{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T16:54:19Z","timestamp":1758905659016,"version":"3.41.2"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T00:00:00Z","timestamp":1625529600000},"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. Cardiovasc. Med."],"abstract":"<jats:p><jats:bold>Background and Rationale:<\/jats:bold> Mild therapeutic hypothermia (MTH) is a concept to reduce infarct size and improve outcome after ST-segment elevation myocardial infarction (STEMI). In the STATIM trial, we investigated MTH as an additional therapy for STEMI patients. In the intention-to-treat set, 101 patients were included. No difference in primary and secondary endpoints measured by cardiac magnetic resonance imaging was found. Platelet activation and plasmatic coagulation are key in the pathophysiology of STEMI. In the present study, we investigated the effect of MTH on primary and secondary hemostasis in STEMI patients.<\/jats:p><jats:p><jats:bold>Methods and Results:<\/jats:bold> Platelet function and morphology were assessed by routine blood count, aggregometry testing, and flow cytometry. Soluble platelet markers were determined by enzyme-linked immunosorbent assay (ELISA) testing. Plasmatic coagulation was measured throughout the study. Platelet count remained unchanged, irrespective of treatment, whereas platelet size decreased in both patient groups. Platelet aggregometry indicated increased platelet reactivity in the MTH group. Furthermore, higher adenosine diphosphate (ADP) plasma levels were found in MTH patients. Expression of glycoprotein IIb\/IIIa was increased on platelets of STEMI patients treated with MTH. Lower patient temperatures correlated with longer clotting times and resulted in reduced pH. Lower pH values were positively correlated with longer clotting times.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Present data indicate longer clotting times and higher platelet reactivity in STEMI patients treated with MTH. These changes did not correspond to clinical bleeding events or larger infarct size.<\/jats:p>","DOI":"10.3389\/fcvm.2021.707367","type":"journal-article","created":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T12:39:27Z","timestamp":1625575167000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Mild Therapeutic Hypothermia Alters Hemostasis in ST Elevation Myocardial Infarction Patients"],"prefix":"10.3389","volume":"8","author":[{"given":"Thomas","family":"Scherz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas M.","family":"Hofbauer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna S.","family":"Ondracek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Simon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fritz","family":"Sterz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Testori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene M.","family":"Lang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Mangold","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1959","DOI":"10.1161\/CIRCRESAHA.114.302782","article-title":"Global perspective on acute coronary syndrome: a burden on the young and poor","volume":"114","author":"Vedanthan","year":"2014","journal-title":"Circ Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1093\/ehjci\/jes271","article-title":"Final infarct size measured by cardiovascular magnetic resonance in patients with ST elevation myocardial infarction predicts long-term clinical outcome: an observational study","volume":"14","author":"Lonborg","year":"2013","journal-title":"Eur Heart J Cardiovasc Imaging."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2007","DOI":"10.1001\/archinte.161.16.2007","article-title":"Hyperthermia after cardiac arrest is associated with an unfavorable neurologic outcome","volume":"161","author":"Zeiner","year":"2001","journal-title":"Arch Intern Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.jstrokecerebrovasdis.2008.09.015","article-title":"Combined neuroprotective modalities coupled with thrombolysis in acute ischemic stroke: a pilot study of caffeinol and mild hypothermia","volume":"18","author":"Martin-Schild","year":"2009","journal-title":"J Stroke Cerebrovasc Dis."},{"key":"B5","doi-asserted-by":"publisher","first-page":"CD003311","DOI":"10.1002\/14651858.CD003311.pub3","article-title":"Cooling for newborns with hypoxic ischaemic encephalopathy","volume":"2013","author":"Jacobs","year":"2013","journal-title":"Cochrane Database Syst Rev."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1857","DOI":"10.1016\/j.jacc.2013.12.027","article-title":"Rapid endovascular catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction","volume":"63","author":"Erlinge","year":"2014","journal-title":"J Am Coll Cardiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e531","DOI":"10.4244\/EIJ-D-17-00279","article-title":"COOL AMI EU pilot trial: a multicentre, prospective, randomised controlled trial to assess cooling as an adjunctive therapy to percutaneous intervention in patients with acute myocardial infarction","volume":"13","author":"Noc","year":"2017","journal-title":"EuroIntervention."},{"key":"B8","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1161\/CIRCINTERVENTIONS.110.957902","article-title":"A pilot study of rapid cooling by cold saline and endovascular cooling before reperfusion in patients with ST-elevation myocardial infarction","volume":"3","author":"G\u00f6tberg","year":"2010","journal-title":"Circ Cardiovasc Interv."},{"key":"B9","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1177\/1074248410387280","article-title":"Mild hypothermia as a cardioprotective approach for acute myocardial infarction: laboratory to clinical application","volume":"16","author":"Hale","year":"2011","journal-title":"J Cardiovasc Pharmacol Ther."},{"key":"B10","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1161\/CIR.0000000000000262","article-title":"Part 8: post\u2013cardiac arrest care","volume":"132","author":"Callaway","year":"2015","journal-title":"Circulation."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2197","DOI":"10.1056\/NEJMoa1310519","article-title":"Targeted temperature management at 33degreeC versus 36degreeC after cardiac arrest","volume":"369","author":"Nielsen","year":"2013","journal-title":"NEJM."},{"key":"B12","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1136\/heartjnl-2015-308559","article-title":"Therapeutic hypothermia in ST elevation myocardial infarction: a systematic review and meta-analysis of randomised control trials","volume":"102","author":"Villablanca","year":"2016","journal-title":"Heart."},{"key":"B13","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1136\/heartjnl-2018-313705","article-title":"Out-of-hospital initiation of hypothermia in ST-segment elevation myocardial infarction: a randomised trial","volume":"105","author":"Testori","year":"2018","journal-title":"Heart."},{"key":"B14","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/j.jcmg.2017.05.023","article-title":"Long-Term incremental prognostic value of cardiovascular magnetic resonance after ST-segment elevation myocardial infarction","volume":"11","author":"Symons","year":"2018","journal-title":"JACC Cardiovasc Imaging."},{"key":"B15","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.resuscitation.2015.11.007","article-title":"Changes in coagulation during therapeutic hypothermia in cardiac arrest patients","volume":"98","author":"Nielsen","year":"2016","journal-title":"Resuscitation."},{"key":"B16","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1016\/j.resuscitation.2009.03.026","article-title":"Hemostasis in cardiac arrest patients treated with mild hypothermia initiated by cold fluids","volume":"80","author":"Spiel","year":"2009","journal-title":"Resuscitation."},{"key":"B17","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.thromres.2015.04.029","article-title":"The impact of therapeutic hypothermia on on-treatment platelet reactivity and clinical outcome in cardiogenic shock patients undergoing primary PCI for acute myocardial infarction: results from the ISAR-SHOCK registry","volume":"136","author":"Orban","year":"2015","journal-title":"Thromb Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2736","DOI":"10.1161\/CIRCULATIONAHA.110.009449","article-title":"Standardized bleeding definitions for cardiovascular clinical trials a consensus report from the bleeding academic research consortium","volume":"123","author":"Cutlip","year":"2011","journal-title":"Circulation."},{"key":"B19","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1002\/cyto.a.22455","article-title":"Standardized flow cytometry assay for identification of human monocytic heterogeneity and LRP1 expression in monocyte subpopulations: decreased expression of this receptor in nonclassical monocytes","volume":"85","author":"Ferrer","year":"2014","journal-title":"Cytom Part A."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1016\/j.jacc.2014.06.1194","article-title":"Comprehensive prognosis assessment by CMR imaging after ST-segment elevation myocardial infarction","volume":"64","author":"Eitel","year":"2014","journal-title":"J Am Coll Cardiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.atherosclerosis.2006.01.021","article-title":"The effects of simvastatin, losartan, and combined therapy on soluble CD40 ligand in hypercholesterolemic, hypertensive patients","volume":"190","author":"Han","year":"2007","journal-title":"Atherosclerosis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2118","DOI":"10.1161\/01.CIR.102.17.2118","article-title":"Angiotensin II induces leukocyte-endothelial cell interactions in vivo via AT1 and AT2 receptor-mediated P-selectin upregulation","volume":"102","author":"Piqueras","year":"2000","journal-title":"Circulation."},{"key":"B23","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1089\/ther.2014.0005","article-title":"Wide Temperature range testing with ROTEM coagulation analyses","volume":"4","author":"Kander","year":"2014","journal-title":"Ther Hypothermia Temp Manag."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1016\/j.resuscitation.2014.07.018","article-title":"Therapeutic temperature management after cardiac arrest and the risk of bleeding: systematic review and meta-analysis","volume":"85","author":"Stockmann","year":"2014","journal-title":"Resuscitation."},{"key":"B25","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/j.resuscitation.2015.08.018","article-title":"The effect of targeted temperature management on coagulation parameters and bleeding events after out-of-hospital cardiac arrest of presumed cardiac cause","volume":"96","author":"Jacob","year":"2015","journal-title":"Resuscitation."},{"key":"B26","doi-asserted-by":"publisher","first-page":"44","DOI":"10.3109\/09537100903420269","article-title":"Mild and moderate hypothermia increases platelet aggregation induced by various agonists: a whole blood in vitro study","volume":"21","author":"Scharbert","year":"2010","journal-title":"Platelets."},{"key":"B27","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1186\/s13054-016-1302-9","article-title":"Influence of temperature on thromboelastometry and platelet aggregation in cardiac arrest patients undergoing targeted temperature management","volume":"20","author":"Jeppesen","year":"2016","journal-title":"Crit Care."},{"key":"B28","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1182\/blood.V85.7.1796.bloodjournal8571796","article-title":"Mechanism of shape change in chilled human platelets","volume":"85","author":"Winokur","year":"1995","journal-title":"Blood."},{"key":"B29","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/S0092-8674(02)01253-9","article-title":"The clearance mechanism of chilled blood platelets","volume":"112","author":"Hoffmeister","year":"2003","journal-title":"Cell."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1579","DOI":"10.1097\/00000542-199806000-00022","article-title":"In vitro hypothermia enhances platelet GPIIb-IIIa activation and P-selectin expression","volume":"88","author":"Faraday","year":"1995","journal-title":"Anesthesiology."},{"key":"B31","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1161\/CIRCINTERVENTIONS.112.972323","article-title":"Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in patients with ST-segment-elevation myocardial infarction","volume":"5","author":"Alexopoulos","year":"2012","journal-title":"Circ Cardiovasc Interv."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1601","DOI":"10.1016\/j.jacc.2013.01.024","article-title":"Comparison of prasugrel and ticagrelor loading doses in ST-segment elevation myocardial infarction patients: RAPID (rapid activity of platelet inhibitor drugs) primary PCI study","volume":"61","author":"Parodi","year":"2013","journal-title":"J Am Coll Cardiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1607","DOI":"10.1161\/ATVBAHA.111.226373","article-title":"Evidence of platelet activation at medically used hypothermia and mechanistic data indicating ADP as a key mediator and therapeutic target","volume":"31","author":"Straub","year":"2011","journal-title":"Arterioscler Thromb Vasc Biol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1097\/EJA.0b013e3283333a7d","article-title":"Haemodynamic consequences of mild therapeutic hypothermia after cardiac arrest","volume":"27","author":"Bergman","year":"2010","journal-title":"Eur J Anaesthesiol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1097\/00003246-199701000-00011","article-title":"Type B lactic acidosis following cardiopulmonary bypass","volume":"25","author":"Raper","year":"1997","journal-title":"Crit Care Med."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1016\/0003-4975(93)90014-9","article-title":"Effects of pH on brain energetics after hypothermic circulatory arrest","volume":"55","author":"Aoki","year":"1993","journal-title":"Ann Thorac Surg."},{"key":"B37","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1097\/TA.0b013e3181a602a7","article-title":"Coagulopathy by hypothermia and acidosis: mechanisms of thrombin generation and fibrinogen availability","volume":"67","author":"Martini","year":"2009","journal-title":"J Trauma - Inj Infect Crit Care."}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2021.707367\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T12:39:29Z","timestamp":1625575169000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2021.707367\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,6]]},"references-count":37,"alternative-id":["10.3389\/fcvm.2021.707367"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2021.707367","relation":{},"ISSN":["2297-055X"],"issn-type":[{"type":"electronic","value":"2297-055X"}],"subject":[],"published":{"date-parts":[[2021,7,6]]},"article-number":"707367"}}