{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T02:37:05Z","timestamp":1777775825173,"version":"3.51.4"},"reference-count":55,"publisher":"Walter de Gruyter GmbH","issue":"3","license":[{"start":{"date-parts":[[2018,8,29]],"date-time":"2018-08-29T00:00:00Z","timestamp":1535500800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:bold>Introduction<\/jats:bold>\n                    . Our research strategy was aimed at evaluating the possible implication of the type of factor VIII product administered as substitution treatment to haemophilia A patients in the occurrence of inhibitors and their consequences on the management.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods<\/jats:bold>\n                    . Scientific articles from July 2015 to July 2017 were searched using the PubMed and PubMed Central databases. The used search terms included \u201chaemophilia A\u201d, \u201cinhibitors\u201d, \u201cplasma-derived factor VIII\u201d and \u201crecombinant factor VIII\u201d.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results<\/jats:bold>\n                    . The risk factors for inhibitors occurrence may be patients-related (genetic and nongenetic) and treatment-related. The possibility of a correlation between the increased purity of factor VIII given as substitution treatment and the occurrence of inhibitors is discussed in the light of literature data. Plasma-derived factor VIII is less immunogenic, but not entirely safe from the point of view of the possibility of transmitting biological agents. It is obvious that there is not enough plasma-derived factor VIII for the planet\u2019s needs. Recombinant factor VIII products have revolutionized the treatment of patients with haemophilia A over the past 3 decades by the disappearance of transfusion-related infections and their complications. They are safer in terms of pathogens and the new long-acting factor VIII products are based on recombinant DNA technology.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion<\/jats:bold>\n                    . Plasma-derived or recombinant factor VIII products must co-exist on the market for the benefit of haemophilic patients. Future solutions could be: less immunogenic factor VIII products, nonfactor replacement strategies, or bispecific antibody that mimics the function of coagulation factor VIII.\n                  <\/jats:p>","DOI":"10.2478\/rjim-2018-0013","type":"journal-article","created":{"date-parts":[[2018,5,23]],"date-time":"2018-05-23T18:16:42Z","timestamp":1527099402000},"page":"143-152","source":"Crossref","is-referenced-by-count":0,"title":["The inhibitors \u2013 a challenge for the management of patients with hereditary haemophilia A"],"prefix":"10.2478","volume":"56","author":[{"given":"Romeo-Gabriel","family":"Mih\u0103il\u0103","sequence":"first","affiliation":[{"name":"Faculty of Medicine , \u201cLucian Blaga\u201d University of Sibiu , and Department of Hematology, Emergency County Clinical Hospital Sibiu , Sibiu , Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2018,8,29]]},"reference":[{"key":"2026042914150229837_j_rjim-2018-0013_ref_001_w2aab3b7b9b1b6b1ab1ab1Aa","doi-asserted-by":"crossref","unstructured":"1. 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Blood. 2010; 116:5842-5848.10.1182\/blood-2010-06-288001303138020876851","DOI":"10.1182\/blood-2010-06-288001"},{"key":"2026042914150229837_j_rjim-2018-0013_ref_004_w2aab3b7b9b1b6b1ab1ab4Aa","doi-asserted-by":"crossref","unstructured":"4. LAI J., HOUGH C., TARRANT J., LILLICRAP D. Biological considerations of plasma-derived and recombinant factor VIII immunogenicity. Blood. 2017; 129:3147-3154.10.1182\/blood-2016-11-75088528432221","DOI":"10.1182\/blood-2016-11-750885"},{"key":"2026042914150229837_j_rjim-2018-0013_ref_005_w2aab3b7b9b1b6b1ab1ab5Aa","doi-asserted-by":"crossref","unstructured":"5. OWAIDAH T., MOMEN A.A., ALZAHRANI H., ALMUSA A., ALKASIM F., TARAWAH A., et al. The prevalence of factor VIII and IX inhibitors among Saudi patients with hemophilia: Results from the Saudi national hemophilia screening program. Medicine (Baltimore). 2017; 96:e5456.10.1097\/MD.0000000000005456526615028079788","DOI":"10.1097\/MD.0000000000005456"},{"key":"2026042914150229837_j_rjim-2018-0013_ref_006_w2aab3b7b9b1b6b1ab1ab6Aa","doi-asserted-by":"crossref","unstructured":"6. BENSON G., AUERSWALD G., ELEZOVI\u0106 I., LAMBERT T., LJUNG R., MORFINI M., et al. Immune tolerance induction in patients with severe hemophilia with inhibitors: expert panel views and recommendations for clinical practice. Eur J Haematol. 2012; 88:371-379.10.1111\/j.1600-0609.2012.01754.x22260405","DOI":"10.1111\/j.1600-0609.2012.01754.x"},{"key":"2026042914150229837_j_rjim-2018-0013_ref_007_w2aab3b7b9b1b6b1ab1ab7Aa","doi-asserted-by":"crossref","unstructured":"7. ROCINO A., FRANCHINI M., COPPOLA A. Treatment and Prevention of Bleeds in Haemophilia Patients with Inhibitors to Factor VIII\/IX. 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Eur J Haematol. 2015; 94 Suppl 77:45-50.10.1111\/ejh.1250125560794","DOI":"10.1111\/ejh.12501"},{"key":"2026042914150229837_j_rjim-2018-0013_ref_017_w2aab3b7b9b1b6b1ab1ac17Aa","doi-asserted-by":"crossref","unstructured":"17. \u00c1LVAREZ T., SOTO I., ASTERMARK J. Non-genetic risk factors and their influence on the management of patients in the clinic. Eur J Haematol. 2015; 94 Suppl 77:2-6.10.1111\/ejh.1249425560787","DOI":"10.1111\/ejh.12494"},{"key":"2026042914150229837_j_rjim-2018-0013_ref_018_w2aab3b7b9b1b6b1ab1ac18Aa","doi-asserted-by":"crossref","unstructured":"18. CARACO M., RE W., EWENSTEIN B. The role of previously untreated patient studies in understanding the development of FVIII inhibitors. Haemophilia. 2016; 22:22-31.10.1111\/hae.1279026315604","DOI":"10.1111\/hae.12790"},{"key":"2026042914150229837_j_rjim-2018-0013_ref_019_w2aab3b7b9b1b6b1ab1ac19Aa","doi-asserted-by":"crossref","unstructured":"19. TER AVEST P.C., FISCHER K., MANCUSO M.E., SANTAGOSTINO E., YUSTE V.J., VAN DEN BERG H.M., et al. Risk stratification for inhibitor development at first treatment for severe hemophilia A: a tool for clinical practice. J Thromb Haemost. 2008; 6:2048-2054.10.1111\/j.1538-7836.2008.03187.x18983511","DOI":"10.1111\/j.1538-7836.2008.03187.x"},{"key":"2026042914150229837_j_rjim-2018-0013_ref_020_w2aab3b7b9b1b6b1ab1ac20Aa","doi-asserted-by":"crossref","unstructured":"20. MARCUCCI M., MANCUSO M.E., SANTAGOSTINO E., KENET G., ELALFY M., HOLZHAUER S., et al. Type and intensity of FVIII exposure on inhibitor development in PUPs with haemophilia A. A patient-level meta-analysis. Thromb Haemost. 2015; 113:958-967.10.1160\/TH14-07-062125631402","DOI":"10.1160\/TH14-07-0621"},{"key":"2026042914150229837_j_rjim-2018-0013_ref_021_w2aab3b7b9b1b6b1ab1ac21Aa","doi-asserted-by":"crossref","unstructured":"21. KURNIK K., BIDLINGMAIER C., ENGL W., CHEHADEH H., REIPERT B., AUERSWALD G. 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