author":"Nayak","year":"2024","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2025070311221658800_bib73","doi-asserted-by":"crossref","first-page":"1009952","DOI":"10.3389\/fphar.2022.1009952","article-title":"Small extracellular vesicles in metabolic remodeling of tumor cells: cargos and translational application","volume":"13","author":"Yang","year":"2022","journal-title":"Front Pharmacol"},{"issue":"15","key":"2025070311221658800_bib74","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1182\/bloodadvances.2018022392","article-title":"Dichloroacetate, an inhibitor of pyruvate dehydrogenase kinases, inhibits platelet aggregation and arterial thrombosis","volume":"2","author":"Nayak","year":"2018","journal-title":"Blood Adv"},{"issue":"1","key":"2025070311221658800_bib75","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1743-7075-11-10","article-title":"The pivotal role of pyruvate dehydrogenase kinases in metabolic flexibility","volume":"11","author":"Zhang","year":"2014","journal-title":"Nutr Metab"},{"issue":"11","key":"2025070311221658800_bib76","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1182\/bloodadvances.2023010100","article-title":"Mitochondrial pyruvate dehydrogenase kinases contribute to platelet function and thrombosis in mice by regulating aerobic glycolysis","volume":"7","author":"Flora","year":"2023","journal-title":"Blood Adv"},{"issue":"13","key":"2025070311221658800_bib77","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.3390\/cells12131802","article-title":"Platelet metabolic flexibility: a matter of substrate and location","volume":"12","author":"Ravera","year":"2023","journal-title":"Cells"},{"key":"2025070311221658800_bib78","doi-asserted-by":"crossref","first-page":"155596","DOI":"10.1016\/j.metabol.2023.155596","article-title":"Energy metabolism in platelets fuels thrombus formation: Halting the thrombosis engine with small-molecule modulators of platelet metabolism","volume":"145","author":"Kulkarni","year":"2023","journal-title":"Metabolism"},{"issue":"1","key":"2025070311221658800_bib79","doi-asserted-by":"crossref","first-page":"4829","DOI":"10.1038\/s41467-023-40600-7","article-title":"MTH1 protects platelet mitochondria from oxidative damage and regulates platelet function and thrombosis","volume":"14","author":"Ding","year":"2023","journal-title":"Nat Commun"},{"issue":"5","key":"2025070311221658800_bib80","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/j.cmet.2016.04.001","article-title":"Mapping the human platelet lipidome reveals cytosolic phospholipase A2 as a regulator of mitochondrial bioenergetics during activation","volume":"23","author":"Slatter","year":"2016","journal-title":"Cell Metab"},{"issue":"1","key":"2025070311221658800_bib81","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1172\/JCI105964","article-title":"Lipid metabolism in human platelets. I. Evidence for a complete fatty acid synthesizing system","volume":"48","author":"Majerus","year":"1969","journal-title":"J Clin Invest"},{"issue":"2","key":"2025070311221658800_bib82","doi-asserted-by":"crossref","first-page":"e22768","DOI":"10.1096\/fj.202201321RR","article-title":"Fatty acid oxidation fuels agonist-induced platelet activation and thrombus formation: targeting \u03b2-oxidation of fatty acids as an effective anti-platelet strategy","volume":"37","author":"Kulkarni","year":"2023","journal-title":"FASEB J"},{"issue":"suppl 1","key":"2025070311221658800_bib83","article-title":"The glycolytic enzyme pyruvate kinase M2 regulates deep vein thrombosis [abstract]","volume":"146","author":"Nayak","year":"2022","journal-title":"Circulation"},{"issue":"15","key":"2025070311221658800_bib84","doi-asserted-by":"crossref","first-page":"3906","DOI":"10.1182\/bloodadvances.2024013199","article-title":"Deletion of pyruvate dehydrogenase kinases reduces susceptibility to deep vein thrombosis in mice","volume":"8","author":"Flora","year":"2024","journal-title":"Blood Adv"},{"issue":"12","key":"2025070311221658800_bib85","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1161\/CIRCULATIONAHA.112.000966","article-title":"Hydrogen peroxide promotes aging-related platelet hyperactivation and thrombosis","volume":"127","author":"Dayal","year":"2013","journal-title":"Circulation"},{"issue":"4","key":"2025070311221658800_bib86","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1182\/blood-2017-01-764910","article-title":"Platelet amyloid precursor protein is a modulator of venous thromboembolism in mice","volume":"130","author":"Canobbio","year":"2017","journal-title":"Blood"},{"issue":"6","key":"2025070311221658800_bib87","doi-asserted-by":"crossref","first-page":"161","DOI":"10.14740\/jem848","article-title":"Protective effect of metformin on venous thrombosis in diabetic patients: findings from a systematic review","volume":"12","author":"Alqahtani","year":"2022","journal-title":"J Endocrinol Metab"},{"issue":"1","key":"2025070311221658800_bib88","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1042\/BST20200611","article-title":"Endothelial response to glucose: dysfunction, metabolism, and transport","volume":"49","author":"Clyne","year":"2021","journal-title":"Biochem Soc Trans"},{"issue":"5","key":"2025070311221658800_bib89","doi-asserted-by":"crossref","first-page":"932","DOI":"10.2337\/db18-0981","article-title":"Glucose metabolism is required for platelet hyperactivation in a murine model of type 1 diabetes","volume":"68","author":"Fidler","year":"2019","journal-title":"Diabetes"},{"issue":"4","key":"2025070311221658800_bib90","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1007\/s13577-023-00905-7","article-title":"Neutrophil (dys)function due to altered immuno-metabolic axis in type 2 diabetes: implications in combating infections","volume":"36","author":"Thimmappa","year":"2023","journal-title":"Hum Cell"},{"issue":"4","key":"2025070311221658800_bib91","doi-asserted-by":"crossref","first-page":"3169","DOI":"10.3390\/ijms24043169","article-title":"A comprehensive review of risk factors for venous thromboembolism: from epidemiology to pathophysiology","volume":"24","author":"Pastori","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2025070311221658800_bib92","doi-asserted-by":"crossref","first-page":"944506","DOI":"10.3389\/fcvm.2022.944506","article-title":"Hyperglycemia may increase deep vein thrombosis in trauma patients with lower limb fracture","volume":"9","author":"Liu","year":"2022","journal-title":"Front Cardiovasc Med"},{"issue":"1","key":"2025070311221658800_bib93","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1186\/s12891-022-05862-0","article-title":"Association between hyperglycemia on admission and preoperative deep venous thrombosis in patients with femoral neck fractures","volume":"23","author":"Yao","year":"2022","journal-title":"BMC Musculoskelet Disord"},{"issue":"8","key":"2025070311221658800_bib94","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/s41574-023-00833-4","article-title":"Metformin: update on mechanisms of action and repurposing potential","volume":"19","author":"Foretz","year":"2023","journal-title":"Nat Rev Endocrinol"},{"issue":"7","key":"2025070311221658800_bib95","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1016\/j.jtha.2023.03.014","article-title":"Overexpression of facilitative glucose transporter-3 and membrane procoagulation in maternal platelets of preeclamptic pregnancy","volume":"21","author":"Agbani","year":"2023","journal-title":"J Thromb Haemost"},{"issue":"1","key":"2025070311221658800_bib96","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1186\/s12943-024-02119-3","article-title":"Altered metabolism in cancer: insights into energy pathways and therapeutic targets","volume":"23","author":"Tufail","year":"2024","journal-title":"Mol Cancer"},{"key":"2025070311221658800_bib97","doi-asserted-by":"crossref","first-page":"757323","DOI":"10.3389\/fonc.2021.757323","article-title":"Alternative energy: breaking down the diverse metabolic features of lung cancers","volume":"11","author":"Cargill","year":"2021","journal-title":"Front Oncol"},{"issue":"6","key":"2025070311221658800_bib98","doi-asserted-by":"crossref","first-page":"5564","DOI":"10.3390\/ijms24065564","article-title":"Promising strategy of mPTP modulation in cancer therapy: an emerging progress and future insight","volume":"24","author":"Waseem","year":"2023","journal-title":"Int J Mol Sci"},{"issue":"11","key":"2025070311221658800_bib99","doi-asserted-by":"crossref","first-page":"e791","DOI":"10.1002\/mco2.791","article-title":"Inducing disulfidptosis in tumors:potential pathways and significance","volume":"5","author":"Mi","year":"2024","journal-title":"MedComm (2020)"},{"issue":"15","key":"2025070311221658800_bib100","doi-asserted-by":"crossref","first-page":"e169893","DOI":"10.1172\/JCI169893","article-title":"Neutrophil glucose flux as a therapeutic target in antiphospholipid syndrome","volume":"134","author":"Tambralli","year":"2024","journal-title":"J Clin Invest"},{"issue":"1","key":"2025070311221658800_bib101","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/imm.13871","article-title":"Metabolic reprogramming in cancer: implications for immunosuppressive microenvironment","volume":"174","author":"Aden","year":"2025","journal-title":"Immunology"},{"issue":"2","key":"2025070311221658800_bib102","doi-asserted-by":"crossref","first-page":"e30462","DOI":"10.1371\/journal.pone.0030462","article-title":"Clotrimazole preferentially inhibits human breast cancer cell proliferation, viability and glycolysis","volume":"7","author":"Furtado","year":"2012","journal-title":"PLoS One"},{"issue":"8","key":"2025070311221658800_bib103","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.7150\/ijbs.59855","article-title":"Specific pyruvate kinase M2 inhibitor, compound 3K, induces autophagic cell death through disruption of the glycolysis pathway in ovarian cancer cells","volume":"17","author":"Park","year":"2021","journal-title":"Int J Biol Sci"},{"issue":"40","key":"2025070311221658800_bib104","doi-asserted-by":"crossref","first-page":"e2123231119","DOI":"10.1073\/pnas.2123231119","article-title":"Dual roles of \u03b2-arrestin 1 in mediating cell metabolism and proliferation in gastric cancer","volume":"119","author":"Yu","year":"2022","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025070311221658800_bib105","doi-asserted-by":"crossref","first-page":"112686","DOI":"10.1016\/j.biopha.2022.112686","article-title":"Oxamate targeting aggressive cancers with special emphasis to brain tumors","volume":"147","author":"Altinoz","year":"2022","journal-title":"Biomed Pharmacother"},{"issue":"4","key":"2025070311221658800_bib106","doi-asserted-by":"crossref","first-page":"BSR20204402","DOI":"10.1042\/BSR20204402","article-title":"Pyruvate dehydrogenase kinases (PDKs): an overview toward clinical applications","volume":"41","author":"Wang","year":"2021","journal-title":"Biosci Rep"},{"issue":"1","key":"2025070311221658800_bib107","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.molmed.2019.06.009","article-title":"The mitochondrion as an emerging therapeutic target in cancer","volume":"26","author":"Roth","year":"2020","journal-title":"Trends Mol Med"},{"issue":"2","key":"2025070311221658800_bib108","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1161\/ATVBAHA.120.315565","article-title":"NADPH oxidases are required for full platelet activation in vitro and thrombosis in vivo but dispensable for plasma coagulation and hemostasis","volume":"41","author":"Vara","year":"2021","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"7","key":"2025070311221658800_bib109","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1111\/liv.15596","article-title":"Setanaxib, a first-in-class selective NADPH oxidase 1\/4 inhibitor for primary biliary cholangitis: a randomized, placebo-controlled, phase 2 trial","volume":"43","author":"Invernizzi","year":"2023","journal-title":"Liver Int"},{"key":"2025070311221658800_bib110","doi-asserted-by":"crossref","first-page":"670076","DOI":"10.3389\/fphar.2021.670076","article-title":"Coordinated contribution of NADPH oxidase- and mitochondria-derived reactive oxygen species in metabolic syndrome and its implication in renal dysfunction","volume":"12","author":"Lee","year":"2021","journal-title":"Front Pharmacol"},{"issue":"7","key":"2025070311221658800_bib111","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/j.joca.2024.02.948","article-title":"The efficacy and safety of a fixed-dose combination of apocynin and paeonol, APPA, in symptomatic knee OA: a double-blind, randomized, placebo-controlled, clinical trial","volume":"32","author":"Bihlet","year":"2024","journal-title":"Osteoarthritis Cartilage"},{"key":"2025070311221658800_bib112","doi-asserted-by":"crossref","first-page":"100037","DOI":"10.1016\/j.arres.2022.100037","article-title":"Pharmacological significance of MitoQ in ameliorating mitochondria-related diseases","volume":"5","author":"Sulaimon","year":"2022","journal-title":"Adv Redox Res"},{"issue":"12","key":"2025070311221658800_bib113","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.3390\/antiox13121444","article-title":"MnSOD mimetics in therapy: exploring their role in combating oxidative stress-related diseases","volume":"13","author":"Grujicic","year":"2024","journal-title":"Antioxidants (Basel)"},{"issue":"12","key":"2025070311221658800_bib114","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.3390\/biom14121507","article-title":"Decoding the nexus: cellular and molecular mechanisms linking stroke and neurotoxic microenvironments in brain cancer patients","volume":"14","author":"Menounos","year":"2024","journal-title":"Biomolecules"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/146\/1\/29\/2383728\/blood_bld-2024-027636-main.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/146\/1\/29\/2383728\/blood_bld-2024-027636-main.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T15:22:36Z","timestamp":1751556156000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/146\/1\/29\/536308\/Metabolic-pathways-in-deep-vein-thrombosis-a-new"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,3]]},"references-count":114,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,7,3]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2024027636","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,7,3]]},"published":{"date-parts":[[2025,7,3]]}}}