{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:37:20Z","timestamp":1792442240316,"version":"4.5.0"},"reference-count":12,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T00:00:00Z","timestamp":1649808000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Septic peritonitis is associated with significant morbidity and mortality. As a potential therapeutic agent in the treatment of sepsis, 2-O, 3-O desulfated heparin (ODSH) reduces histones and platelet factor 4 (PF4) in mouse sepsis models. This pilot clinical trial evaluated the safety and effect of ODSH in client-owned dogs with septic peritonitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interventions<\/jats:title><jats:p>In an IACUC-approved, open-label, prospective, dose-escalation clinical trial in 6 dogs with spontaneous septic peritonitis, ODSH administration was initiated following surgical explore to achieve source control. <jats:underline>A<\/jats:underline>cute <jats:underline>p<\/jats:underline>atient <jats:underline>p<\/jats:underline>hysiology and <jats:underline>l<\/jats:underline>aboratory <jats:underline>e<\/jats:underline>valuation (APPLE<jats:sub>fast<\/jats:sub> and APPLE<jats:sub>full<\/jats:sub>) scores on admission, source of septic peritonitis, requirement for vasopressors, the administration of blood products, and survival to discharge were recorded. Platelet count, cell free DNA (cfDNA) concentration, and platelet factor 4 (PF4) concentrations were measured at the time of each ODSH dosage. A dose of ODSH was administered every 8 hs for a total of 4 doses (maximum total dosage 75 mg\/kg) based on a pre-determined escalation protocol. Patients were monitored in the ICU following administration for evidence of clinical hemorrhage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Results<\/jats:title><jats:p>The mean APPLE<jats:sub>fast<\/jats:sub> and APPLE<jats:sub>full<\/jats:sub> scores on admission were 22 +\/- 6 and 32 +\/-10, respectively. Four dogs received 4 total dosages of ODSH and 2 dogs received 3 total dosages of ODSH intravenously. The mean total dosage of ODSH administered during the study period was 48.3 +\/- 21.6 mg\/kg. No dog required dose de-escalation or had any evidence of bleeding. Four dogs survived to discharge.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>No adverse effects of ODSH administration were documented in dogs with septic peritonitis. A randomized controlled trial is necessary to evaluate ODSH as a novel therapeutic in the treatment of septic peritonitis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fvets.2022.862308","type":"journal-article","created":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T09:31:27Z","timestamp":1649842287000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Dose Escalation Trial of Desulfated Heparin (ODSH) in Septic Peritonitis"],"prefix":"10.3389","volume":"9","author":[{"given":"Katie D.","family":"Mauro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele P.","family":"Lambert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Anna","family":"Kowalska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent J.","family":"Thawley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mortimer","family":"Poncz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia M.","family":"Otto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"B2","first-page":"208","article-title":"Selective O-Desulfation Produces Nonanticoagulant Heparin that Retains Pharmacological Activity in the Lung","volume":"282","author":"Fryer","year":"1997","journal-title":"J Pharmacol Exp Ther"},{"key":"B3","doi-asserted-by":"publisher","first-page":"4020","DOI":"10.1038\/s41598-018-22156-5","article-title":"Neutrophil extracellular trap-microparticle complexes enhance thrombin generation via the intrinsic pathway of coagulation in mice","volume":"8","author":"Wang","year":"2018","journal-title":"Sci Rep"},{"key":"B4","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1097\/SHK.0000000000000221","article-title":"Neutrophil extracellular traps in sepsis","volume":"42","author":"Camicia","year":"2014","journal-title":"Shock"},{"key":"B5","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1161\/ATVBAHA.113.302236","article-title":"Modulation of protein c activation by histones, platelet factor 4, and heparinoids","volume":"34","author":"Kowalska","year":"2014","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1160\/TH11-11-0795","article-title":"Disruption of PF4\/H multimolecular complex formation with a minimally anticoagulant heparin (ODSH)","volume":"107","author":"Joglekar","year":"2012","journal-title":"Thromb Haemost"},{"key":"B7","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.ab.2005.08.035","article-title":"Titrimetric method for determination of O-desulfated heparin in physiological samples using protamine-sensitive membrane electrode as endpoint detector","volume":"346","author":"Buchanan","year":"2005","journal-title":"Anal Biochem"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1111\/j.1939-1676.2010.0552.x","article-title":"The acute patient physiologic and laboratory evaluation (APPLE) score: a severity of illness stratification system for hospitalized dogs","volume":"24","author":"Hayes","year":"2010","journal-title":"J Vet Intern Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1182\/blood.2019002329","article-title":"Fc-modified HIT-like monoclonal antibody as a novel treatment for sepsis","volume":"135","author":"Gollomp","year":"2020","journal-title":"Blood"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1735","DOI":"10.1378\/chest.06-2233","article-title":"Platelet count decline: an early prognostic marker in critically ill patients with prolonged ICU stays","volume":"131","author":"Moreau","year":"2007","journal-title":"Chest"},{"key":"B11","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1111\/vec.12628","article-title":"A pilot study evaluating the prognostic utility of platelet indices in dogs with septic peritonitis","volume":"27","author":"Llewellyn","year":"2017","journal-title":"J Vet Emerg Crit Care"},{"key":"B12","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1111\/vec.12592","article-title":"Measurement of plasma cell-free DNA concentrations in dogs with sepsis, trauma, and neoplasia","volume":"27","author":"Letendre","year":"2017","journal-title":"J Vet Emerg Crit Care"}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2022.862308\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T09:31:29Z","timestamp":1649842289000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2022.862308\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,13]]},"references-count":12,"alternative-id":["10.3389\/fvets.2022.862308"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2022.862308","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,13]]},"article-number":"862308"}}