Autoantibody production or abnormalities in the genes that code for coagulation factors may result in coagulation disorders that pose substantial hazards for bleeding. As has been well-documented in treating the X-linked disorder hemophilia, in the latter scenario, antidrug antibodies (ADAs) may develop against the clotting factor protein medicines used in replacement therapy.

Treatment was further complicated by such neutralizing antibodies against factors VIII or IX. Acquired hemophilia is caused by the development of autoantibodies against factor VIII. In the rare event that another clotting factor deficiency is treated, antibody development is possible (e.g., against von Willebrand factor [VWF]). Clinical immune tolerance induction (ITI) regimens, immune suppression therapies (ISTs), and other approaches were the major approaches that have evolved to deal with these immune reactions; and the creation of medications that can enhance hemostasis without completely avoiding antibodies against coagulation factors (some of these nonfactor therapies/NFTs are antibody-based, but they differ from conventional immunotherapy in that they do not target the immune system).

There were guidelines for selecting a particular treatment plan for hereditary and autoimmune bleeding diseases and options for immunological or alternative therapies. ITI is a crucial proof of concept that, even in the absence of immune suppression, antigen-specific immunological tolerance may be developed in people by repetitive antigen administration.

Finally, innovative immunotherapy strategies that were in the preclinical stage were reviewed. The strategies included gene therapy, oral antigen delivery, and cellular immunotherapies (such as regulatory T cell [Treg]) immunotherapies.