{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:34:36Z","timestamp":1791513276112,"version":"4.3.4"},"reference-count":28,"publisher":"American Society of Hematology","issue":"13","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,7,14]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Low von Willebrand factor (VWF) in adults is associated with significant bleeding, most notably heavy menstrual bleeding (HMB) and postpartum hemorrhage, although this has not been characterized in adolescents. The objectives of this analysis of a multicenter single arm observational cohort study in adolescents with low VWF\u2013associated HMB were to describe the bleeding phenotype, HMB severity, and related complications. Eligibility criteria included postmenarchal females &amp;lt;21 years of age with HMB (Pictorial Blood Assessment Chart [PBAC] score &amp;gt;100) and low VWF (2 values of VWF activity \u226530 and \u226450 IU\/dL). Patients diagnosed with other bleeding disorders were ineligible. Clinical phenotype data, including PBAC and Bleeding Assessment Tool (BAT) scores, laboratory data, and HMB management\/outcome details, were extracted. Patient demographics and clinical characteristics were summarized as medians with minimum\/maximum values or frequencies with percentages. Groups were compared using a Wilcoxon rank-sum test or Fisher\u2019s exact test. A total of 113 patients met inclusion criteria, and 2 were excluded. Ninety four percent had a significant bleeding phenotype (BAT score &amp;gt;2), with predominantly mucocutaneous bleeding (32%-44%), postprocedural\/surgical bleeding (15%), and severe HMB (BAT HMB domain score \u22652; 90%). Bleeding complications included iron deficiency (60%), anemia (21%), transfusion (12%), and hospitalization (10%). Desmopressin challenge response in subjects tested was good and sustained. Several (48%) required combined therapy for HMB (hormonal\/hemostatic), and one third did not show improvement despite therapy. Our results suggest that adolescent females with low VWF have a significant bleeding phenotype and resultant complications warranting a focus on prompt diagnosis, appropriate therapy, and prevention of complications.<\/jats:p>","DOI":"10.1182\/bloodadvances.2020002081","type":"journal-article","created":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T23:33:38Z","timestamp":1594942418000},"page":"3209-3216","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":25,"title":["The spectrum and severity of bleeding in adolescents with low von Willebrand factor\u2013associated heavy menstrual bleeding"],"prefix":"10.1182","volume":"4","author":[{"given":"Lakshmi","family":"Srivaths","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4631-6943","authenticated-orcid":false,"given":"Charles G.","family":"Minard","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8855-9746","authenticated-orcid":false,"given":"Sarah H.","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology, Nationwide Children\u2019s Hospital, Columbus, OH;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison P.","family":"Wheeler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Vanderbilt University Medical Center, Vanderbilt, TN;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1544-9068","authenticated-orcid":false,"given":"Eric","family":"Mullins","sequence":"additional","affiliation":[{"name":"Division of Hematology, University of Cincinnati College of Medicine and Cincinnati Children\u2019s Hospital, Cincinnati, OH;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukta","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Mercy Hospital, Kansas City, MO;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Sidonio","sequence":"additional","affiliation":[{"name":"Aflac Cancer and Blood Disorders Center, Emory University, Atlanta, GA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5523-1939","authenticated-orcid":false,"given":"Shilpa","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Buffalo, Buffalo, NY;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3283-0415","authenticated-orcid":false,"given":"Ayesha","family":"Zia","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The University of Texas, Southwestern, Dallas, TX;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret V.","family":"Ragni","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, University of Pittsburgh, Pittsburgh, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshni","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development, Michigan State University, East Lansing, MI;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer E.","family":"Dietrich","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX;"},{"name":"Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3857-8313","authenticated-orcid":false,"given":"Peter A.","family":"Kouides","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Rochester, Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2020,7,14]]},"reference":[{"key":"2021032618462933000_B1","article-title":"Diagnosis and management of heavy menstrual bleeding and bleeding disorders in adolescents [published online ahead of print 30 December 2019]","author":"Borzutzky","journal-title":"JAMA Pediatr"},{"issue":"2","key":"2021032618462933000_B2","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.jpag.2012.07.001","article-title":"Gynecologic concerns in pubertal females with blood disorders","volume":"26","author":"Venkateswaran","year":"2013","journal-title":"J Pediatr Adolesc Gynecol"},{"issue":"3","key":"2021032618462933000_B3","doi-asserted-by":"crossref","first-page":"e71","DOI":"10.1097\/AOG.0000000000003411","article-title":"Screening and management of bleeding disorders in adolescents with heavy menstrual bleeding: ACOG Committee Opinion, Number 785","volume":"134","year":"2019","journal-title":"Obstet Gynecol"},{"issue":"1","key":"2021032618462933000_B4","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/hae.13330","article-title":"Differences in bleeding phenotype and provider interventions in postmenarchal adolescents when compared to adult women with bleeding disorders and heavy menstrual bleeding","volume":"24","author":"Srivaths","year":"2018","journal-title":"Haemophilia"},{"key":"2021032618462933000_B5","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1182\/asheducation-2009.1.106","article-title":"Low von Willebrand factor: sometimes a risk factor and sometimes a disease","volume":"2009","author":"Sadler","year":"2009","journal-title":"Hematology Am Soc Hematol Educ Program"},{"issue":"8","key":"2021032618462933000_B6","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1182\/blood-2018-10-844936","article-title":"How I treat low von Willebrand factor levels","volume":"133","author":"Lavin","year":"2019","journal-title":"Blood"},{"issue":"21","key":"2021032618462933000_B7","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1182\/blood-2017-05-786699","article-title":"Novel insights into the clinical phenotype and pathophysiology underlying low VWF levels","volume":"130","author":"Lavin","year":"2017","journal-title":"Blood"},{"issue":"14","key":"2021032618462933000_B8","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1182\/bloodadvances.2018017418","article-title":"Significant gynecological bleeding in women with low von Willebrand factor levels","volume":"2","author":"Lavin","year":"2018","journal-title":"Blood Adv"},{"issue":"6","key":"2021032618462933000_B9","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.jpag.2013.12.011","article-title":"Hemostatic abnormalities in young females with heavy menstrual bleeding","volume":"27","author":"D\u00edaz","year":"2014","journal-title":"J Pediatr Adolesc Gynecol"},{"issue":"6","key":"2021032618462933000_B10","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1097\/AOG.0000000000002620","article-title":"Patterns of von Willebrand disease screening in girls and adolescents with heavy menstrual bleeding","volume":"131","author":"Jacobson","year":"2018","journal-title":"Obstet Gynecol"},{"issue":"1","key":"2021032618462933000_B11","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1182\/bloodadvances.2019000992","article-title":"Low VWF levels in children and lack of association with bleeding in children undergoing tonsillectomy","volume":"4","author":"Gill","year":"2020","journal-title":"Blood Adv"},{"issue":"suppl 1","key":"2021032618462933000_B12","doi-asserted-by":"crossref","first-page":"Abstract 2414","DOI":"10.1182\/blood-2019-123734","article-title":"Diagnostic and therapeutic decision making in pediatric patients with low von Willebrand factor","volume":"134","author":"Shui","year":"2019","journal-title":"Blood"},{"issue":"suppl 1","key":"2021032618462933000_B13","doi-asserted-by":"crossref","first-page":"Abstract 2400","DOI":"10.1182\/blood-2019-130023","article-title":"Perioperative bleeding risk assessment in a cohort of children with low levels of von Willebrand factor","volume":"134","author":"Pollio","year":"2019","journal-title":"Blood"},{"issue":"5","key":"2021032618462933000_B14","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1097\/GCO.0000000000000394","article-title":"Evaluation and management of heavy menstrual bleeding in adolescents","volume":"29","author":"Moon","year":"2017","journal-title":"Curr Opin Obstet Gynecol"},{"issue":"4","key":"2021032618462933000_B15","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1159\/000320336","article-title":"Pictorial blood loss assessment chart in the evaluation of heavy menstrual bleeding: diagnostic accuracy compared to alkaline hematin","volume":"71","author":"Zakherah","year":"2011","journal-title":"Gynecol Obstet Invest"},{"issue":"6","key":"2021032618462933000_B16","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1111\/hae.12503","article-title":"Normal range of bleeding scores for the ISTH-BAT: adult and pediatric data from The Merging Project","volume":"20","author":"Elbatarny","year":"2014","journal-title":"Haemophilia"},{"issue":"2","key":"2021032618462933000_B17","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/bjh.15565","article-title":"von Willebrand factor clearance - biological mechanisms and clinical significance","volume":"183","author":"O\u2019Sullivan","year":"2018","journal-title":"Br J Haematol"},{"issue":"14","key":"2021032618462933000_B18","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1182\/blood-2018-09-874636","article-title":"Increased galactose expression and enhanced clearance in patients with low von Willebrand factor","volume":"133","author":"Aguila","year":"2019","journal-title":"Blood"},{"issue":"12","key":"2021032618462933000_B19","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1182\/blood-2012-09-455089","article-title":"VWF propeptide and ratios between VWF, VWF propeptide, and FVIII in the characterization of type 1 von Willebrand disease","volume":"121","author":"Eikenboom","year":"2013","journal-title":"Blood"},{"key":"2021032618462933000_B20","doi-asserted-by":"crossref","first-page":"4147","DOI":"10.1182\/bloodadvances.2019000863","article-title":"von Willebrand factor and factor VIII levels after desmopressin are associated with the bleeding phenotype in type 1 VWD","volume":"3","author":"Atiq","year":"2019","journal-title":"Blood Adv"},{"issue":"6","key":"2021032618462933000_B21","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1111\/bjh.13331","article-title":"The utility of the DDAVP challenge test in children with low von Willebrand factor","volume":"170","author":"Archer","year":"2015","journal-title":"Br J Haematol"},{"issue":"7","key":"2021032618462933000_B22","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.3324\/haematol.2019.225656","article-title":"Bleeding disorders in adolescents with heavy menstrual bleeding in a multicentre prospective US cohort","volume":"105","author":"Zia","year":"2020","journal-title":"Haematologica"},{"issue":"2","key":"2021032618462933000_B23","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/hae.12046","article-title":"Iron deficiency and fatigue in adolescent females with heavy menstrual bleeding","volume":"19","author":"Wang","year":"2013","journal-title":"Haemophilia"},{"issue":"11","key":"2021032618462933000_B24","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.3945\/jn.117.255356","article-title":"Consumption of iron-biofortified beans positively affects cognitive performance in 18- to 27-year-old Rwandan female college students in an 18-week randomized controlled efficacy trial","volume":"147","author":"Murray-Kolb","year":"2017","journal-title":"J Nutr"},{"issue":"6","key":"2021032618462933000_B25","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1542\/peds.107.6.1381","article-title":"Iron deficiency and cognitive achievement among school-aged children and adolescents in the United States","volume":"107","author":"Halterman","year":"2001","journal-title":"Pediatrics"},{"issue":"7","key":"2021032618462933000_B26","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1111\/pcn.12656","article-title":"Association between iron-deficiency anemia and depression: a web-based Japanese investigation","volume":"72","author":"Hidese","year":"2018","journal-title":"Psychiatry Clin Neurosci"},{"issue":"1","key":"2021032618462933000_B27","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1080\/03007995.2017.1394833","article-title":"Iron deficiency beyond erythropoiesis: should we be concerned?","volume":"34","author":"Musallam","year":"2018","journal-title":"Curr Med Res Opin"},{"key":"2021032618462933000_B28","unstructured":"American Society of Hematology . Public Comment on Guidelines on the Diagnosis and Management of von Willebrand Disease. Available at: https:\/\/hematology.org\/education\/clinicians\/guidelines-and-quality-care\/public-comment-guidelines\/public-comment-on-guidelines-on-the-diagnosis-and-management-of-von-willebrand-disease. Accessed 24 June 2020."}],"updated-by":[{"DOI":"10.1182\/bloodadvances.2021004671","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T00:00:00Z","timestamp":1617667200000}}],"container-title":["Blood Advances"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/bloodadvances\/article-pdf\/4\/13\/3209\/1804071\/advancesadv2020002081.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/bloodadvances\/article-pdf\/4\/13\/3209\/1804071\/advancesadv2020002081.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T09:54:06Z","timestamp":1696413246000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/bloodadvances\/article\/4\/13\/3209\/461318\/The-spectrum-and-severity-of-bleeding-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,14]]},"references-count":28,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2020,7,14]]}},"URL":"https:\/\/doi.org\/10.1182\/bloodadvances.2020002081","relation":{"erratum":[{"id-type":"doi","id":"10.1182\/bloodadvances.2021004671","asserted-by":"object"}]},"ISSN":["2473-9529","2473-9537"],"issn-type":[{"value":"2473-9529","type":"print"},{"value":"2473-9537","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,14]]}}}