{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T23:55:43Z","timestamp":1772841343912,"version":"3.50.1"},"reference-count":22,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,3,23]],"date-time":"2024-03-23T00:00:00Z","timestamp":1711152000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp;amp; Cancer"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Thrombin is a critical protease modulating thrombosis as well as inflammation, which are one of the main pathophysiological mechanisms in sickle vasculopathy, and its levels were reported to be high in sickle cell disease (SCD). The thrombin\u2013thrombomodulin complex activates the TAFI inhibitor of fibrinolysis, which acts by reducing plasmin affinity for its substrate thus hindering fibrinolysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We aimed to determine the influence of the Thr325Ile single nucleotide polymorphism (SNP) on TAFI antigen levels and potential effects on the severity of SCD in a cohort of Egyptian patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Genotyping of Thr325lle polymorphism using Taq\u2010Man SNP genotyping assay and TAFI level measurement using an enzyme\u2010linked immunosorbent assay were performed for 80 SCD patients (45 homozygous HbSS, 16 S\/\u03b2<jats:sup>0<\/jats:sup> and 19 S\u03b2<jats:sup>+<\/jats:sup>) as well as 80 age\u2010 and gender\u2010matched healthy control subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Plasma TAFI levels were higher in SCD patients with Thr325Ile polymorphism, yet the difference was not statistically significant (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.204). SCD patients with polymorphic genotypes had a greater number of hospital admissions (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.03). Ten patients with acute chest syndrome had the homozygous polymorphic genotype (GG), and all patients with pulmonary hypertension had the polymorphic genotype (six were homozygous [GG] and five were heterozygous [GA]). Patients with SCD complicated with pulmonary hypertension showed significantly higher plasma TAFI levels (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.044).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The analysis of Thr325Ile polymorphisms combined with plasma TAFI levels suggests that the analyzed SNP could influence plasma TAFL levels and SCD disease severity and hospitalization rates, which could be predictors for complex disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.30959","type":"journal-article","created":{"date-parts":[[2024,3,23]],"date-time":"2024-03-23T12:44:55Z","timestamp":1711197895000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Thrombin activatable fibrinolysis inhibitor plasma levels and <i>TAFI<\/i> Thr325Ile genetic polymorphism in a cohort of Egyptian sickle cell disease patients and impact on disease severity"],"prefix":"10.1002","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1783-6133","authenticated-orcid":false,"given":"Mona","family":"Hamdy","sequence":"first","affiliation":[{"name":"Department of Pediatrics Pediatric Hematology and BMT Unit Faculty of Medicine Cairo University  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iman A.","family":"Shaheen","sequence":"additional","affiliation":[{"name":"Department of Clinical and Chemical Pathology Faculty of Medicine Cairo University  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed","family":"Khallaf","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Pediatric Hematology and BMT Unit Faculty of Medicine Cairo University  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6423-7782","authenticated-orcid":false,"given":"Yasmeen M. M.","family":"Selim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Pediatric Hematology and BMT Unit Faculty of Medicine Cairo University  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,3,23]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.239343"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.11763"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000193"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890600852898"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M104444200"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.42.27176"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1615394"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.6.1992"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.45.10.902"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.2147\/CEOR.S276121"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.3109\/08880011003739448"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22073670"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mgene.2015.03.004"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2003.04549.x"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/AC.66.4.2126597"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.239350"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1089\/ped.2017.0814"},{"key":"e_1_2_12_19_1","volume-title":"Conn's current therapy 2016","author":"Bope ET","year":"2015"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201105-0783OC"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14655"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200610-1498OC"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.310640"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.30959","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T13:07:54Z","timestamp":1753448874000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.30959"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,23]]},"references-count":22,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1002\/pbc.30959"],"URL":"https:\/\/doi.org\/10.1002\/pbc.30959","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,23]]},"assertion":[{"value":"2023-11-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e30959"}}