{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T05:03:39Z","timestamp":1768885419729,"version":"3.49.0"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T00:00:00Z","timestamp":1542153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology , Ministry of Science and Technology","doi-asserted-by":"publisher","award":["BT\/PR14423\/MED\/12\/477\/2010"],"award-info":[{"award-number":["BT\/PR14423\/MED\/12\/477\/2010"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Factor replacement therapy in treatment of haemophilia A is complicated by the production of neutralising antibodies known as inhibitors. The formation of inhibitors is multifactorial being associated with both genetic and environmental factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To document the prevalence of inhibitors in severe haemophilia in the community where most patients receive only infrequent episodic replacement therapy and evaluate the factors which could be contributing to it.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Community based camps were conducted in different parts of the country. Patients were assessed through a structured questionnaire and blood samples were obtained for laboratory evaluation of inhibitors and defined immunological parameters.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Inhibitors were present in 87\/447 (19.5%) of the evaluated patients. High\u2010titre inhibitor (&gt;5 Bethesda Units [BU]) was identified in 31 (35.6%) patients. HLA DRB1\u201013\u2010positive cases (RR\u00a0=\u00a02.04; 95% CI 1.06\u20103.911; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.033) had an increased risk of inhibitor formation which was retained in the high\u2010titre subset. A decreased risk of inhibitor formation was noted with heterozygous <jats:italic>IL4\u2010590 C\/T<\/jats:italic> allele (RR\u00a0=\u00a00.22; 95% CI 0.108\u20100.442: <jats:italic>P<\/jats:italic>\u00a0=\u00a00.000). There were no significant correlations between any of the evaluated environmental factors and the development of inhibitors in this study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The overall prevalence of inhibitors in patients with severe haemophilia A is similar to that reported among patients receiving regular replacement therapy. The data from this study, limited by its retrospective and cross\u2010sectional study design, would suggest that genetic rather than environmental are more likely to impact the development of inhibitors.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.13633","type":"journal-article","created":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T13:47:59Z","timestamp":1542203279000},"page":"67-74","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Prevalence of FVIII inhibitors in severe haemophilia A patients: Effect of treatment and genetic factors in an Indian population"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9433-9624","authenticated-orcid":false,"given":"Sachin","family":"David","sequence":"first","affiliation":[{"name":"Department of Haematology Christian Medical College Vellore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sukesh C.","family":"Nair","sequence":"additional","affiliation":[{"name":"Department of Immunohaematology and Transfusion Medicine Christian Medical College Vellore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. Surender","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Immunohaematology and Transfusion Medicine Christian Medical College Vellore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ansu Abu","family":"Alex","sequence":"additional","affiliation":[{"name":"Department of Haematology Christian Medical College Vellore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saravanan","family":"Ganesan","sequence":"additional","affiliation":[{"name":"Department of Haematology Christian Medical College Vellore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamenth Kumar","family":"Palani","sequence":"additional","affiliation":[{"name":"Department of Haematology Christian Medical College Vellore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nithya","family":"Balasundaram","sequence":"additional","affiliation":[{"name":"Department of Haematology Christian Medical College Vellore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kavitha M.","family":"Lakshmi","sequence":"additional","affiliation":[{"name":"Department of Haematology Christian Medical College Vellore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aditi","family":"Joshi","sequence":"additional","affiliation":[{"name":"Sahyadri Speciality Hospital Pune India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Kannan","sequence":"additional","affiliation":[{"name":"Sahyadri Speciality Hospital Pune India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anu","family":"Korula","sequence":"additional","affiliation":[{"name":"Department of Haematology Christian Medical College Vellore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fouzia","family":"Nambiatheyil Aboobacker","sequence":"additional","affiliation":[{"name":"Department of Haematology Christian Medical College Vellore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aby","family":"Abraham","sequence":"additional","affiliation":[{"name":"Department of Haematology Christian Medical College Vellore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biju","family":"George","sequence":"additional","affiliation":[{"name":"Department of Haematology Christian Medical College Vellore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shashikant Janardan","family":"Apte","sequence":"additional","affiliation":[{"name":"Sahyadri Speciality Hospital Pune India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5032-5020","authenticated-orcid":false,"given":"Alok","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Haematology Christian Medical College Vellore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9417-2353","authenticated-orcid":false,"given":"Vikram","family":"Mathews","sequence":"additional","affiliation":[{"name":"Department of Haematology Christian Medical College Vellore India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,11,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1617"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-07-444877"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12412"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa075760"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830420408"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/MBC.0000000000000377"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.12495"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2516.2001.00510.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2009.02197.x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1245105"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2008.01694.x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12168"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2007.02290.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-09-3918"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03636.x"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2516.2003.00780.x"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12288-014-0342-z"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2005.01121.x"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2004.046490"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-06-026104"},{"key":"e_1_2_8_22_1","unstructured":"https:\/\/www1.wfh.org\/publication\/files\/pdf-1669.pdf. Accessed February 21 2018."},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12288-015-0562-x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12687-011-0072-y"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1245115"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1516437"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2009.02131.x"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2011.02739.x"},{"issue":"9","key":"e_1_2_8_29_1","first-page":"2428","article-title":"A multicenter study of recombinant factor VIII (recombinate): safety, efficacy, and inhibitor risk in previously untreated patients with hemophilia A. The Recombinate Study Group","volume":"83","author":"Bray GL","year":"1994","journal-title":"Blood"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2001.02828.x"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2006.01418.x"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1177\/2040620712464509"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1208024"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-07-586347"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.17.1.701"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.173.3.747"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2004.00802.x"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.19.6149"},{"issue":"5","key":"e_1_2_8_39_1","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1210\/jcem.85.5.6588","article-title":"Cytokine gene polymorphisms in autoimmune thyroid disease","volume":"85","author":"Hunt PJ","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2012.02845.x"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/tan.12364"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1140"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1166"},{"key":"e_1_2_8_44_1","article-title":"Factor VIII haplotypes in severe hemophilia A patients in India","author":"Pinto P","year":"2012","journal-title":"Ann Hematol"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12004"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-09-599365"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhae.13633","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.13633","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T04:19:58Z","timestamp":1694665198000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.13633"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,14]]},"references-count":45,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,1]]}},"alternative-id":["10.1111\/hae.13633"],"URL":"https:\/\/doi.org\/10.1111\/hae.13633","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,14]]},"assertion":[{"value":"2018-07-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}