{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T04:23:00Z","timestamp":1790310180680,"version":"4.1.0"},"reference-count":82,"publisher":"Georg Thieme Verlag KG","issue":"08","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Thromb Hemost"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The availability first in the 1970s of plasma-derived and then in the 1990s of recombinant clotting factor concentrates represented a milestone in hemophilia care, enabling not only treatment of episodic bleeding events but also implementation of prophylactic regimens. The treatment of hemophilia has recently reached new landmarks. The traditional clotting factor replacement therapy for hemophilia has been substituted over the last 10 years by novel treatments such as bioengineered factor VIII and IX molecules with extended half-life and non-factor treatments including the bispecific antibody emicizumab. This narrative review is dedicated to these newer therapies, which are contributing significantly to improving the long-term management of prophylaxis in hemophilia patients. Another section is focused on the current state of gene therapy, which is a promising definitive cure for severe hemophilia A and B.<\/jats:p>","DOI":"10.1055\/s-0042-1756188","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T18:47:41Z","timestamp":1663267661000},"page":"904-910","source":"Crossref","is-referenced-by-count":47,"title":["The More Recent History of Hemophilia Treatment"],"prefix":"10.1055","volume":"48","author":[{"given":"Massimo","family":"Franchini","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine and Hematology, Carlo Poma Hospital, Mantova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Mannuccio","family":"Mannucci","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico and University of Milan, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2022,9,15]]},"reference":[{"issue":"23","key":"ref1","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1056\/NEJM200106073442307","article-title":"The hemophilias\u2014from royal genes to gene therapy","volume":"344","author":"P M Mannucci","year":"2001","journal-title":"N Engl J Med"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1016\/S0140-6736(03)13405-8","article-title":"Haemophilias A and B","volume":"361","author":"P H Bolton-Maggs","year":"2003","journal-title":"Lancet"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0140-6736(15)01123-X","article-title":"The past and future of haemophilia: diagnosis, treatments, and its complications","volume":"388","author":"F Peyvandi","year":"2016","journal-title":"Lancet"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1750-1172-7-24","article-title":"Past, present and future of hemophilia: a narrative review","volume":"7","author":"M Franchini","year":"2012","journal-title":"Orphanet J Rare Dis"},{"issue":"04","key":"ref5","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.blre.2013.06.002","article-title":"Hemophilia A in the third millennium","volume":"27","author":"M Franchini","year":"2013","journal-title":"Blood Rev"},{"issue":"05","key":"ref6","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1055\/s-0034-1381232","article-title":"The history of hemophilia","volume":"40","author":"M Franchini","year":"2014","journal-title":"Semin Thromb Hemost"},{"issue":"S 01","key":"ref7","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1016\/j.thromres.2013.10.020","article-title":"The history of haemophilia\u2014a short review","volume":"134","author":"W Schramm","year":"2014","journal-title":"Thromb Res"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1126\/science.1180660","article-title":"Genotype analysis identifies the cause of the \u201croyal disease\u201d","volume":"326","author":"E I Rogaev","year":"2009","journal-title":"Science"},{"issue":"S 03","key":"ref9","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/j.1365-2516.2008.01708.x","article-title":"Back to the future: a recent history of haemophilia treatment","volume":"14","author":"P M Mannucci","year":"2008","journal-title":"Haemophilia"},{"issue":"07","key":"ref10","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1046\/j.1538-7836.2003.00262.x","article-title":"Hemophilia: treatment options in the twenty-first century","volume":"1","author":"P M Mannucci","year":"2003","journal-title":"J Thromb Haemost"},{"issue":"27","key":"ref11","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1056\/NEJM196512302732701","article-title":"Production of high-potency concentrates of antihemophilic globulin in a closed-bag system","volume":"273","author":"J G Pool","year":"1965","journal-title":"N Engl J Med"},{"key":"ref12","first-page":"16","article-title":"Experience with prophylaxis in Sweden","volume":"30","author":"I M Nilsson","year":"1993","journal-title":"Semin Hematol"},{"issue":"02","key":"ref13","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1097\/MBC.0000000000000783","article-title":"A history of prophylaxis in haemophilia","volume":"30","author":"M M Moreno","year":"2019","journal-title":"Blood Coagul Fibrinolysis"},{"issue":"S 01","key":"ref14","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1046\/j.1365-2516.2000.00059.x","article-title":"Desmopressin (DDAVP) in the treatment of bleeding disorders: the first twenty years","volume":"6","author":"P M Mannucci","year":"2000","journal-title":"Haemophilia"},{"issue":"11","key":"ref15","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1111\/j.1538-7836.2006.02213.x","article-title":"The tragic history of AIDS in the hemophilia population, 1982-1984","volume":"4","author":"B L Evatt","year":"2006","journal-title":"J Thromb Haemost"},{"issue":"02","key":"ref16","first-page":"178","article-title":"The modern treatment of haemophilia: a narrative review","volume":"11","author":"M Franchini","year":"2013","journal-title":"Blood Transfus"},{"issue":"06","key":"ref17","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1056\/NEJMoa067659","article-title":"Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia","volume":"357","author":"M J Manco-Johnson","year":"2007","journal-title":"N Engl J Med"},{"issue":"04","key":"ref18","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1111\/j.1538-7836.2011.04214.x","article-title":"A randomized clinical trial of prophylaxis in children with hemophilia A (the ESPRIT Study)","volume":"9","author":"A Gringeri","year":"2011","journal-title":"J Thromb Haemost"},{"issue":"10","key":"ref19","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1080\/14740338.2016.1208747","article-title":"The safety of pharmacologic options for the treatment of persons with hemophilia","volume":"15","author":"M Franchini","year":"2016","journal-title":"Expert Opin Drug Saf"},{"issue":"03","key":"ref20","doi-asserted-by":"crossref","first-page":"545","DOI":"10.3324\/haematol.2019.232132","article-title":"Hemophilia therapy: the future has begun","volume":"105","author":"P M Mannucci","year":"2020","journal-title":"Haematologica"},{"issue":"S 02","key":"ref21","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1016\/S0049-3848(13)70150-6","article-title":"Innovative coagulation factors: albumin fusion technology and recombinant single-chain factor VIII","volume":"131","author":"S Schulte","year":"2013","journal-title":"Thromb Res"},{"issue":"01","key":"ref22","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1365-2516.2012.02931.x","article-title":"PEGylated therapeutic proteins for haemophilia treatment: a review for haemophilia caregivers","volume":"19","author":"I A Ivens","year":"2013","journal-title":"Haemophilia"},{"issue":"04","key":"ref23","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1517\/14728214.2015.1113254","article-title":"What is the future of PEGylated therapies?","volume":"20","author":"M Swierczewska","year":"2015","journal-title":"Expert Opin Emerg Drugs"},{"issue":"06","key":"ref24","first-page":"479","article-title":"Factor VIII replacement is still the standard of care in haemophilia A","volume":"17","author":"L Aledort","year":"2019","journal-title":"Blood Transfus"},{"issue":"06","key":"ref25","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1111\/ejh.13610","article-title":"Recombinant factor VIII Fc for the treatment of haemophilia A","volume":"106","author":"C Hermans","year":"2021","journal-title":"Eur J Haematol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"103678","DOI":"10.1016\/j.critrevonc.2022.103678","article-title":"Clinical studies of extended-half-life recombinant FVIII products for prophylaxis in adults and children: a critical review from the physician's perspective","volume":"174","author":"C Hermans","year":"2022","journal-title":"Crit Rev Oncol Hematol"},{"issue":"03","key":"ref27","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1182\/blood-2011-07-367003","article-title":"Recombinant factor IX-Fc fusion protein (rFIXFc) demonstrates safety and prolonged activity in a phase 1\/2a study in hemophilia B patients","volume":"119","author":"A D Shapiro","year":"2012","journal-title":"Blood"},{"issue":"24","key":"ref28","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1056\/NEJMoa1305074","article-title":"Phase 3 study of recombinant factor IX Fc fusion protein in hemophilia B","volume":"369","author":"J S Powell","year":"2013","journal-title":"N Engl J Med"},{"issue":"13","key":"ref29","doi-asserted-by":"crossref","first-page":"2732","DOI":"10.1182\/bloodadvances.2020004085","article-title":"Final results of the PUPs B-LONG study: evaluating safety and efficacy of rFIXFc in previously untreated patients with hemophilia B","volume":"5","author":"B Nolan","year":"2021","journal-title":"Blood Adv"},{"issue":"26","key":"ref30","doi-asserted-by":"crossref","first-page":"3880","DOI":"10.1182\/blood-2014-05-573055","article-title":"Recombinant long-acting glycoPEGylated factor IX in hemophilia B: a multinational randomized phase 3 trial","volume":"124","author":"P W Collins","year":"2014","journal-title":"Blood"},{"issue":"07","key":"ref31","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1002\/rth2.12412","article-title":"Nonacog beta pegol (N9-GP) in hemophilia B: first report on safety and efficacy in previously untreated and minimally treated patients","volume":"4","author":"A K Chan","year":"2020","journal-title":"Res Pract Thromb Haemost"},{"issue":"14","key":"ref32","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1182\/blood-2015-09-669234","article-title":"Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial","volume":"127","author":"E Santagostino","year":"2016","journal-title":"Blood"},{"issue":"03","key":"ref33","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1182\/blood-2013-10-529974","article-title":"Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A","volume":"123","author":"J Mahlangu","year":"2014","journal-title":"Blood"},{"issue":"09","key":"ref34","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1182\/blood-2015-03-630897","article-title":"Pegylated, full-length, recombinant factor VIII for prophylactic and on-demand treatment of severe hemophilia A","volume":"126","author":"B A Konkle","year":"2015","journal-title":"Blood"},{"issue":"02","key":"ref35","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1160\/TH16-06-0444","article-title":"Clinical evaluation of glycoPEGylated recombinant FVIII: efficacy and safety in severe haemophilia A","volume":"117","author":"P Giangrande","year":"2017","journal-title":"Thromb Haemost"},{"issue":"02","key":"ref36","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1111\/hae.13119","article-title":"Extended half-life pegylated, full-length recombinant factor VIII for prophylaxis in children with severe haemophilia A","volume":"23","author":"E S Mullins","year":"2017","journal-title":"Haemophilia"},{"issue":"03","key":"ref37","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1111\/jth.13597","article-title":"Safety and efficacy of BAY 94-9027, a prolonged-half-life factor VIII","volume":"15","author":"M T Reding","year":"2017","journal-title":"J Thromb Haemost"},{"issue":"03","key":"ref38","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1111\/hae.13953","article-title":"Recombinant factor VIII Fc fusion protein for the treatment of severe haemophilia A: final results from the ASPIRE extension study","volume":"26","author":"B Nolan","year":"2020","journal-title":"Haemophilia"},{"issue":"03","key":"ref39","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1002\/rth2.12220","article-title":"Fixed doses of N8-GP prophylaxis maintain moderate-to-mild factor VIII levels in the majority of patients with severe hemophilia A","volume":"3","author":"P Chowdary","year":"2019","journal-title":"Res Pract Thromb Haemost"},{"issue":"09","key":"ref40","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1160\/TH17-03-0166","article-title":"Safety and efficacy of a glycoPEGylated rFVIII (turoctocog alpha pegol, N8-GP) in paediatric patients with severe haemophilia A","volume":"117","author":"S Meunier","year":"2017","journal-title":"Thromb Haemost"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.thromres.2019.08.023","article-title":"Safety and efficacy of BAY 94-9027, an extended-half-life factor VIII, during surgery in patients with severe hemophilia A: results of the PROTECT VIII clinical trial","volume":"183","author":"E Santagostino","year":"2019","journal-title":"Thromb Res"},{"issue":"26","key":"ref42","doi-asserted-by":"crossref","first-page":"3699","DOI":"10.1182\/blood.2021013563","article-title":"First study of extended half-life rFVIIIFc in previously untreated patients with hemophilia A: PUPs A-LONG final results","volume":"139","author":"C K\u00f6nigs","year":"2022","journal-title":"Blood"},{"issue":"16","key":"ref43","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1182\/blood-2016-04-713289","article-title":"Life in the shadow of a dominant partner: the FVIII-VWF association and its clinical implications for hemophilia A","volume":"128","author":"S W Pipe","year":"2016","journal-title":"Blood"},{"issue":"11","key":"ref44","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1056\/NEJMoa2002699","article-title":"BIVV001 fusion protein as factor VIII replacement therapy for hemophilia A","volume":"383","author":"B A Konkle","year":"2020","journal-title":"N Engl J Med"},{"issue":"04","key":"ref45","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3390\/jcm6040039","article-title":"Outcome of clinical trials with new extended half-life FVIII\/IX concentrates","volume":"6","author":"M E Mancuso","year":"2017","journal-title":"J Clin Med"},{"issue":"05","key":"ref46","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1111\/hae.13807","article-title":"Perioperative haemostasis with full-length, PEGylated, recombinant factor VIII with extended half-life (rurioctocog alfa pegol) in patients with haemophilia A: final results of a multicentre, single-arm phase III trial","volume":"25","author":"R Gruppo","year":"2019","journal-title":"Haemophilia"},{"issue":"12","key":"ref47","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1182\/blood-2012-05-429688","article-title":"Safety and pharmacokinetics of a novel recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in hemophilia B patients","volume":"120","author":"E Santagostino","year":"2012","journal-title":"Blood"},{"issue":"03","key":"ref48","doi-asserted-by":"crossref","first-page":"e12695","DOI":"10.1002\/rth2.12695","article-title":"Impact of novel hemophilia therapies around the world","volume":"6","author":"M C Ozelo","year":"2022","journal-title":"Res Pract Thromb Haemost"},{"issue":"04","key":"ref49","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1111\/j.1365-2125.2010.03899.x","article-title":"Inhibitors of propagation of coagulation (factors VIII, IX and XI): a review of current therapeutic practice","volume":"72","author":"M Franchini","year":"2011","journal-title":"Br J Clin Pharmacol"},{"issue":"S 05","key":"ref50","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/j.1365-2516.2010.02294.x","article-title":"Clinical issues in inhibitors","volume":"16","author":"J Astermark","year":"2010","journal-title":"Haemophilia"},{"issue":"01","key":"ref51","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3324\/haematol.2019.239160","article-title":"Inhibitor incidence in an unselected cohort of previously untreated patients with severe haemophilia B: a PedNet study","volume":"106","author":"C Male","year":"2021","journal-title":"Haematologica"},{"issue":"01","key":"ref52","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1182\/asheducation-2016.1.657","article-title":"Hemophilia and inhibitors: current treatment options and potential new therapeutic approaches","volume":"2016","author":"S L Meeks","year":"2016","journal-title":"Hematology (Am Soc Hematol Educ Program)"},{"issue":"21","key":"ref53","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1056\/NEJMoa1516437","article-title":"A randomized trial of factor VIII and neutralizing antibodies in hemophilia A","volume":"374","author":"F Peyvandi","year":"2016","journal-title":"N Engl J Med"},{"issue":"02","key":"ref54","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1182\/blood-2006-04-017988","article-title":"A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor: the FEIBA NovoSeven Comparative (FENOC) Study","volume":"109","author":"J Astermark","year":"2007","journal-title":"Blood"},{"issue":"01","key":"ref55","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1007\/s12325-008-0135-6","article-title":"Systematic review of efficacy of rFVIIa and aPCC treatment for hemophilia patients with inhibitors","volume":"26","author":"C Knight","year":"2009","journal-title":"Adv Ther"},{"issue":"02","key":"ref56","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1111\/j.1365-2516.2008.01956.x","article-title":"Efficacy of recombinant activated factor VII vs. activated prothrombin complex concentrate for patients suffering from haemophilia complicated with inhibitors: a Bayesian meta-regression","volume":"15","author":"M J Treur","year":"2009","journal-title":"Haemophilia"},{"issue":"07","key":"ref57","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1055\/s-0033-1354425","article-title":"FEIBA versus NovoSeven in hemophilia patients with inhibitors","volume":"39","author":"M Franchini","year":"2013","journal-title":"Semin Thromb Hemost"},{"issue":"05","key":"ref58","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1055\/s-0036-1571310","article-title":"Innovative pharmacological therapies for the hemophilias not based on deficient factor replacement","volume":"42","author":"P M Mannucci","year":"2016","journal-title":"Semin Thromb Hemost"},{"issue":"05","key":"ref59","first-page":"457","article-title":"Non-factor replacement therapy for haemophilia: a current update","volume":"16","author":"M Franchini","year":"2018","journal-title":"Blood Transfus"},{"issue":"10","key":"ref60","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1038\/nm.2942","article-title":"A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model","volume":"18","author":"T Kitazawa","year":"2012","journal-title":"Nat Med"},{"issue":"13","key":"ref61","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1182\/blood-2015-06-650226","article-title":"A first-in-human phase 1 study of ACE910, a novel factor VIII-mimetic bispecific antibody, in healthy subjects","volume":"127","author":"N Uchida","year":"2016","journal-title":"Blood"},{"issue":"21","key":"ref62","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1056\/NEJMoa1511769","article-title":"Factor VIII-mimetic function of humanized bispecific antibody in hemophilia A","volume":"374","author":"M Shima","year":"2016","journal-title":"N Engl J Med"},{"issue":"09","key":"ref63","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1056\/NEJMoa1703068","article-title":"Emicizumab prophylaxis in hemophilia A with inhibitors","volume":"377","author":"J Oldenburg","year":"2017","journal-title":"N Engl J Med"},{"issue":"16","key":"ref64","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1182\/blood.2020009217","article-title":"Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1-4 studies","volume":"137","author":"M U Callaghan","year":"2021","journal-title":"Blood"},{"issue":"09","key":"ref65","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1056\/NEJMoa1803550","article-title":"Emicizumab prophylaxis in patients who have hemophilia A without inhibitors","volume":"379","author":"J Mahlangu","year":"2018","journal-title":"N Engl J Med"},{"issue":"06","key":"ref66","doi-asserted-by":"crossref","first-page":"e295","DOI":"10.1016\/S2352-3026(19)30054-7","article-title":"Efficacy, safety, and pharmacokinetics of emicizumab prophylaxis given every 4 weeks in people with haemophilia A (HAVEN 4): a multicentre, open-label, non-randomised phase 3 study","volume":"6","author":"S W Pipe","year":"2019","journal-title":"Lancet Haematol"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.blre.2019.03.002","article-title":"Factor VIII: Long-established role in haemophilia A and emerging evidence beyond haemostasis","volume":"35","author":"B Samuelson Bannow","year":"2019","journal-title":"Blood Rev"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1111\/hae.14172","article-title":"Management of patients with severe haemophilia A without inhibitors on prophylaxis with emicizumab: AICE recommendations with focus on emergency in collaboration with SIBioC, SIMEU, SIMEUP, SIPMeL and SISET","volume":"26","author":"A Coppola","year":"2020","journal-title":"Haemophilia"},{"issue":"02","key":"ref69","first-page":"143","article-title":"Emergency management in patients with haemophilia A and inhibitors on prophylaxis with emicizumab: AICE practical guidance in collaboration with SIBioC, SIMEU, SIMEUP, SIPMeL and SISET","volume":"18","author":"G Castaman","year":"2020","journal-title":"Blood Transfus"},{"issue":"20","key":"ref70","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.1182\/bloodadvances.2018015859","article-title":"Emicizumab should be prescribed independent of immune tolerance induction","volume":"2","author":"S Le Quellec","year":"2018","journal-title":"Blood Adv"},{"issue":"03","key":"ref71","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1159\/000495454","article-title":"Inhibitors: a need for eradication?","volume":"141","author":"E Santagostino","year":"2019","journal-title":"Acta Haematol"},{"issue":"03","key":"ref72","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1620\/tjem.256.197","article-title":"Current therapies in hemophilia: from plasma-derived factor modalities to CRISPR\/Cas alternatives","volume":"256","author":"I Jair Lara-Navarro","year":"2022","journal-title":"Tohoku J Exp Med"},{"issue":"07","key":"ref73","doi-asserted-by":"crossref","first-page":"3906","DOI":"10.1073\/pnas.96.7.3906","article-title":"Sustained correction of bleeding disorder in hemophilia B mice by gene therapy","volume":"96","author":"L Wang","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"05","key":"ref74","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1182\/blood.V95.5.1594.005k34_1594_1599","article-title":"Sustained expression of human factor VIII in mice using a parvovirus-based vector","volume":"95","author":"H Chao","year":"2000","journal-title":"Blood"},{"issue":"03","key":"ref75","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1182\/blood-2010-05-282707","article-title":"Codon optimization of human factor VIII cDNAs leads to high-level expression","volume":"117","author":"N J Ward","year":"2011","journal-title":"Blood"},{"issue":"05","key":"ref76","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1182\/bloodadvances.2019000405","article-title":"Evolutionary insights into coagulation factor IX Padua and other high-specific-activity variants","volume":"5","author":"B J Samelson-Jones","year":"2021","journal-title":"Blood Adv"},{"issue":"S 01","key":"ref77","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1182\/blood-2018-99-118334","article-title":"Adeno-associated mediated gene transfer for hemophilia B: 8 year follow up and impact of removing \u201cempty viral particles\u201d on safety and efficacy of gene transfer","volume":"132","author":"A C Nathwani","year":"2018","journal-title":"Blood"},{"issue":"03","key":"ref78","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/nm1358","article-title":"Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response","volume":"12","author":"C S Manno","year":"2006","journal-title":"Nat Med"},{"issue":"01","key":"ref79","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1056\/NEJMoa1908490","article-title":"Multiyear follow-up of AAV5-hFVIII-SQ gene therapy for hemophilia A","volume":"382","author":"K J Pasi","year":"2020","journal-title":"N Engl J Med"},{"issue":"21","key":"ref80","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1056\/NEJMoa2104205","article-title":"Multiyear factor VIII expression after AAV gene transfer for hemophilia A","volume":"385","author":"L A George","year":"2021","journal-title":"N Engl J Med"},{"issue":"11","key":"ref81","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1056\/NEJMoa2113708","article-title":"Valoctocogene roxaparvovec gene therapy for hemophilia A","volume":"386","author":"M C Ozelo","year":"2022","journal-title":"N Engl J Med"},{"issue":"03","key":"ref82","doi-asserted-by":"crossref","first-page":"e86","DOI":"10.1111\/hae.14546","article-title":"Gene therapy of hemophilia: Hub centres should be haemophilia centres: a joint publication of EAHAD and EHC","volume":"28","author":"W Miesbach","year":"2022","journal-title":"Haemophilia"}],"container-title":["Seminars in Thrombosis and Hemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0042-1756188.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T19:37:05Z","timestamp":1668713825000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0042-1756188"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,15]]},"references-count":82,"journal-issue":{"issue":"08","published-online":{"date-parts":[[2022,11,17]]},"published-print":{"date-parts":[[2022,11]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0042-1756188","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0094-6176","1098-9064"],"issn-type":[{"value":"0094-6176","type":"print"},{"value":"1098-9064","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,15]]}}}