{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:04:38Z","timestamp":1789617878538,"version":"build-2803163510"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T00:00:00Z","timestamp":1706572800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Emicizumab is used as a subcutaneous prophylaxis for prevention of bleeding episodes in patients with haemophilia A (HA) with and without inhibitors. While low bleeding rates were observed in clinical trials, patients still experience breakthrough bleeds (BTBs) with emicizumab in the real\u2010world. Current guidelines recommend use of recombinant activated factor VII (rFVIIa) for treatment of BTBs in patients with inhibitors. Due to thrombotic events observed in the HAVEN 1 study, activated prothrombin complex concentrate (aPCC) should be used with caution.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The objective of this review is to identify and discuss real\u2010world data on the frequency of BTBs and the safety of concomitant rFVIIa use in patients with inhibitors on emicizumab prophylaxis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A search of the following databases was conducted on 15 July 2022: BIOSIS Previews<jats:sup>\u00ae<\/jats:sup>, Current Contents Search<jats:sup>\u00ae<\/jats:sup>, Embase<jats:sup>\u00ae<\/jats:sup>, MEDLINE<jats:sup>\u00ae<\/jats:sup>. Search terms included \u2018real world\u2019, \u2018haemophilia A\u2019, and \u2018emicizumab\u2019.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and conclusions<\/jats:title><jats:p>Eleven relevant publications were identified (seven original research articles and four congress abstracts). The frequency of BTBs specifically for HA patients with inhibitors was described in three publications with 5%\u201356% patients on emicizumab reporting \u22651 bleeding episode. Treatment of these BTBs appeared to be managed according to relevant guidelines. Importantly, no thrombotic complications occurred during concomitant rFVIIa use. Due to the nature of real\u2010world studies, direct comparison of the results between studies is limited. However, real\u2010world data show that BTBs in inhibitor patients during emicizumab prophylaxis can be safely treated with rFVIIa.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.14933","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T05:39:12Z","timestamp":1706679552000},"page":"267-275","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Safety of recombinant activated factor VII for treatment of breakthrough bleeds in patients with congenital haemophilia A and inhibitors receiving emicizumab prophylaxis: Review of the real\u2010world evidence"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1279-2557","authenticated-orcid":false,"given":"Gili","family":"Kenet","sequence":"first","affiliation":[{"name":"The Israeli National Hemophilia Center and Thrombosis Unit Sheba Medical Center and the Amalia Biron Research Institute of Thrombosis and Hemostasis Tel Aviv University  Tel Hashomer Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6959-6346","authenticated-orcid":false,"given":"Teruhisa","family":"Fujii","sequence":"additional","affiliation":[{"name":"Division of Blood Transfusion Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14046"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100040\u20101714279"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1803550"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1703068"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352\u20103026(19)30054\u20107"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/rth2.12670"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019001869"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.2450\/2019.0186\u201019"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1055\/a\u20101127\u20106476"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13817"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.2450\/2019.0026\u201019"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.27886"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14318"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.16964"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14432"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14005"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14261"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/rth2.12571"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.15187"},{"key":"e_1_2_10_21_1","article-title":"Efficacy of emicizumab prophylaxis in patients with severe hemophilia A in Germany: real\u2010life\u2010data documented by eDiarysmart medication","author":"Mondorf W","year":"2022","journal-title":"International Society on Thrombosis and Haemostasis"},{"key":"e_1_2_10_22_1","first-page":"519","volume-title":"International Society on Thrombosis and Haemostasis","author":"Catarino C","year":"2020"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009217"},{"key":"e_1_2_10_24_1","volume-title":"International Society on Thrombosis and Haemostasis","author":"Kenet G","year":"2020"},{"key":"e_1_2_10_25_1","article-title":"Real\u2010world experience using emicizumab prophylaxis for hemophilia a: single\u2010center experience","author":"Vagrecha A","year":"2020","journal-title":"American Society of Hematology"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100037\u20101608943"},{"key":"e_1_2_10_27_1","unstructured":"Campani\u00e7oS RodriguesF PereiraA RochaE CevadinhaG CatarinoC Is zero bleeds in PWH an achievable goal? 3 years of emicizumab in persons with hemophilia A and inhibitors in a Portuguese hemophilia treatment centers.International Congress on Thrombosis and Haemostasis;2021."},{"key":"e_1_2_10_28_1","first-page":"30","article-title":"Surgical management of paediatric patients on emicizumab prophylaxis","author":"Hassan E","year":"2021","journal-title":"Br J Haematol"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14212"},{"key":"e_1_2_10_30_1","unstructured":"RenerK An\u017eej DomaS Faganel KotnikB KitanovskiL FinkM Prelo\u017enik ZupanI.Emicizumab prophylaxis in haemophilia A with and without inhibitors: real\u2010world data from Slovenia.European Association for Haemophilia and Allied Disorders;2021."},{"key":"e_1_2_10_31_1","article-title":"Invasive procedures in patients with haemophilia on emicizumab prophylaxis: real\u2010world clinical experience in Slovenia","author":"Rener K","year":"2022","journal-title":"European Association for Haemophilia and Allied Disorders"},{"key":"e_1_2_10_32_1","volume-title":"International Society on Thrombosis and Haemostasis","author":"Windyga J","year":"2021"},{"key":"e_1_2_10_33_1","article-title":"Real\u2010world safety of emicizumab: the first interim analysis of the European Haemophilia Safety Surveillance (EUHASS) database","author":"Shang A","year":"2020","journal-title":"American Society of Hematology"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.14933","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T02:06:48Z","timestamp":1714442808000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.14933"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,30]]},"references-count":32,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1111\/hae.14933"],"URL":"https:\/\/doi.org\/10.1111\/hae.14933","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,30]]},"assertion":[{"value":"2023-03-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}