{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:50:56Z","timestamp":1760244656478,"version":"build-2065373602"},"reference-count":19,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T00:00:00Z","timestamp":1670803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology of the People\u2019s Republic of China","award":["2020AAA0109604"],"award-info":[{"award-number":["2020AAA0109604"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>Acquired von Willebrand syndrome (AVWS) is caused by an acquired deficiency of von Willebrand factor (VWF), a multimeric protein required for primary hemostasis. For patients with heart valve diseases, high gradient across the malfunctioning valves could cause elevated shear stress and damage the most effective large VWF, eventually resulting in AVWS. However, AVWS has not been reported in association with normally functioning mechanical valves. Herein, we reported a 74-year-old female who suffered from recurrent gastrointestinal bleeding with a history of mechanical aortic and mitral valve replacement. This patient\u2019s function\/antigen ratio of VWF was decreased and gel electrophoresis revealed the loss of large VWF, which confirmed the diagnosis of AVWS. Echocardiogram showed that the function of the prostheses was normal. However, the gradient across aortic valve was increased due to a high cardiac state which is secondary to chronic anemia, resulting in the disruption of large VWF multimers and exacerbation of gastrointestinal (GI) bleeding. After managing the patient\u2019s anemia with transfusion, the gradient across the aortic valve had improved, with the resolution of GI bleeding. This is the first case report of AVWS that is associated with a normally functioning mechanical valve. AVWS should be considered one of the differential diagnoses if patients present with unexplained GI bleeding on the background of having prosthetic heart valves. The management of the underlying condition is essential.<\/jats:p>","DOI":"10.3390\/jcdd9120454","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T04:05:22Z","timestamp":1670817922000},"page":"454","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Acquired von Willebrand Syndrome Secondary to Normally Functioning Mechanical Aortic Valve and High-Output Cardiac State"],"prefix":"10.3390","volume":"9","author":[{"given":"Xinglin","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3406-5035","authenticated-orcid":false,"given":"Jinghong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Central Clinical School, Monash University, Melbourne, VIC 3004, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yamin","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuemin","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxiao","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhua","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jihai","family":"Liu","sequence":"additional","affiliation":[{"name":"Emergency Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7247-995X","authenticated-orcid":false,"given":"Jiangshan","family":"Wang","sequence":"additional","affiliation":[{"name":"Emergency Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huadong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Emergency Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6777","DOI":"10.1182\/blood-2010-11-297580","article-title":"How I treat the acquired von Willebrand syndrome","volume":"117","author":"Tiede","year":"2011","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1016\/j.jacc.2018.12.045","article-title":"von Willebrand Factor and Management of Heart Valve Disease JACC Review Topic of the Week","volume":"73","author":"Vincent","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.5551\/jat.30809","article-title":"Unexpectedly High Prevalence of Acquired von Willebrand Syndrome in Patients with Severe Aortic Stenosis as Evaluated with a Novel Large Multimer Index","volume":"22","author":"Tamura","year":"2015","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1111\/jth.12734","article-title":"Shear stress-associated acquired von Willebrand syndrome in patients with mitral regurgitation","volume":"12","author":"Blackshear","year":"2014","journal-title":"J. Thromb. Haemost."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/j.jcin.2015.02.008","article-title":"Treatment of Acquired von Willebrand Syndrome in Aortic Stenosis with Transcatheter Aortic Valve Replacement","volume":"8","author":"Spangenberg","year":"2015","journal-title":"JACC Cardiovasc. Interv."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1001\/jamacardio.2016.0075","article-title":"von Willebrand Factor Abnormalities and Heyde Syndrome in Dysfunctional Heart Valve Prostheses","volume":"1","author":"Blackshear","year":"2016","journal-title":"JAMA Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1056\/NEJM195807242590416","article-title":"Gastrointestinal bleeding in aortic stenosis","volume":"259","author":"Heyde","year":"1958","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/0140-6736(92)92434-H","article-title":"Aortic stenosis and bleeding gastrointestinal angiodysplasia: Is acquired von Willebrand\u2019s disease the link?","volume":"340","author":"Warkentin","year":"1992","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1182\/blood-2014-05-378638","article-title":"von Willebrand factor, Jedi knight of the bloodstream","volume":"124","author":"Springer","year":"2014","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1097\/MOH.0000000000000272","article-title":"How much do we really know about von Willebrand disease?","volume":"23","author":"Swystun","year":"2016","journal-title":"Curr. Opin. Hematol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1111\/bjh.13064","article-title":"The diagnosis and management of von Willebrand disease: A United Kingdom Haemophilia Centre Doctors Organization guideline approved by the British Committee for Standards in Haematology","volume":"167","author":"Laffan","year":"2014","journal-title":"Br. J. Haematol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1182\/bloodadvances.2020003265","article-title":"ASH ISTH NHF WFH 2021 guidelines on the diagnosis of von Willebrand disease","volume":"5","author":"James","year":"2021","journal-title":"Blood Adv."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/S0049-3848(99)00196-6","article-title":"A rapid method to visualize von willebrand factor multimers by using agarose gel electrophoresis, immunolocalization and luminographic detection","volume":"97","author":"Krizek","year":"2000","journal-title":"Thromb. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1056\/NEJMoa022831","article-title":"Acquired von Willebrand syndrome in aortic stenosis","volume":"349","author":"Vincentelli","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.amjcard.2012.10.015","article-title":"Indexes of von Willebrand factor as biomarkers of aortic stenosis severity (from the Biomarkers of Aortic Stenosis Severity [BASS] study)","volume":"111","author":"Blackshear","year":"2013","journal-title":"Am. J. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1111\/j.1600-0609.2011.01664.x","article-title":"Acquired von Willebrand syndrome and mitral valve prosthesis leakage. A pilot study","volume":"87","author":"Pinto","year":"2011","journal-title":"Eur. J. Haematol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/j.1540-8191.1995.tb01234.x","article-title":"Evaluation of St. Jude Medical mitral valve function by exercise Doppler echocardiography","volume":"10","author":"Shigenobu","year":"1995","journal-title":"J. Card. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.echo.2009.07.013","article-title":"Recommendations for evaluation of prosthetic valves with echocardiography and doppler ultrasound: A report From the American Society of Echocardiography\u2019s Guidelines and Standards Committee and the Task Force on Prosthetic Valves, developed in conjunction with the American College of Cardiology Cardiovascular Imaging Committee, Cardiac Imaging Committee of the American Heart Association, the European Association of Echocardiography, a registered branch of the European Society of Cardiology, the Japanese Society of Echocardiography and the Canadian Society of Echocardiography, endorsed by the American College of Cardiology Foundation, American Heart Association, European Association of Echocardiography, a registered branch of the European Society of Cardiology, the Japanese Society of Echocardiography, and Canadian Society of Echocardiography","volume":"22","author":"Zoghbi","year":"2009","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.hoc.2021.07.005","article-title":"Acquired von Willebrand Syndrome","volume":"35","author":"Langer","year":"2021","journal-title":"Hematol. Oncol. Clin. N. Am."}],"container-title":["Journal of Cardiovascular Development and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2308-3425\/9\/12\/454\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:39:29Z","timestamp":1760146769000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2308-3425\/9\/12\/454"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,12]]},"references-count":19,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["jcdd9120454"],"URL":"https:\/\/doi.org\/10.3390\/jcdd9120454","relation":{},"ISSN":["2308-3425"],"issn-type":[{"type":"electronic","value":"2308-3425"}],"subject":[],"published":{"date-parts":[[2022,12,12]]}}}