{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T22:23:25Z","timestamp":1789511005050,"version":"build-2803163510"},"reference-count":97,"publisher":"American Society of Hematology","issue":"10","license":[{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/legalcode"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,9,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Disorders of coagulation, resulting in serious risks for bleeding, may be caused by autoantibody formation or by mutations in genes encoding coagulation factors. In the latter case, antidrug antibodies (ADAs) may form against the clotting factor protein drugs used in replacement therapy, as is well documented in the treatment of the X-linked disease hemophilia. Such neutralizing antibodies against factors VIII or IX substantially complicate treatment. Autoantibody formation against factor VIII leads to acquired hemophilia. Although rare, antibody formation may occur in the treatment of other clotting factor deficiencies (eg, against von Willebrand factor [VWF]). The main strategies that have emerged to address these immune responses include (1) clinical immune tolerance induction (ITI) protocols; (2) immune suppression therapies (ISTs); and (3) the development of drugs that can improve hemostasis while bypassing the antibodies against coagulation factors altogether (some of these nonfactor therapies\/NFTs are antibody-based, but they are distinct from traditional immunotherapy as they do not target the immune system). Choice of immune or alternative therapy and criteria for selection of a specific regimen for inherited and autoimmune bleeding disorders are explained. ITI serves as an important proof of principle that antigen-specific immune tolerance can be achieved in humans through repeated antigen administration, even in the absence of immune suppression. Finally, novel immunotherapy approaches that are still in the preclinical phase, such as cellular (for instance, regulatory T cell [Treg]) immunotherapies, gene therapy, and oral antigen administration, are discussed.<\/jats:p>","DOI":"10.1182\/blood.2022016530","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T19:01:44Z","timestamp":1657134104000},"page":"1075-1085","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":18,"title":["Immune complications and their management in inherited and acquired bleeding disorders"],"prefix":"10.1182","volume":"140","author":[{"given":"Valder R.","family":"Arruda","sequence":"first","affiliation":[{"name":"1Raymond G. Perelman Center for Cellular and Molecular Therapeutics at The Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"},{"name":"2Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Lillicrap","sequence":"additional","affiliation":[{"name":"3Department of Pathology and Molecular Medicine, Queen\u2019s University, Kingston, ON, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7213-998X","authenticated-orcid":false,"given":"Roland W.","family":"Herzog","sequence":"additional","affiliation":[{"name":"4Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, 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