{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:05:52Z","timestamp":1772136352928,"version":"3.50.1"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"the Anhui Provincial Health Commission (Health Research Program of Anhui\uff09","award":["AHWJ2023BAc20016"],"award-info":[{"award-number":["AHWJ2023BAc20016"]}]},{"name":"the Anhui Provincial Health Commission (Health Research Program of Anhui\uff09","award":["AHWJ2023BAa20021"],"award-info":[{"award-number":["AHWJ2023BAa20021"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    While fructose-1,6-diphosphate (FDP) has been clinically applied in ischemic conditions, its comprehensive effects on hemostasis remain to be fully elucidated. This in vitro study examined the influence of FDP on coagulation and platelet function using thromboelastography (TEG) across three platforms, coagulation factor assays, and platelet aggregation tests over a concentration range of 0\u20136\u00a0mg\/mL. The results revealed that FDP concentration-dependently prolonged TEG R-time (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.01), with an increase of 21.8\u201348.3% at the clinically relevant concentration of 3.71\u00a0mg\/mL. Strong inverse correlations were observed between FDP concentration and the activities of factors V, VII, IX, XI, and XII (\n                    <jats:italic>r\u2009<\/jats:italic>\n                    = \u2212\u20090.989 to\u2009\u2212\u20090.997,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001), whereas factors II, VIII, and X remained unaltered. Furthermore, FDP significantly inhibited platelet aggregation (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001), nearly abolishing epinephrine- and ADP-induced aggregation at 6\u00a0mg\/mL under unbuffered conditions. pH-control experiments confirmed that the anticoagulant effects were FDP-specific, while the antiplatelet effects were primarily mediated by FDP with a partial pH-dependent component. These findings demonstrate that FDP possesses dual anticoagulant and antiplatelet properties through selective inhibition of coagulation initiation factors and broad suppression of platelet responsiveness, suggesting potential implications for clinical use in high-risk populations and warranting further investigation.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-30815-7","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T04:45:29Z","timestamp":1767588329000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual anticoagulant and antiplatelet effects of fructose-1,6-diphosphate in vitro"],"prefix":"10.1038","volume":"16","author":[{"given":"Yalong","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingguo","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tongqing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"30815_CR1","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/nature23275","volume":"548","author":"CS Zhang","year":"2017","unstructured":"Zhang, C. S. et al. Fructose-1,6-bisphosphate and aldolase mediate glucose sensing by AMPK. Nature 548, 112\u2013116 (2017).","journal-title":"Nature"},{"key":"30815_CR2","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1515\/acph-2015-0020","volume":"65","author":"TT Li","year":"2015","unstructured":"Li, T. T., Xie, J. Z., Wang, L., Gao, Y. Y. & Jiang, X. H. Rational application of fructose-1,6-diphosphate: from the perspective of pharmacokinetics. Acta Pharmacol Sin 65, 147\u2013157 (2015).","journal-title":"Acta Pharmacol Sin"},{"key":"30815_CR3","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1002\/j.1875-9114.1994.tb02849.x","volume":"14","author":"MA Munger","year":"1994","unstructured":"Munger, M. A., Botti, R. E., Grinblatt, M. A. & Kasmer, R. J. Effect of intravenous fructose-1,6-diphosphate on myocardial contractility in patients with left ventricular dysfunction. Pharmacotherapy 14, 522\u2013528 (1994).","journal-title":"Pharmacotherapy"},{"key":"30815_CR4","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1053\/meta.2000.6249","volume":"49","author":"AK Markov","year":"2000","unstructured":"Markov, A. K. et al. Metabolic responses to fructose-1,6-diphosphate in healthy subjects. Metabolism 49, 698\u2013703 (2000).","journal-title":"Metabolism"},{"key":"30815_CR5","first-page":"249","volume":"5","author":"P Ripari","year":"1988","unstructured":"Ripari, P. & Pieralisi, G. Effects of fructose-1,6-diphosphate on heart rate, ventilation, oxygen consumption and endurance performance. Pharmatherapeutica 5, 249\u2013255 (1988).","journal-title":"Pharmatherapeutica"},{"key":"30815_CR6","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1016\/0006-2952(92)90212-2","volume":"43","author":"L Cavallini","year":"1992","unstructured":"Cavallini, L., Deana, R., Francesconi, M. A. & Alexandre, A. Fructose-1,6-diphosphate inhibits platelet activation. Biochem. Pharmacol. 43, 1539\u20131544 (1992).","journal-title":"Biochem. Pharmacol."},{"key":"30815_CR7","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1007\/s11239-009-0387-2","volume":"29","author":"LM de Oliveira","year":"2010","unstructured":"de Oliveira, L. M. et al. Fructose-1,6-bisphosphate inhibits in vitro and ex vivo platelet aggregation induced by ADP and ameliorates coagulation alterations in experimental sepsis in rats. J. Thromb. Thrombolysis 29, 387\u2013394 (2010).","journal-title":"J. Thromb. Thrombolysis"},{"key":"30815_CR8","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1038\/s41598-021-04263-y","volume":"12","author":"TQ Chen","year":"2022","unstructured":"Chen, T. Q. et al. The effects of fructose diphosphate on routine coagulation tests in vitro. Sci. Rep. 12, 304 (2022).","journal-title":"Sci. Rep."},{"key":"30815_CR9","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1002\/ajh.23599","volume":"89","author":"D Whiting","year":"2014","unstructured":"Whiting, D. & DiNardo, J. A. TEG and ROTEM: technology and clinical applications. Am. J. Hematol. 89, 228\u2013232 (2014).","journal-title":"Am. J. Hematol."},{"key":"30815_CR10","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1002\/rth2.12140","volume":"2","author":"S Platton","year":"2018","unstructured":"Platton, S. et al. A multicenter study to evaluate automated platelet aggregometry on Sysmex CS-series coagulation analyzers\u2014preliminary findings. Res. Pract. Thromb. Haemost. 2, 778\u2013789 (2018).","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"30815_CR11","first-page":"1","volume":"28","author":"DJ Christie","year":"2008","unstructured":"Christie, D. J. et al. Platelet function testing by aggregometry; approved guideline: document H58-A. Clin. Lab Stand. Inst. 28, 1\u201360 (2008).","journal-title":"Clin. Lab Stand. Inst."},{"key":"30815_CR12","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1111\/j.1365-2141.2011.08793.x","volume":"155","author":"P Harrison","year":"2011","unstructured":"Harrison, P. et al. Guidelines for the laboratory investigation of heritable disorders of platelet function. Br. J. Haematol. 155, 30\u201344 (2011).","journal-title":"Br. J. Haematol."},{"key":"30815_CR13","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1111\/jth.12231","volume":"11","author":"M Cattaneo","year":"2013","unstructured":"Cattaneo, M. et al. Recommendations for the standardization of light transmission aggregometry: a consensus of the working party from the platelet physiology subcommittee of SSC\/ISTH. J. Thromb. Haemost. 11, 1183\u20131189 (2013).","journal-title":"J. Thromb. Haemost."},{"key":"30815_CR14","doi-asserted-by":"publisher","first-page":"10363","DOI":"10.1021\/bi00107a001","volume":"30","author":"EW Davie","year":"1991","unstructured":"Davie, E. W., Fujikawa, K. & Kisiel, W. The coagulation cascade: initiation, maintenance, and regulation. Biochemistry 30, 10363\u201310370 (1991).","journal-title":"Biochemistry"},{"key":"30815_CR15","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.bcmd.2005.12.034","volume":"36","author":"KG Mann","year":"2006","unstructured":"Mann, K. G., Brummel-Ziedins, K., Orfeo, T. & Butenas, S. Models of blood coagulation. Blood Cells Mol. Dis. 36, 108\u2013117 (2006).","journal-title":"Blood Cells Mol. Dis."},{"key":"30815_CR16","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1093\/labmed\/lmx050","volume":"48","author":"WE Winter","year":"2017","unstructured":"Winter, W. E., Flax, S. D. & Harris, N. S. Coagulation testing in the core laboratory. Lab. Med. 48, 295\u2013313 (2017).","journal-title":"Lab. Med."},{"key":"30815_CR17","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1055\/s-0037-1619637","volume":"24","author":"J Harenberg","year":"2004","unstructured":"Harenberg, J. & Fenyvesi, T. Heparin, thrombin and Factor Xa inhibitors. Hamostaseologie 24, 261\u2013278 (2004).","journal-title":"Hamostaseologie"},{"key":"30815_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/bs.pmbts.2019.02.002","volume":"163","author":"C Hao","year":"2019","unstructured":"Hao, C., Xu, H., Yu, L. & Zhang, L. Heparin: an essential drug for modern medicine. Prog. Mol. Biol. Transl. Sci. 163, 1\u201319 (2019).","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"30815_CR19","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1080\/07391102.2011.10507389","volume":"29","author":"P Singh","year":"2011","unstructured":"Singh, P., Singh, K. & Jairajpuri, M. A. Energetics of hydrogen bond switch, residue burial and cavity analysis reveals molecular basis of improved heparin binding to antithrombin. J. Biomol. Struct. Dyn. 29, 339\u2013350 (2011).","journal-title":"J. Biomol. Struct. Dyn."},{"key":"30815_CR20","first-page":"148","volume":"21","author":"K Nakamura","year":"1994","unstructured":"Nakamura, K. et al. Anticoagulant effects of warfarin and kinetics of K vitamins in blood and feces. Artery 21, 148\u2013160 (1994).","journal-title":"Artery"},{"key":"30815_CR21","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1161\/01.HYP.31.2.603","volume":"31","author":"A Spalding","year":"1998","unstructured":"Spalding, A. et al. Mechanism of epinephrine-induced platelet aggregation. Hypertension 31, 603\u2013607 (1998).","journal-title":"Hypertension"},{"key":"30815_CR22","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.pharmthera.2013.08.005","volume":"141","author":"CN Floyd","year":"2014","unstructured":"Floyd, C. N. & Ferro, A. Mechanisms of aspirin resistance. Pharmacol. Ther. 141, 69\u201378 (2014).","journal-title":"Pharmacol. Ther."},{"key":"30815_CR23","doi-asserted-by":"publisher","first-page":"3087","DOI":"10.1182\/blood.2021013614","volume":"139","author":"LJ Feitsma","year":"2022","unstructured":"Feitsma, L. J. et al. Structural insights into collagen binding by platelet receptor glycoprotein VI. Blood 139, 3087\u20133098 (2022).","journal-title":"Blood"},{"key":"30815_CR24","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1002\/jcp.10222","volume":"194","author":"KC Lai","year":"2003","unstructured":"Lai, K. C. & Flaumenhaft, R. SNARE protein degradation upon platelet activation: calpain cleaves SNAP-23. J. Cell. Physiol. 194, 206\u2013214 (2003).","journal-title":"J. Cell. Physiol."},{"key":"30815_CR25","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1159\/000175993","volume":"83","author":"SA Mousa","year":"1993","unstructured":"Mousa, S. A., Forsythe, M. S., Bozarth, J. M. & Reilly, T. M. Effect of single oral dose of aspirin on human platelet functions and plasma plasminogen activator inhibitor-1. Cardiology 83, 367\u2013373 (1993).","journal-title":"Cardiology"},{"key":"30815_CR26","doi-asserted-by":"publisher","first-page":"745","DOI":"10.2165\/00003495-199754050-00006","volume":"54","author":"AJ Coukell","year":"1997","unstructured":"Coukell, A. J. & Markham, A. Clopidogrel. Drugs 54, 745\u2013750 (1997).","journal-title":"Drugs"},{"key":"30815_CR27","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1016\/j.jacbts.2021.09.010","volume":"6","author":"Y Ito","year":"2021","unstructured":"Ito, Y. et al. Rivaroxaban, a direct oral Factor Xa inhibitor, attenuates atherosclerosis by alleviating Factor Xa-PAR2-mediated autophagy suppression. JACC Basic Transl. Sci. 6, 964\u2013980 (2021).","journal-title":"JACC Basic Transl. Sci."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-30815-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-30815-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-30815-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T21:08:00Z","timestamp":1768165680000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-30815-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,5]]},"references-count":27,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["30815"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-30815-7","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-7406959\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,5]]},"assertion":[{"value":"19 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All procedures involving human participants were in accordance with the ethical standards of the institutional research committee and the 1964 Helsinki Declaration and its later amendments. The study was approved by the Ethics Review Committee of Anhui No. 2 Provincial People\u2019s Hospital (Approval [R] 2024\u2013037).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics statement"}},{"value":"Informed consent was obtained from all subjects involved in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}],"article-number":"1163"}}