{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:12:00Z","timestamp":1747185120400,"version":"3.40.5"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T00:00:00Z","timestamp":1723075200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004411","name":"Heart and Stroke Foundation of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Congenital factor V (FV) deficiency is a rare clotting disorder affecting \u223c1 in 1,000,000, with bleeding severity that ranges broadly for poorly understood reasons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To help understand the molecular basis of the observed phenotype in FV deficient patients, the genetics and biochemistry causing a patient's FV deficiency were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>A 71\u2010year\u2010old female, who had serious life\u2010long bleeding upon provocation and profound menorrhagia that lead to hysterectomy, was found to have 3% of normal plasma FV antigen with normal electrophoretic mobility. Platelet FV was similarly low, although the banding pattern was less fragmented than normal. Plasma clotting activity was &lt;1% of normal. Familial inheritance and DNA sequence analysis from peripheral blood leukocytes were consistent with novel compound heterozygosity with missense mutations in exon XVII, Leu1821 to Ser (L1821S) and exon XXV, Gly2192 to Cys (G2192C). The respective single\u2010mutation variants were expressed and purified. Explaining why the antigen level and activity were inequivalent, thrombin activation of recombinant (<jats:italic>r<\/jats:italic>) FV\/L1821S was impaired, and rFV\/G2192C was unable to bind to a procoagulant phospholipid membrane.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings are consistent with the observed phenotype, highlighting the importance of understanding FV biochemical function to rationalize clinical bleeding severity when the circulating antigen level is discordant.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.15087","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T05:00:23Z","timestamp":1723179623000},"page":"1170-1176","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Factor V haemostatic diathesis impairing thrombin activation, membrane binding and circulating antigen level due to a novel compound heterozygous mutation, Leu1821Ser and Gly2192Cys"],"prefix":"10.1111","volume":"30","author":[{"given":"Kimberley","family":"Talbot","sequence":"first","affiliation":[{"name":"Canadian Blood Services, Medical Affairs and Innovation  Vancouver Canada"},{"name":"University of British Columbia (UBC), Centre for Blood Research  Vancouver Canada"},{"name":"Department of Pathology and Laboratory Medicine UBC  Vancouver Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jina","family":"Song","sequence":"additional","affiliation":[{"name":"Canadian Blood Services, Medical Affairs and Innovation  Vancouver Canada"},{"name":"University of British Columbia (UBC), Centre for Blood Research  Vancouver Canada"},{"name":"Department of Pathology and Laboratory Medicine UBC  Vancouver Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John R.","family":"Perrier","sequence":"additional","affiliation":[{"name":"Canadian Blood Services, Medical Affairs and Innovation  Vancouver Canada"},{"name":"University of British Columbia (UBC), Centre for Blood Research  Vancouver Canada"},{"name":"Department of Pathology and Laboratory Medicine UBC  Vancouver Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shannon","family":"Jackson","sequence":"additional","affiliation":[{"name":"Hematology St. Paul's Hospital, Providence Health Care  Vancouver Canada"},{"name":"Department of Medicine UBC  Vancouver Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ross T. A.","family":"MacGillivray","sequence":"additional","affiliation":[{"name":"University of British Columbia (UBC), Centre for Blood Research  Vancouver Canada"},{"name":"Department of Biochemistry and Molecular Biology UBC  Vancouver Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9170-7586","authenticated-orcid":false,"given":"Edward L. G.","family":"Pryzdial","sequence":"additional","affiliation":[{"name":"Canadian Blood Services, Medical Affairs and Innovation  Vancouver Canada"},{"name":"University of British Columbia (UBC), Centre for Blood Research  Vancouver Canada"},{"name":"Department of Pathology and Laboratory Medicine UBC  Vancouver Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,8,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.232587"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12217"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)68999-9"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-005-4527-3"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/384066a0"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2010.08336.x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-08-237719"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-06-162453"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M402107200"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20090405"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj20031205"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi002209v"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V69.4.1188.1188"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2010.02330.x"},{"key":"e_1_2_11_16_1","unstructured":"European Association for Haemophilia and Allied Disorders (2023) Coagulation Factor V Variant Database.https:\/\/f5\u2010db.eahad.org\/"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M400727200"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)94045-7"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)60624-6"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2009.07708.x"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.14.8537"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019002867"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)44879-4"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021010684"},{"key":"e_1_2_11_25_1","first-page":"193","article-title":"Assembly of viruses: enveloped particles","volume":"151","author":"Navaratnarajah CK","year":"2008","journal-title":"Arch Virol"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19020541"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90532-4"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.24.110707.175333"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-01-408245"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-10-315309"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403072101"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.22.6934"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022015807"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.15087","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T10:40:57Z","timestamp":1746787257000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.15087"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,8]]},"references-count":32,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1111\/hae.15087"],"URL":"https:\/\/doi.org\/10.1111\/hae.15087","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"type":"print","value":"1351-8216"},{"type":"electronic","value":"1365-2516"}],"subject":[],"published":{"date-parts":[[2024,8,8]]},"assertion":[{"value":"2024-06-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}