{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T23:49:00Z","timestamp":1789775340284,"version":"4.0.1"},"reference-count":46,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cedars\u2013RECOOP Solidarity Fellowship","award":["#EFDS-FL2-02"],"award-info":[{"award-number":["#EFDS-FL2-02"]}]},{"name":"European Federation of Academies of Sciences and Humanities","award":["#EFDS-FL2-02"],"award-info":[{"award-number":["#EFDS-FL2-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>During pregnancy, the maternal hemostatic system undergoes significant changes to support placental angiogenesis, maintain fetal blood flow, and ensure safe delivery. This study investigates the dysregulation of hemostasis in placental insufficiency and explores potential markers for diagnosing and managing this gestational complication. Thromboelastography, coagulation and fibrinolysis functional assays, ELISA, and immunoblotting were employed to assess hemostasis dysregulation in placental dysfunction of two cohorts of pregnant women with placental dysfunction and healthy controls. Thromboelastographic analysis revealed no significant differences in clot lysis indices between the control and placental dysfunction groups, with values remaining within normal ranges, suggesting this method\u2019s limitations for assessing fibrinolysis in pregnancy. The placental dysfunction group demonstrated moderately increased fibrinogen levels and platelet sensitivity to ADP, indicating hemostasis reactiveness. Significantly lower D-dimer levels, decreased plasminogen activator inhibitor activity (total PAI-1 + PAI-2), and increased plasminogen activator activity, driven primarily by uPA in the placental dysfunction group, indicated abnormal fibrinolysis. Immunoblotting confirmed elevated uPA\/uPA-PAI complexes and reduced tPA\/tPA-PAI complexes, indicating that shutdown of tPA-mediated fibrinolysis and induction of uPA-driven vessel-wall-associated proteolysis are linked to placental dysfunction. Placental dysfunction involves fibrinolytic system dysregulation, marked by decreased PAI and tPA, uPA overproduction, and hypofibrinolysis, contributing to thrombotic risks, impaired placental flow, and complications like fetal growth retardation. PAI\/PA ratio and D-dimer levels have diagnostic potential for placental-dysfunction-associated complications.<\/jats:p>","DOI":"10.3390\/ijms26199339","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T08:56:44Z","timestamp":1758790604000},"page":"9339","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Placental Dysfunction Is Associated with Dysregulated Fibrinolytic System Activation"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8601-1939","authenticated-orcid":false,"given":"Tetiana","family":"Yatsenko","sequence":"first","affiliation":[{"name":"Palladin Institute of Biochemistry of NAS of Ukraine, 01054 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5782-8488","authenticated-orcid":false,"given":"Iryna","family":"Us","sequence":"additional","affiliation":[{"name":"Shupyk National Healthcare University of Ukraine, 04112 Kyiv, Ukraine"},{"name":"Kyiv Perinatal Center, 03150 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1249-3442","authenticated-orcid":false,"given":"Daria","family":"Korolova","sequence":"additional","affiliation":[{"name":"Palladin Institute of Biochemistry of NAS of Ukraine, 01054 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1565-8166","authenticated-orcid":false,"given":"Svitlana","family":"Zhuk","sequence":"additional","affiliation":[{"name":"Shupyk National Healthcare University of Ukraine, 04112 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halyna","family":"Dziuba","sequence":"additional","affiliation":[{"name":"Shupyk National Healthcare University of Ukraine, 04112 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4114-7821","authenticated-orcid":false,"given":"Alona","family":"Nalbat","sequence":"additional","affiliation":[{"name":"Palladin Institute of Biochemistry of NAS of Ukraine, 01054 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8581-6743","authenticated-orcid":false,"given":"Svitlana","family":"Kharchenko","sequence":"additional","affiliation":[{"name":"Palladin Institute of Biochemistry of NAS of Ukraine, 01054 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2962-2017","authenticated-orcid":false,"given":"Sandor George","family":"Vari","sequence":"additional","affiliation":[{"name":"International Research and Innovation in Medicine Program, Cedars\u2013Sinai Medical Center, Los Angeles, CA 90048, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6564-8823","authenticated-orcid":false,"given":"Volodymyr","family":"Chernyshenko","sequence":"additional","affiliation":[{"name":"Palladin Institute of Biochemistry of NAS of Ukraine, 01054 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1055\/s-2003-38897","article-title":"Hemostasis during Normal Pregnancy and Puerperium","volume":"29","author":"Hellgren","year":"2003","journal-title":"Semin. 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