Just Ask the Expert: Is human IgG a viable treatment for IMHA?
Dr. Byers welcomes critical care questions from veterinarians and veterinary technicians.
Please review the use of human IgG in the treatment of immune-mediated hemolytic anemia (IMHA) in veterinary patients.
Fred L. Metzger Jr., DVM, DABVP
IVIg is a preparation of fractionated immunoglobulins, mostly intact IgG, harvested from pooled human plasma; it also contains trace amounts of IgA; soluble CD4, CD8, and human leukocyte antigen molecules; as well as certain cytokines. After infusion, the half-life of IVIg in dogs is reportedly seven to nine days, but no definitive pharmacokinetic or pharmacodynamic research is available to my knowledge.
The mechanisms of action of IVIG are complex and not entirely understood. They include1,2
1. Inhibiting pathologic autoantibodies via anti-idiotypic antibodies
2. Transiently blocking the function of Fc gamma receptors on phagocytes
3. Modulating complement activation to divert complement away from target tissues to reduce damage
4. Interfering with superantigen activation of cytotoxic T cells.
IVIg has been used to treat several disorders in dogs and cats, but the most experience involves the treatment of idiopathic IMHA in dogs. Specific findings from studies include
IVIg has been used in dogs with nonregenerative anemia and myelofibrosis, thought to be immune-mediated in nature.6 IVIg has also been used in dogs with immune-mediated thrombocytopenia (ITP) and sudden acquired retinal degeneration.7-9 Additional case reports document the use of IVIg in the successful treatment of erythema multiforme in a cat,10 a drug-induced dermatologic reaction in a dog,11 pemphigus foliaceus in a dog,12 and epidermolysis bullosa acquisita in a dog.13
Adverse effects of IVIg in people and dogs are relatively uncommon, and documented incidents include
The production costs and high demand for IVIg in human medicine make this drug extremely expensive. As the diseases in which IVIg may be used are traditionally serious, the lack of authoritative indication that IVIg is helpful in treating immunologic disorders makes justification difficult. Recommendations that IVIg be used when dogs with IMHA fail to respond to conventional therapy must be weighed against the considerable additional cost after clients have already spent a substantial amount of money during initial treatment.
Christopher G. Byers, DVM, DACVECC, DACVIM
1. Bayry J, Thirion M, Misra N, et al. Mechanisms of action of intravenous immunoglobulin in autoimmune and inflammatory diseases. Neurol Sci 2003;24(Suppl 4):S217-S221.
2. Simon HU, Späth PJ. IVIG—mechanisms of action. Allergy 2003;58(7):543-552.
3. Scott-Moncrieff JCR, R agan WJ, Snyder PW, et al. Intravenous administration of human immune globulin in dogs with immune-mediated hemolytic anemia. J Am Vet Med Assoc 1997;210(11):1623-1627.
4. Kellerman DL, Bruyette DS. Intravenous human immunoglobulin for the treatment of immune-mediated hemolytic anemia in 13 dogs. J Vet Intern Med 1997;11(6):327-332.
5. Whelan MF, O'Toole TE, Chan DL, et al. Use of human immunoglobulin in addition to glucocorticoids for the initial treatment of dogs with immune-mediated hemolytic anemia. J Vet Emerg Crit Care 2009;19(2):158-164.
6. Scott-Montcrieff JCR, Reagan WJ, Glickman LT, et al. Treatment of nonregenerative anemia with human gamma-globulin in dogs. J Am Vet Med Assoc 1995;206(12):1895-1900.
7. Bianco D, Armstrong PJ, Washabau RJ. Treatment of severe immune-mediated thrombocytopenia with human IV immunoglobulin in 5 dogs. J Vet Intern Med 2007;21(4):694-699.
8. Bianco D, Armstrong PJ, Washabau RJ. A prospective, randomized, double-blinded, placebo-controlled study of human intravenous immunoglobulin for the acute management of presumptive primary immune-mediated thrombocytopenia in dogs. J Vet Intern Med 2009;23(5):1071-1078.
9. Grozdanic SD, Kecova H, Harper MM, et al. Antibody mediated retinopathy: new mechanisms and treatment strategies, in Proceedings. Am Coll Vet Ophthalmol Conf, 2008.
10. Byrne KP, Giger U. Use of human immunoglobulin for treatment of severe erythema multiforme in a cat. J Am Vet Med Assoc 2002;220(2):197-201.
11. Nuttall TJ, Malham T. Successful intravenous human immunoglobulin treatment of drug-induced Stevens-Johnson syndrome in a dog. J Small Anim Pract 2004;45(7):357-361.
12.. Rahilly LJ, Keating JH, O'Toole TE. The use of intravenous human immunoglobulin in treatment of severe pemphigus foliaceus in a dog. J Vet Intern Med 2006;20(6):1483-1486.
13. Hill PB, Boyer P, Lau P, et al. Epidermolysis bullosa acquisita in a Great Dane. J Small Anim Pract 2008;49(2):89-94.
14. Zaidan R, Al Moallem M, Wani BA, et al. Thrombosis complicating high dose intravenous immunoglobulin: report of three cases and review of the literature. Eur J Neurol 2003;10(4):367-372.