{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:00:09Z","timestamp":1790172009223,"version":"4.1.0"},"reference-count":12,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp;amp; Cancer"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pediatric thromboembolism is increasingly encountered in critical care. Systemic thrombolysis with tissue plasminogen activator (tPA) facilitates vessel or valve patency, yet pediatric\u2010specific protocols remain undefined, and safety concerns persist.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the efficacy and safety of a tailored, prolonged systemic tPA protocol for vessel thrombosis and mechanical valve obstruction in infants and children, and to characterize D\u2010dimer kinetics by indication.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This retrospective cohort study was performed in a tertiary pediatric cardiac ICU (from July 2014 to March 2024). Extracted data included demographics, tPA dosing, laboratory trends, transfusion requirements, imaging\u2010confirmed success, and adverse events. D\u2010dimer trajectories were analyzed using Welch's\n                      <jats:italic>t<\/jats:italic>\n                      \u2010test.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty\u2010two patients received systemic tPA during the study period. Median age was 287\u00a0days (IQR: 64.8\u2013940); 32% were less than 90\u00a0days old. Indications included stuck mechanical valve (\n                      <jats:italic>n<\/jats:italic>\n                      = 10), central venous thrombosis with chylothorax (\n                      <jats:italic>n<\/jats:italic>\n                      = 7), large venous thrombosis (\n                      <jats:italic>n<\/jats:italic>\n                      = 3), coronary thrombosis (\n                      <jats:italic>n<\/jats:italic>\n                      = 1), and arterial ischemic stroke (\n                      <jats:italic>n<\/jats:italic>\n                      = 1). Median initial tPA dose was 0.1\u00a0mg\/kg\/h (IQR: 0.06\u20130.1), with escalation up to 0.5\u00a0mg\/kg\/h in selected cases; mean treatment duration was 3.9 \u00b1 2.8\u00a0days. Valve mobility was restored in 80%. Complete thrombus resolution was achieved in all venous, coronary, and stroke cases. Minor bleeding occurred in 23%; one subdural hemorrhage (5%) was observed. All patients survived to discharge. D\u2010dimer kinetics differed significantly between vessel thrombosis and mechanical valve obstruction (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.01), demonstrating distinct fibrinolytic profiles.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Tailored prolonged systemic tPA appears effective with minimal adverse effects when administered under strict monitoring. Distinct D\u2010dimer patterns may aid treatment guidance. Multicenter studies are needed to validate standardized pediatric protocols.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/1545-5017.70638","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T07:25:40Z","timestamp":1788420340000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety and Effectiveness of a High\u2010Dose, Tailored Tissue Plasminogen Activator Therapy Protocol: A Joint Pediatric Hematology and Cardiac ICU Quality Improvement Initiative Analysis"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7582-2218","authenticated-orcid":false,"given":"Eran","family":"Shostak","sequence":"first","affiliation":[{"name":"Pediatric Cardiac Intensive Care Unit Schneider Children's Medical Center of Israel  Petah Tikva Israel"},{"name":"Gray Faculty of Medical and Health Sciences Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oded","family":"Gilad","sequence":"additional","affiliation":[{"name":"Gray Faculty of Medical and Health Sciences Tel Aviv University  Tel Aviv Israel"},{"name":"Rina Zaizov Department of Pediatric Hematology\u2010Oncology Schneider Children's Medical Center of Israel  Petah Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4330-1658","authenticated-orcid":false,"given":"Yael","family":"Feinstein","sequence":"additional","affiliation":[{"name":"Pediatric Cardiac Intensive Care Unit Schneider Children's Medical Center of Israel  Petah Tikva Israel"},{"name":"Dina Reccanati School of Medicine Reichman University  Herzliya Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigal","family":"Nakav","sequence":"additional","affiliation":[{"name":"Coagulation and Hemostasis Laboratory, Rabin Medical Center Beilinson Hospital  Petah Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4607-1133","authenticated-orcid":false,"given":"Ofer","family":"Schiller","sequence":"additional","affiliation":[{"name":"Pediatric Cardiac Intensive Care Unit Schneider Children's Medical Center of Israel  Petah Tikva Israel"},{"name":"Gray Faculty of Medical and Health Sciences Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3763-5694","authenticated-orcid":false,"given":"Joanne","family":"Yacobovich","sequence":"additional","affiliation":[{"name":"Gray Faculty of Medical and Health Sciences Tel Aviv University  Tel Aviv Israel"},{"name":"Rina Zaizov Department of Pediatric Hematology\u2010Oncology Schneider Children's Medical Center of Israel  Petah Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2017.00260"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0b013e32831ef537"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000436140.77832.7a"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1067\/mpd.2001.118428"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2021.814033"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0b013e318047b78b"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000004025"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.11-2308"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000002031"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073811421827"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2012.10.016"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2015.04.025"}],"container-title":["Pediatric Blood &amp; 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