Immune-Mediated Hemolytic Anemia

Autoimmune diseases are caused by inappropriate immune system responses that target self-antigens. The maintenance of normal peripheral immune tolerance is complex; an important part of this regulation involves regulatory T cells (Tregs). Tregs suppress stimulated effector T-cell and cytotoxic T-cell (in vitro) activation and proliferation by antigenic stimuli.

Traditional broad-spectrum immunosuppressive therapies are associated with significant adverse events. New understanding of immune-mediated diseases has led to research—much of it in rodents and humans—into novel immunotherapies.

This review examined current literature about these therapies and their applicability for immune-mediated hemolytic anemia (IMHA) in dogs.

Monoclonal antibodies are administered in an attempt to deplete the B-cell compartment by binding to autoantibody-producing B-cells, which causes complement-mediated destruction of those cells. It has been hypothesized that subcutaneous or sublingual administration of autoantigens may establish tolerance and control in autoimmune disease cases, much as allergen immunotherapy is used to manage atopic dermatitis in dogs. It may be possible to re-establish tolerance of self-antigens through adoptive Treg transfer.

The authors concluded that continued development of novel immunotherapies will lead to their eventual availability for veterinary patients.

Diagnosis and management of IMHA require an advanced knowledge of the coagulation cascade as well as the cardiovascular, respiratory, and immune systems. A mastery of physiologic concepts such as oxygen delivery and the body’s compensatory response to acute anemia is also required. Patients typically arrive in critical condition; treatment involves blood component therapy, artificial blood, and state-of-the-art immunosuppressive and anticoagulant drugs.

New treatments more specifically address IMHA pathophysiology (eg, use of autologous Tregs) and have fewer side effects than do traditional therapies. Some are being evaluated in clinical trials or might be in the near future (eg, IL-2 therapy) and may soon become available for client-owned patients. Others (eg, rituximab) may never be applicable, and some may only be used in veterinary medicine if significant obstacles are overcome first.

This review suggested that new therapeutic approaches with potential to modify the course of IMHA are on the horizon and may even make curing IMHA a reasonable goal, although they need considerable testing before they can be used in client-owned patients.—Nuno Felix, DVM, MD, MS

This capsule is part of the WSAVA Global Edition of Clinician’s Brief and the One Health Initiative.