{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,10]],"date-time":"2024-08-10T05:57:07Z","timestamp":1723269427787},"reference-count":0,"publisher":"Georg Thieme Verlag KG","issue":"06","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Thromb Hemost"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nonsevere hemophilia A (NSHA) is an inherited X-linked bleeding disorder, caused by mutations of the F8 gene, leading to decreases of clotting factor VIII (FVIII) levels to 1 to 40 IU\/dL. Desmopressin is the first therapeutic option for NSHA, but 40 to 50% of patients fail to attain adequate postinfusion FVIII levels. Thus, in these cases, FVIII concentrates remain the mainstay of treatment. The development of neutralizing FVIII antibodies (inhibitors) is a major challenge with replacement therapy. In contrast to severe disease, NSHA patients have a lifelong risk of inhibitor development. Recent data indicate that inhibitors are associated with a deterioration of clinical outcome, illustrated by an increase in bleeding and mortality rate. F8 genotype is an important risk factor for inhibitor occurrence together with surgical interventions and a high dose of FVIII concentrate. Adequate prevention and treatment of inhibitors in NSHA patients is limited by a lack of understanding of the underlying immunological mechanisms. Elucidation of the immunology driving inhibitor development is required to identify high-risk patients, to understand the association between clinical risk factors and inhibitor occurrence, and to provide the opportunity to develop new preventive and therapeutic strategies.<\/jats:p>","DOI":"10.1055\/s-0037-1621717","type":"journal-article","created":{"date-parts":[[2018,2,13]],"date-time":"2018-02-13T18:34:46Z","timestamp":1518546886000},"page":"568-577","source":"Crossref","is-referenced-by-count":8,"title":["Inhibitors in Nonsevere Hemophilia A: What Is Known and Searching for the Unknown"],"prefix":"10.1055","volume":"44","author":[{"given":"Amal","family":"Abdi","sequence":"first","affiliation":[{"name":"Department of Pediatric Hematology, Amsterdam Medical Center, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Linari","sequence":"first","affiliation":[{"name":"Department of Oncology, Center for Bleeding Disorders and Coagulation, Careggi University Hospital, Firenze, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Pieri","sequence":"first","affiliation":[{"name":"Department of Oncology, Center for Bleeding Disorders and Coagulation, Careggi University Hospital, Firenze, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Voorberg","sequence":"first","affiliation":[{"name":"Sanquin, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Fijnvandraat","sequence":"first","affiliation":[{"name":"Department of Pediatric Hematology, Amsterdam Medical Center, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giancarlo","family":"Castaman","sequence":"additional","affiliation":[{"name":"Department of Oncology, Center for Bleeding Disorders and Coagulation, Careggi University Hospital, Firenze, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2018,2,13]]},"container-title":["Seminars in Thrombosis and Hemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0037-1621717.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,8,31]],"date-time":"2018-08-31T18:33:50Z","timestamp":1535740430000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0037-1621717"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,13]]},"references-count":0,"journal-issue":{"issue":"06","published-online":{"date-parts":[[2018,8,31]]},"published-print":{"date-parts":[[2018,9]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0037-1621717","relation":{},"ISSN":["0094-6176","1098-9064"],"issn-type":[{"value":"0094-6176","type":"print"},{"value":"1098-9064","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,13]]}}}