{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:46:24Z","timestamp":1790138784192,"version":"4.0.1"},"reference-count":34,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["16K11119"],"award-info":[{"award-number":["16K11119"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Placenta"],"published-print":{"date-parts":[[2018,5]]},"DOI":"10.1016\/j.placenta.2018.03.006","type":"journal-article","created":{"date-parts":[[2018,3,25]],"date-time":"2018-03-25T23:17:28Z","timestamp":1522019848000},"page":"1-6","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":16,"special_numbering":"C","title":["Recombinant human soluble thrombomodulin as an anticoagulation therapy improves recurrent miscarriage and fetal growth restriction due to placental insufficiency \u2013 The leading cause of preeclampsia"],"prefix":"10.1016","volume":"65","author":[{"given":"Takumi","family":"Sano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5581-8518","authenticated-orcid":false,"given":"Yoshito","family":"Terai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Daimon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misa","family":"Nunode","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Nagayasu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuko","family":"Okamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Fujita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masami","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahide","family":"Ohmichi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"5","key":"10.1016\/j.placenta.2018.03.006_bib1","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.fertnstert.2012.06.048","article-title":"Evaluation and treatment of recurrent pregnancy loss: a committee opinion","volume":"98","year":"2012","journal-title":"Fertil. Steril."},{"issue":"1","key":"10.1016\/j.placenta.2018.03.006_bib2","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1093\/humrep\/16.1.102","article-title":"Obstetric and neonatal outcome in women with a history of recurrent miscarriage: a cohort study","volume":"16","author":"Jivraj","year":"2001","journal-title":"Hum. Reprod. (Oxford, England)"},{"issue":"6","key":"10.1016\/j.placenta.2018.03.006_bib3","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1093\/humupd\/dmt019","article-title":"Antithrombotic therapy for pregnancy loss","volume":"19","author":"de Jong","year":"2013","journal-title":"Hum. Reprod. Update"},{"issue":"Suppl 1","key":"10.1016\/j.placenta.2018.03.006_bib4","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/S0301-2115(03)00168-4","article-title":"Angiogenesis and vasculogenesis in pregnancy","volume":"110","author":"Zygmunt","year":"2003","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"issue":"5419","key":"10.1016\/j.placenta.2018.03.006_bib5","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1126\/science.284.5419.1534","article-title":"Defective angiogenesis in mice lacking endoglin","volume":"284","author":"Li","year":"1999","journal-title":"Science (New York, NY)"},{"issue":"4","key":"10.1016\/j.placenta.2018.03.006_bib6","doi-asserted-by":"crossref","first-page":"278","DOI":"10.5483\/BMBRep.2008.41.4.278","article-title":"Vascular endothelial growth factor-dependent and -independent regulation of angiogenesis","volume":"41","author":"Shibuya","year":"2008","journal-title":"BMB Rep."},{"issue":"5","key":"10.1016\/j.placenta.2018.03.006_bib7","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1172\/JCI17189","article-title":"Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia","volume":"111","author":"Maynard","year":"2003","journal-title":"J.\u00a0Clin. Invest."},{"issue":"6","key":"10.1016\/j.placenta.2018.03.006_bib8","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1111\/j.1600-0897.2004.00237.x","article-title":"Ecology of danger-dependent cytokine-boosted spontaneous abortion in the CBA x DBA\/2 mouse model. I. Synergistic effect of LPS and (TNF-alpha\u202f+\u202fIFN-gamma) on pregnancy loss","volume":"52","author":"Clark","year":"2004","journal-title":"Am. J. Rep. Immun. (New York, NY: 1989)"},{"issue":"6","key":"10.1016\/j.placenta.2018.03.006_bib9","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1111\/j.1600-0897.2008.00652.x","article-title":"Ecology of danger-dependent cytokine-boosted spontaneous abortion in the CBA x DBA\/2 mouse model: II. Fecal LPS levels in colonies with different basal abortion rates","volume":"60","author":"Clark","year":"2008","journal-title":"Am. J. Rep. Immun. (New York, NY: 1989)"},{"issue":"17","key":"10.1016\/j.placenta.2018.03.006_bib10","doi-asserted-by":"crossref","first-page":"4101","DOI":"10.1182\/blood-2008-12-194258","article-title":"Pravastatin prevents miscarriages in mice: role of tissue factor in placental and fetal injury","volume":"113","author":"Redecha","year":"2009","journal-title":"Blood"},{"issue":"2","key":"10.1016\/j.placenta.2018.03.006_bib11","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/j.1600-0897.2008.00605.x","article-title":"LPS-induced murine abortions require C5 but not C3, and are prevented by upregulating expression of the CD200 tolerance signaling molecule","volume":"60","author":"Yu","year":"2008","journal-title":"Am. J. Rep. Immun. (New York, NY: 1989)"},{"issue":"10","key":"10.1016\/j.placenta.2018.03.006_bib12","doi-asserted-by":"crossref","first-page":"e13663","DOI":"10.1371\/journal.pone.0013663","article-title":"A\u00a0new mouse model to explore therapies for preeclampsia","volume":"5","author":"Ahmed","year":"2010","journal-title":"PLoS One"},{"key":"10.1016\/j.placenta.2018.03.006_bib13","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/1423-0127-19-34","article-title":"The role of thrombomodulin lectin-like domain in inflammation","volume":"19","author":"Li","year":"2012","journal-title":"J.\u00a0Biomed. Sci."},{"issue":"3","key":"10.1016\/j.placenta.2018.03.006_bib14","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1182\/blood-2007-09-111302","article-title":"Maternal Par4 and platelets contribute to defective placenta formation in mouse embryos lacking thrombomodulin","volume":"112","author":"Sood","year":"2008","journal-title":"Blood"},{"issue":"4","key":"10.1016\/j.placenta.2018.03.006_bib15","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1161\/ATVBAHA.115.306780","article-title":"Loss of thrombomodulin in placental dysfunction in preeclampsia","volume":"36","author":"Turner","year":"2016","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"issue":"2","key":"10.1016\/j.placenta.2018.03.006_bib16","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s12185-015-1899-5","article-title":"The efficacy of the administration of recombinant human soluble thrombomodulin in patients with DIC","volume":"103","author":"Aota","year":"2016","journal-title":"Int. J. Hematol."},{"issue":"7","key":"10.1016\/j.placenta.2018.03.006_bib17","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.placenta.2003.12.006","article-title":"Histologic features of placentas and abortion specimens from women with antiphospholipid and antiphospholipid-like syndromes","volume":"25","author":"Van Horn","year":"2004","journal-title":"Placenta"},{"issue":"5","key":"10.1016\/j.placenta.2018.03.006_bib18","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1111\/jog.12323","article-title":"Thrombomodulin improves maternal and fetal conditions in an experimental pre-eclampsia rat model","volume":"40","author":"Shin","year":"2014","journal-title":"J.\u00a0Obstet. Gynaecol. Res."},{"issue":"1","key":"10.1016\/j.placenta.2018.03.006_bib19","first-page":"23","article-title":"Angiogenic factors in placentas from pregnancies complicated by fetal growth restriction (review)","volume":"6","author":"Gourvas","year":"2012","journal-title":"Mol. Med. Rep."},{"issue":"6","key":"10.1016\/j.placenta.2018.03.006_bib20","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1161\/HYPERTENSIONAHA.115.05883","article-title":"Placental-specific sFLT-1 e15a protein is increased in preeclampsia, antagonizes vascular endothelial growth factor signaling, and has antiangiogenic activity","volume":"66","author":"Palmer","year":"2015","journal-title":"Hypertension (Dallas, Tex: 1979)"},{"issue":"9","key":"10.1016\/j.placenta.2018.03.006_bib21","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1084\/jem.20061022","article-title":"Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction","volume":"203","author":"Girardi","year":"2006","journal-title":"J.\u00a0Exp. Med."},{"issue":"10","key":"10.1016\/j.placenta.2018.03.006_bib22","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1111\/j.1471-0528.1995.tb10849.x","article-title":"Sonographic, stereological and Doppler flow velocimetric assessments of placental maturity","volume":"102","author":"Burton","year":"1995","journal-title":"Br. J. Obstet. Gynaecol."},{"issue":"9","key":"10.1016\/j.placenta.2018.03.006_bib23","doi-asserted-by":"crossref","first-page":"2440","DOI":"10.1097\/01.ASN.0000135975.90889.60","article-title":"New aspects in the pathophysiology of preeclampsia","volume":"15","author":"Davison","year":"2004","journal-title":"J.\u00a0Am. Soc. Nephrol.: JASN (J. Am. Soc. Nephrol.)"},{"issue":"7","key":"10.1016\/j.placenta.2018.03.006_bib24","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1056\/NEJMoa031884","article-title":"Circulating angiogenic factors and the risk of preeclampsia","volume":"350","author":"Levine","year":"2004","journal-title":"N.\u00a0Engl. J. Med."},{"issue":"4","key":"10.1016\/j.placenta.2018.03.006_bib25","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1016\/j.ajog.2005.10.192","article-title":"Serum sFlt1 concentration during preeclampsia and mid trimester blood pressure in healthy nulliparous women","volume":"194","author":"Levine","year":"2006","journal-title":"Am. J. Obstet. Gynecol."},{"issue":"7","key":"10.1016\/j.placenta.2018.03.006_bib26","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1080\/14767050902801769","article-title":"Increased plasma soluble fms-like tyrosine kinase 1 and endoglin levels in pregnancies complicated with preeclampsia","volume":"22","author":"Chedraui","year":"2009","journal-title":"J.\u00a0Matern. Fetal Neonatal Med.: Off. J. Eur. Assoc. Perinatal Med., Fed. Asia Oceania Perinatal Soc., Inter. Soc. Perinatal Obs."},{"issue":"4","key":"10.1016\/j.placenta.2018.03.006_bib27","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.2353\/ajpath.2007.060465","article-title":"Thrombin regulates soluble fms-like tyrosine kinase-1 (sFlt-1) expression in first trimester decidua: implications for preeclampsia","volume":"170","author":"Lockwood","year":"2007","journal-title":"Am. J. Pathol."},{"issue":"1","key":"10.1016\/j.placenta.2018.03.006_bib28","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s00281-011-0282-8","article-title":"Thrombomodulin and its role in inflammation","volume":"34","author":"Conway","year":"2012","journal-title":"Semin. Immunopathol."},{"issue":"12","key":"10.1016\/j.placenta.2018.03.006_bib29","doi-asserted-by":"crossref","first-page":"H1585","DOI":"10.1152\/ajpheart.00096.2013","article-title":"Thrombomodulin and the vascular endothelium: insights into functional, regulatory, and therapeutic aspects","volume":"304","author":"Martin","year":"2013","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"issue":"2","key":"10.1016\/j.placenta.2018.03.006_bib30","first-page":"718","article-title":"Recombinant thrombomodulin and activated protein C in the treatment of disseminated intravascular coagulation","volume":"82","author":"Maruyama","year":"1999","journal-title":"Thromb. Haemostasis"},{"issue":"4","key":"10.1016\/j.placenta.2018.03.006_bib31","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1160\/TH08-10-0632","article-title":"Protection of vascular barrier integrity by activated protein C in murine models depends on protease-activated receptor-1","volume":"101","author":"Schuepbach","year":"2009","journal-title":"Thromb. Haemostasis"},{"issue":"1","key":"10.1016\/j.placenta.2018.03.006_bib32","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/j.1538-7836.2006.02267.x","article-title":"Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: results of a phase III, randomized, double-blind clinical trial","volume":"5","author":"Saito","year":"2007","journal-title":"J.\u00a0Throm. and Haemost.: JTH"},{"issue":"3","key":"10.1016\/j.placenta.2018.03.006_bib33","doi-asserted-by":"crossref","first-page":"e238","DOI":"10.1016\/j.thromres.2010.05.002","article-title":"Use of recombinant human soluble thrombomodulin in the management of HELLP syndrome complicated by DIC","volume":"126","author":"Ikezoe","year":"2010","journal-title":"Thromb. Res."},{"issue":"5","key":"10.1016\/j.placenta.2018.03.006_bib34","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1177\/1076029612443305","article-title":"Efficacy of recombinant human soluble thrombomodulin in severe postpartum hemorrhage with disseminated intravascular coagulation","volume":"19","author":"Sugawara","year":"2013","journal-title":"Clin. Appl. Throm.\/Hemos.: Off. J. Intern. Acad. Clin. Appl. Thromb.\/Hemos."}],"container-title":["Placenta"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0143400418300845?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0143400418300845?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T17:57:13Z","timestamp":1758909433000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0143400418300845"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5]]},"references-count":34,"alternative-id":["S0143400418300845"],"URL":"https:\/\/doi.org\/10.1016\/j.placenta.2018.03.006","relation":{},"ISSN":["0143-4004"],"issn-type":[{"value":"0143-4004","type":"print"}],"subject":[],"published":{"date-parts":[[2018,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Recombinant human soluble thrombomodulin as an anticoagulation therapy improves recurrent miscarriage and fetal growth restriction due to placental insufficiency \u2013 The leading cause of preeclampsia","name":"articletitle","label":"Article Title"},{"value":"Placenta","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.placenta.2018.03.006","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}]}}