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Protocolo de uso do emicizumabe para tratamento de indiv\u00edduos com hemofilia A e inibidores do fator VIII refrat\u00e1rios ao tratamento de imunotoler\u00e2ncia [Internet]. Bras\u00edlia, 2021. Available from: http:\/\/conitec.gov.br\/images\/Consultas\/Relatorios\/2021\/20210708_Protocolo_de_uso_emicizumabe_CP_64.pdf. Accessed December 2, 2021."},{"key":"10.1002\/rth2.12695_bb0395","unstructured":"World Federation of Hemophilia. WFH Humanitarian Aid Program \u2010 Impact Report 2020 [Internet]. World Federation of Hemophilia, 2021 [cited 2021 Nov 25]. Available from: https:\/\/www1.wfh.org\/publications\/files\/pdf\u20101889.pdf. 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