{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T03:40:13Z","timestamp":1704426013882},"reference-count":36,"publisher":"Wiley","issue":"s6","license":[{"start":{"date-parts":[[2006,11,10]],"date-time":"2006-11-10T00:00:00Z","timestamp":1163116800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2006,12]]},"abstract":"<jats:p><jats:bold>Summary.\u2002<\/jats:bold> Although up to 80% of high\u2010responding inhibitors in patients with severe factor VIII deficiency can be eliminated using heterogeneous regimens for immune tolerance induction, the residual morbidity in this population of haemophilic patients is far from trivial. There is an exigent need for focussed basic, translational and clinical research to extend our understanding of the pathogenesis of haemophilic inhibitor development. In this article, we identify four key research needs, including (i) whether presently available clotting factor concentrates (CFCs) have differential antigenicity, giving rise to clinically relevant immunogenicity; (ii) the interplay of quantitative and qualitative (e.g. age at first exposure) influences of CFCs as well as host\u2013environmental factors (e.g. vaccination effects) on inhibitor development; (iii) the therapeutic role (if any) that concurrent immune tolerance with suppressive or immune\u2010competitive therapeutic strategies play in inhibitor eradication and (iv) pending any major therapeutic advances, alternative or enhanced strategies for treating acute haemorrhage and for preventing chronic haemorrhagic events in these patients.<\/jats:p>","DOI":"10.1111\/j.1365-2516.2006.01374.x","type":"journal-article","created":{"date-parts":[[2006,11,10]],"date-time":"2006-11-10T14:06:14Z","timestamp":1163167574000},"page":"107-113","source":"Crossref","is-referenced-by-count":6,"title":["Urgent inhibitor issues: targets for expanded research"],"prefix":"10.1111","volume":"12","author":[{"given":"W. K.","family":"HOOTS","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,11,10]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2005.01375.x"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1649954"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/9780470987124.ch9"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1651565"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1655911"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-04-1371"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.mbc.0000167660.30886.e9"},{"key":"e_1_2_7_9_2","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1055\/s-0037-1613191","article-title":"Von Willebrand factor modulates factor VIII immunogenicity: comparative study of different factor VIII concentrates in a haemophilia A mouse model","volume":"88","author":"Behrman M","year":"2002","journal-title":"Thromb Haemost"},{"key":"e_1_2_7_10_2","first-page":"EREP03","article-title":"Variation in factor VIII inhibitor reactivity with different commercial factor VIII preparations: is it of clinical importance","volume":"88","author":"Berntorp E","year":"2003","journal-title":"Haematologica"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2257.1988.tb01191.x"},{"key":"e_1_2_7_12_2","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1182\/blood.V66.4.973.973","article-title":"A longitudinal study of patients with hemophilia: immunologic correlates of infection with HTLV\u2010111\/LAV and other viruses","volume":"66","author":"Stein SF","year":"1985","journal-title":"Blood"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2006.01200.x"},{"key":"e_1_2_7_14_2","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1160\/TH04-08-0485","article-title":"Factor VIII efficient and specific non\u2010covalent binding to PEGylated liposomes enables prolongation of its circulation time and haemostatic efficacy","volume":"93","author":"Baru M","year":"2005","journal-title":"Thromb Haemost"},{"key":"e_1_2_7_15_2","first-page":"59","article-title":"Polysialylation: the natural way to improve the stability and pharmacokinetics of protein and peptide drugs","volume":"4","author":"Jain S","year":"2005","journal-title":"Drug Deliv Syst Sci"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.10.3311"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2516.2000.00451.x"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1423-0410.2001.00007.x"},{"key":"e_1_2_7_19_2","doi-asserted-by":"crossref","unstructured":"PuleyandaRK VelanderWH LeeTKet\u00a0al.Transgenic pigs produce functional human VIII in milk.Nat Biotechnol1997;15:971\u20135.","DOI":"10.1038\/nbt1097-971"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2004.00983.x"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-11-3891"},{"key":"e_1_2_7_22_2","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1055\/s-0038-1650216","article-title":"Safety profile of porcine factor VIII and its use as hospital and home therapy for patients with haemophilia\u2010A and inhibitors: the results of an international survey","volume":"75","author":"Hay CR","year":"1996","journal-title":"Thromb Haemost"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/9780470987124.ch11"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1423-0410.1996.tb01346.x"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1159\/000056710"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1612943"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198804143181503"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-03-0765"},{"issue":"10","key":"e_1_2_7_29_2","first-page":"35","article-title":"Inhibition of CD40 ligand (CD154) in the treatment of factor VIII inhibitors","volume":"85","author":"Ewenstein BM","year":"2000","journal-title":"Haematologica"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1616733"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/9780470987124.ch14"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.2165\/00063030-200013040-00007"},{"issue":"1","key":"e_1_2_7_33_2","article-title":"Cross\u2010over comparative study of tolerability, pharmacokinetics and efficacy of porcine factor VIII in the canine model of hemophilia A","volume":"3","author":"Bergman G","year":"2005","journal-title":"J Thromb Haemost"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1538-7836.2003.00444.x"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH05-05-0361"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-07-2733"},{"issue":"1","key":"e_1_2_7_37_2","article-title":"Anti\u2010idiotypic monoclonal antibodies (anti\u2010Id mabs) neutralizing anti\u2010FVIII antib towards heavy and light chains fully protect FVIII function","volume":"3","author":"Gilles JG","year":"2005","journal-title":"J Thromb Haemost"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2516.2006.01374.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2516.2006.01374.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T12:19:00Z","timestamp":1695730740000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2516.2006.01374.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,11,10]]},"references-count":36,"journal-issue":{"issue":"s6","published-print":{"date-parts":[[2006,12]]}},"alternative-id":["10.1111\/j.1365-2516.2006.01374.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2516.2006.01374.x","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,11,10]]}}}