{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:18:29Z","timestamp":1787008709038,"version":"build-2736575974"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,10,31]],"date-time":"2021-10-31T00:00:00Z","timestamp":1635638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p\/>\n                  <jats:sec>\n                    <jats:title>OBJECTIVES<\/jats:title>\n                    <jats:p>To evaluate the competing pro-haemorrhagic contribution of acquired von Willebrand (vW) disease and antithrombotic therapy in patients implanted with continuous-flow left ventricular assist devices (LVADs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We compared the extent of vW factor (vWf) degradation [vWf antigen (vWf:Ag)] and a decrease of functional activity of large vWf multimers [vWf collagen binding (vWf:CB)] in LVAD patients who did and did not suffer from bleeding. Data were measured pre-implant, at short-term (t1: &amp;lt;3 months) and long-term (t2: &amp;gt;12 months) follow-up. The occurrence of primary bleeding events, as well as bleeding recurrence, was correlated with patient-specific vWf profile and antithrombotic regimen. Indeed, patients were discharged on warfarin (international normalized ratio: 2\u20132.5) and aspirin, with the latter withhold after a first bleeding episode.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Fifty-three patients were enrolled. The median follow-up was 324 (226\u2013468) days. We recorded 25 primary bleeding events (47% of patients). All primary events occurred in patients on warfarin and aspirin. Both vWf:Ag and vWf:CB decreased significantly post-implant (P = 0.0003 and P &amp;lt; 0.0001), and patients showing pathological vWf:CB\/vWf:Ag ratio (&amp;lt;0.7) increased progressively over the time of support (pre-implant = 26%, t1 = 58%, t2 = 74%; P &amp;lt; 0.0001). Of note, activity of large vWf multimers of bleeders was significantly lower at t2 with respect to non-bleeders (vWf:CB: 61 (36\u2013115) vs 100 (68\u2013121), P = 0.04; vWf:CB\/vWf:Ag ratio: 0.36 (0.26\u20130.61) vs 0.58 (0.33\u20130.96), P = 0.04). Despite these marked differences in the vWf profile, following aspirin discontinuation only 3 patients had bleeding recurrence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>Aspirin contributes significantly to haemorrhagic events in the background of acquired vW disease; its discontinuation significantly reduces bleeding recurrence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03255928; ClinicalTrials.gov Identifier: NCT03255928.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejcts\/ezab474","type":"journal-article","created":{"date-parts":[[2021,10,16]],"date-time":"2021-10-16T07:32:22Z","timestamp":1634369542000},"source":"Crossref","is-referenced-by-count":11,"title":["Bleeding in patients with continuous-flow left ventricular assist devices: acquired von Willebrand disease or antithrombotics?"],"prefix":"10.1093","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7948-3847","authenticated-orcid":false,"given":"Filippo","family":"Consolo","sequence":"first","affiliation":[{"name":"Universit\u00e0 Vita Salute San Raffaele , Milano, Italy"},{"name":"Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute , Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7992-5222","authenticated-orcid":false,"given":"Alessandra","family":"Marasi","sequence":"additional","affiliation":[{"name":"Dipartimento di Elettronica Informazione e Bioingengeria, Politecnico di Milano , Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2790-3088","authenticated-orcid":false,"given":"Patrizia","family":"Della Valle","sequence":"additional","affiliation":[{"name":"Coagulation Service and Thrombosis Research Unit, IRCCS San Raffaele Scientific Institute , Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3667-0965","authenticated-orcid":false,"given":"Marta","family":"Bonora","sequence":"additional","affiliation":[{"name":"Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute , Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Pieri","sequence":"additional","affiliation":[{"name":"Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute , Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Mara","family":"Scandroglio","sequence":"additional","affiliation":[{"name":"Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute , Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Redaelli","sequence":"additional","affiliation":[{"name":"Dipartimento di Elettronica Informazione e Bioingengeria, Politecnico di Milano , Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7687-7648","authenticated-orcid":false,"given":"Alberto","family":"Zangrillo","sequence":"additional","affiliation":[{"name":"Universit\u00e0 Vita Salute San Raffaele , Milano, Italy"},{"name":"Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute , Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9857-4509","authenticated-orcid":false,"given":"Armando","family":"D\u2019Angelo","sequence":"additional","affiliation":[{"name":"Coagulation Service and Thrombosis Research Unit, IRCCS San Raffaele Scientific Institute , Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Pappalardo","sequence":"additional","affiliation":[{"name":"Cardiothoracic and Vascular Anesthesia and Intensive Care, AO SS. Antonio e Biagio e Cesare Arrigo , Alessandria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,10,31]]},"reference":[{"key":"2022070609165535300_ezab474-B1","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1161\/CIRCRESAHA.119.313574","article-title":"Use of ventricular assist devices and heart transplantation for advanced heart failure","volume":"124","author":"Miller","year":"2019","journal-title":"Circ Res"},{"key":"2022070609165535300_ezab474-B2","doi-asserted-by":"crossref","DOI":"10.1016\/j.athoracsur.2020.12.038","article-title":"The society of thoracic surgeons intermacs 2020 annual report","author":"Molina","year":"2021","journal-title":"Ann Thorac Surg"},{"key":"2022070609165535300_ezab474-B3","doi-asserted-by":"crossref","first-page":"e006252","DOI":"10.1161\/CIRCHEARTFAILURE.119.006252","article-title":"Long-term survival of patients with advanced heart failure receiving an left ventricular assist device intended as a bridge to transplantation: the registry to evaluate the HeartWare left ventricular assist system","volume":"13","author":"Zimpfer","year":"2020","journal-title":"Circ Heart Fail"},{"key":"2022070609165535300_ezab474-B4","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1056\/NEJMoa1900486","article-title":"A fully magnetically levitated left ventricular assist device\u2014final report","volume":"380","author":"Mehra","year":"2019","journal-title":"N Engl J Med"},{"key":"2022070609165535300_ezab474-B5","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.jtcvs.2014.09.031","article-title":"Pathologic von Willebrand factor degradation with a left ventricular assist device occurs via two distinct mechanisms: mechanical demolition and enzymatic cleavage","volume":"149","author":"Bartoli","year":"2015","journal-title":"J Thorac Cardiovasc Surg"},{"key":"2022070609165535300_ezab474-B6","doi-asserted-by":"crossref","first-page":"3133","DOI":"10.1182\/blood-2015-10-636480","article-title":"Acquired von Willebrand syndrome associated with left ventricular assist device","volume":"127","author":"Nascimbene","year":"2016","journal-title":"Blood"},{"key":"2022070609165535300_ezab474-B7","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/j.healun.2017.06.004","article-title":"von Willebrand factor disruption and continuous-flow circulatory devices","volume":"36","author":"Proudfoot","year":"2017","journal-title":"J Heart Lung Transplant"},{"key":"2022070609165535300_ezab474-B8","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.healun.2021.01.012","article-title":"Safety of reduced anti-thrombotic strategy in patients with HeartMate 3 left ventricular assist device","volume":"40","author":"Marshall","year":"2021","journal-title":"J Heart Lung Transplant"},{"key":"2022070609165535300_ezab474-B9","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.healun.2020.03.001","article-title":"Effect of aspirin dose on hemocompatibility-related outcomes with a magnetically levitated left ventricular assist device: an analysis from the MOMENTUM 3 study","volume":"39","author":"Saeed","year":"2020","journal-title":"J Heart Lung Transplant"},{"key":"2022070609165535300_ezab474-B10","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.healun.2020.03.019","article-title":"Is aspirin needed to prevent thrombotic events in patients treated with a HeartMate 3 left ventricular assist device?","volume":"39","author":"Gustafsson","year":"2020","journal-title":"J Heart Lung Transplant"},{"key":"2022070609165535300_ezab474-B11","doi-asserted-by":"crossref","first-page":"S48","DOI":"10.1016\/j.healun.2020.01.1222","article-title":"Discontinuation of aspirin in HeartMate 3: long-term outcomes","volume":"39","author":"Lim","year":"2020","journal-title":"J Heart Lung Transplant"},{"key":"2022070609165535300_ezab474-B12","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1097\/MAT.0000000000001064","article-title":"Influence of different antithrombotic regimens on platelet-mediated thrombin generation in patients with left ventricular assist devices","volume":"66","author":"Consolo","year":"2020","journal-title":"ASAIO J"},{"key":"2022070609165535300_ezab474-B13","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1002\/ejhf.1468","article-title":"Do we need aspirin in HeartMate 3 patients?","volume":"21","author":"Consolo","year":"2019","journal-title":"Eur J Heart Fail"},{"key":"2022070609165535300_ezab474-B14"},{"key":"2022070609165535300_ezab474-B15","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.thromres.2015.12.010","article-title":"Evaluation of a von Willebrand factor three test panel and chemiluminescent-based assay system for identification of, and therapy monitoring in, von Willebrand disease","volume":"141","author":"Favaloro","year":"2016","journal-title":"Thromb Res"},{"key":"2022070609165535300_ezab474-B16","first-page":"1255","article-title":"Shear-mediated platelet activation in patients implanted with continuous flow LVADs: a preliminary study utilizing the platelet activity state (PAS) assay","volume":"2015","author":"Valerio","year":"2015","journal-title":"Annu Int Conf IEEE Eng Med Biol Soc"},{"key":"2022070609165535300_ezab474-B17","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1002\/ejhf.1113","article-title":"Platelet activation is a preoperative risk factor for the development of thromboembolic complications in patients with continuous-flow left ventricular assist device","volume":"20","author":"Consolo","year":"2018","journal-title":"Eur J Heart Fail"},{"key":"2022070609165535300_ezab474-B18","doi-asserted-by":"crossref","first-page":"e33","DOI":"10.1097\/MAT.0000000000000842","article-title":"Shear-mediated platelet activation enhances thrombotic complications in patients with LVADs and is reversed after heart transplantation","volume":"65","author":"Consolo","year":"2019","journal-title":"ASAIO J"},{"key":"2022070609165535300_ezab474-B19","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/cc2428","article-title":"Statistics review 8: qualitative data\u2014tests of association","volume":"8","author":"Bewick","year":"2004","journal-title":"Crit Care"},{"key":"2022070609165535300_ezab474-B20","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1093\/ejcts\/ezu510","article-title":"Platelet dysfunction and acquired von Willebrand syndrome in patients with left ventricular assist devices","volume":"48","author":"Baghai","year":"2015","journal-title":"Eur J Cardiothorac Surg"},{"key":"2022070609165535300_ezab474-B21","doi-asserted-by":"crossref","first-page":"e006519","DOI":"10.1161\/JAHA.117.006519","article-title":"Platelet secretion defects and acquired von Willebrand Syndrome in patients with ventricular assist devices","author":"Geisen","year":"2018","journal-title":"J Am Heart Assoc"},{"key":"2022070609165535300_ezab474-B22","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/j.healun.2019.05.006","article-title":"Effects of a fully magnetically levitated centrifugal-flow or axial-flow left ventricular assist device on von Willebrand factor: a prospective multicenter clinical trial","volume":"38","author":"Bansal","year":"2019","journal-title":"J Heart Lung Transplant"},{"key":"2022070609165535300_ezab474-B23","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1093\/ejcts\/ezz045","article-title":"Acquired von Willebrand factor deficiency is reduced in HeartMate 3 patients","volume":"56","author":"Klaeske","year":"2019","journal-title":"Eur J Cardiothorac Surg"},{"key":"2022070609165535300_ezab474-B24","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.healun.2018.03.002","article-title":"Evaluation of low-intensity anti-coagulation with a fully magnetically levitated centrifugal-flow circulatory pump-the MAGENTUM 1 study","volume":"37","author":"Netuka","year":"2018","journal-title":"J Heart Lung Transplant"},{"key":"2022070609165535300_ezab474-B25","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1016\/j.athoracsur.2016.07.072","article-title":"Outcomes in HeartMate II Patients with no antiplatelet therapy: 2-year results from the European TRACE study","volume":"103","author":"Netuka","year":"2017","journal-title":"Ann Thorac Surg"},{"key":"2022070609165535300_ezab474-B26","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1161\/CIRCULATIONAHA.118.037231","article-title":"Comprehensive analysis of stroke in the long-term Cohort of the MOMENTUM 3 Study","volume":"139","author":"Colombo","year":"2019","journal-title":"Circulation"},{"key":"2022070609165535300_ezab474-B27","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1097\/MBC.0b013e32834a7e01","article-title":"Diagnosis and classification of von Willebrand disease: a review of the differential utility of various functional von Willebrand factor assays","volume":"22","author":"Favaloro","year":"2011","journal-title":"Blood Coagul Fibrinolysis"},{"key":"2022070609165535300_ezab474-B28","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1016\/j.amjcard.2020.12.018","article-title":"Overview of aspirin and platelet biology","volume":"144","author":"Santos-Gallego","year":"2021","journal-title":"Am J Cardiol"}],"container-title":["European Journal of Cardio-Thoracic Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ejcts\/article-pdf\/62\/1\/ezab474\/44411759\/ezab474.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejcts\/article-pdf\/62\/1\/ezab474\/44411759\/ezab474.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T05:21:14Z","timestamp":1657084874000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejcts\/article\/doi\/10.1093\/ejcts\/ezab474\/6414863"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,31]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,6,15]]}},"URL":"https:\/\/doi.org\/10.1093\/ejcts\/ezab474","relation":{},"ISSN":["1010-7940","1873-734X"],"issn-type":[{"value":"1010-7940","type":"print"},{"value":"1873-734X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,7,1]]},"published":{"date-parts":[[2021,10,31]]},"article-number":"ezab474"}}