{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T21:32:36Z","timestamp":1785879156429,"version":"3.56.0"},"reference-count":30,"publisher":"Croatian Society for Medical Biochemistry and Laboratory Medicine","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biochem. med. (Online)"],"published-print":{"date-parts":[[2022,2,15]]},"abstract":"<jats:p>This study reevaluated von Willebrand disease (vWD) diagnosis in a Croatian paediatric cohort by combining bleeding scores (BS), phenotypic laboratory testing, and next-generation sequencing (NGS).\nA total of 25 children (11 males and 14 females, median age 10 years, from 2 to 17) previously diagnosed with vWD were included. BS were calculated using an online bleeding assessment tool. Phenotypic laboratory analyses included platelet count, platelet function analyser closure times, prothrombin time, activated partial thromboplastin time, von Willebrand factor antigen (vWF:Ag), vWF gain-of-function mutant glycoprotein Ib binding activity (vWF:GPIbM), vWF collagen binding activity (vWF:CBA), factor VIII activity (FVIII:C) and multimeric analysis. Next-generation sequencing covered regions of both vWF and FVIII genes and was performed on MiSeq (Illumina, San Diego, USA).\nDisease-associated variants identified in 15 patients comprised 11 distinct heterozygous vWF gene variants in 13 patients and one novel FVIII gene variant (p.Glu2085Lys) in two male siblings. Four vWF variants were novel (p.Gln499Pro, p.Asp1277Tyr, p.Asp1277His, p.Lys1491Glu). Three patients without distinctive variants had vWF:GPIbM between 30 and 50%. Patients with identified vWF gene variants had statistically significant lower values of vWF:GPIbM (P = 0.002), vWF:Ag (P = 0.007), vWF:CBA (P &lt; 0.001) and FVIII:C (P = 0.002), compared to those without. Correlations between BS and phenotypic laboratory test results were not statistically significant for either of the tests.\nThe applied diagnostic approach confirmed the diagnosis of vWD in 13 patients and mild haemophilia A in two. Limited utility of BS in the paediatric population was evidenced.<\/jats:p>","DOI":"10.11613\/bm.2022.010707","type":"journal-article","created":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T07:20:18Z","timestamp":1644564018000},"page":"85-97","source":"Crossref","is-referenced-by-count":2,"title":["Reevaluation of von Willebrand disease diagnosis in a Croatian paediatric cohort combining bleeding scores, phenotypic laboratory assays and next generation sequencing"],"prefix":"10.11613","volume":"32","author":[{"given":"Renata","family":"Zadro","sequence":"first","affiliation":[{"name":"Medical Biochemistry Laboratory, St Catherine Specialty Hospital, Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dunja","family":"Rogi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9sir\u00e9e","family":"Coen-Herak","sequence":"additional","affiliation":[{"name":"Department of Laboratory Diagnostics,University Hospital Center Zagreb, Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernest","family":"Bili\u0107","sequence":"additional","affiliation":[{"name":"Referral Center for Pediatrics Hematology and Oncology, Department of Pediatrics, University Hospital Center Zagreb, Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Dejanovi\u0107 Beki\u0107","sequence":"additional","affiliation":[{"name":"Referral Center for Pediatrics Hematology and Oncology, Department of Pediatrics, University Hospital Center Zagreb, Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margareta","family":"Radi\u0107 Antolic","sequence":"additional","affiliation":[{"name":"Department of Laboratory Diagnostics,University Hospital Center Zagreb, Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Lapi\u0107","sequence":"additional","affiliation":[{"name":"Department of Laboratory Diagnostics,University Hospital Center Zagreb, Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4885","reference":[{"key":"key20220211022014_r1","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1111\/j.1538-7836.2006.02146.x","article-title":"Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.","volume":"4","author":"Sadler","year":"2006","journal-title":"J Thromb Haemost"},{"key":"key20220211022014_r2","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 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tonsillectomy.","volume":"4","author":"Gill","year":"2020","journal-title":"Blood Adv"},{"key":"key20220211022014_r12","first-page":"535","article-title":"Diagnosis and care of patients with mild haemophilia: practical recommendations for clinical management.","volume":"16","author":"Benson","year":"2018","journal-title":"Blood Transfus"},{"key":"key20220211022014_r13","unstructured":"Let\u2019s talk period self-bleeding assessment tool. Available from: https:\/\/letstalkperiod.ca\/self-bat. Accessed October 12th 2021."},{"key":"key20220211022014_r14","doi-asserted-by":"crossref","first-page":"e384","DOI":"10.1111\/hae.12747","article-title":"Generation and optimization of the self-administered bleeding assessment tool and its validation as a screening test for von Willebrand disease.","volume":"21","author":"Deforest","year":"2015","journal-title":"Haemophilia"},{"key":"key20220211022014_r15","doi-asserted-by":"crossref","first-page":"e282","DOI":"10.1111\/hae.13271","article-title":"Let\u2019s Talk Period! Preliminary results of an online bleeding awareness knowledge translation project and bleeding assessment tool promoted on social media.","volume":"23","author":"Reynen","year":"2017","journal-title":"Haemophilia"},{"key":"key20220211022014_r16","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1002\/ajh.25393","article-title":"Automated assays for von Willebrand factor activity.","volume":"94","author":"Higgins","year":"2019","journal-title":"Am J Hematol"},{"key":"key20220211022014_r17","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1002\/rth2.12141","article-title":"Evaluation of a semi-automated von Willebrand factor multimer assay, the Hydragel 5 von Willebrand multimer, by two European Centers.","volume":"2","author":"Bowyer","year":"2018","journal-title":"Res Pract Thromb Haemost"},{"key":"key20220211022014_r18"},{"key":"key20220211022014_r19"},{"key":"key20220211022014_r20","unstructured":"Von Willebrand factor Variant Database [database online]. Available from: http:\/\/www.vWF.group.shef.ac.uk\/, Accessed June 10th 2021."},{"key":"key20220211022014_r21","unstructured":"EAHAD FVIII Gene Variant Database [database online]. Available from: https:\/\/f8-db.eahad.org\/ Accessed June 10th 2021."},{"key":"key20220211022014_r22","unstructured":"VarSome. The human genetics search engine. Available from: https:\/\/varsome.com. 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