{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T11:15:08Z","timestamp":1781954108723,"version":"3.54.5"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T00:00:00Z","timestamp":1734566400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008322","name":"CSL Behring","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Maintaining the balance between procoagulant and anticoagulant factors is essential for effective haemostasis. Emerging evidence suggests a modulation of bleeding tendency by factors in the anticoagulant and fibrinolytic systems.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>This study investigates the clinical and laboratory characteristics of a family with combined von Willebrand disease (VWD) and antithrombin (AT) deficiency.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study focused on a 38\u2010year\u2010old female index patient (IP) with severe type 3 VWD and a history of bleeding disorders. Coagulation assays included VWF antigen, platelet\u2010dependent VWF activity, factor VIII activity, thrombin generation assay (TGA) and AT activity. Molecular genetic analyses were conducted by a targeted DNA custom next generation sequencing (NGS) panel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The IP and one of her sisters suffered type 3 VWD. While the IP presents with a classical severe bleeding phenotype, the sister (II\u20102) exhibited less severe bleeding symptoms. Extended family members showed type 1 VWD with mild presentations. NGS revealed a homozygous deletion of exon 6 in the <jats:italic>VWF<\/jats:italic> gene in the IP and her sister (II\u20102). All other family members carry this genetic variant in a heterozygous state. Additionally, II\u20102 has a heterozygous variant in the <jats:italic>SERPINC1<\/jats:italic> gene (c.133C&gt;T, p.Arg45Trp). Both IP and II\u20102 carry a homozygous prothrombin G20210A variant. TGA results indicated reduced thrombin generation in severe VWD patients, with a pronounced thrombin burst in those with the AT and prothrombin G20210A variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>AT deficiency appears to modulate bleeding symptoms in severe VWD. This study emphasizes the importance of comprehensive genetic and phenotypic evaluation in managing complex coagulation disorders.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.15147","type":"journal-article","created":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T12:31:13Z","timestamp":1734611473000},"page":"140-147","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Modulation of Haemostatic Balance in Combined von Willebrand Disease and Antithrombin Deficiency: A Comprehensive Family Study"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4796-3424","authenticated-orcid":false,"given":"Behnaz","family":"Pezeshkpoor","sequence":"first","affiliation":[{"name":"Institute of Experimental Hematology and Transfusion Medicine Medical Faculty University Hospital Bonn University of Bonn  Bonn 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