The use of high‐dose immunoglobulin M‐enriched human immunoglobulin in dogs with immune‐mediated hemolytic anemia

Abstract

Background The IV use of human immunoglobulin (hIVIG) in dogs with primary immune‐mediated hemolytic anemia (IMHA) has been described previously, but herein we describe the use of high‐dose IgM‐enriched hIVIG (Pentaglobin). Hypothesis/Objectives Dogs treated with high‐dose Pentaglobin will experience shorter time to remission and hospital discharge and have decreased transfusion requirements compared to dogs receiving standard treatment alone. Animals Fourteen client‐owned dogs diagnosed with primary IMHA at specialist referral hospitals in the United Kingdom. Methods All prospectively enrolled dogs received prednisolone, dexamethasone or both along with clopidogrel. Patients were randomized to receive Pentaglobin at 1 g/kg on up to 2 occasions, or to serve as controls. No additional immunosuppressive drugs were allowed within the first 7 days of treatment. Remission was defined as stable PCV for 24 hours followed by an increase in PCV. Results Ten of 11 dogs from the treatment group and 2 of 3 dogs from the control group achieved remission and survived until hospital discharge. Survival and time to remission were not significantly different between groups. The volume of packed red blood cells transfused, normalized for body weight, was not significantly different between groups. Potential adverse reactions to Pentaglobin occurred in 2 dogs, but their clinical signs may have been related to the underlying disease. Conclusions and Clinical Importance Treatment with high‐dose Pentaglobin was well tolerated by dogs with primary IMHA but no significant advantage was found in this small study. Additional studies examining larger groups and subpopulations of dogs with primary IMHA associated with a poorer prognosis are warranted.

Human intravenous immunoglobulin use for hematological immune-mediated disease in dogs

“…All of the patients that did not survive in this study were humanely euthanized due to ongoing blood transfusion requirements and the financial limitation of continuing treatment. Our results agreed with those of Bestwick et al, 7 which demonstrated no benefit in using an Menriched human immunoglobulin, Pentaglobin, in early treatment for patients with primary IMHA. That study 7 administered hIVIG at a dose of 1 g/kg, a higher dose than the present study, and instituted therapy in an early stage of the disease.…”

“…This study found no specific benefit of such use in the early treatment and response of dogs with IMHA compared to prednisolone alone. 7 Use in ITP has been investigated with a particular interest in reporting platelet recovery times compared to vincristine administration. Most studies found no significant difference between the administration of vincristine versus hIVIG, with the conclusion that vincristine is superior to IVIG in terms of cost, ease of administration, and reduced risk of adverse events.…”

“…Additionally to this mechanism, competitive binding of hIVIG to FcyRIII induces receptor saturation and subsequent antagonism of IgG multimer access, inhibition of dendritic cell maturation, downregulation of proinflammatory cytokines, and many other intricate immunomodulatory mechanisms. 2 In veterinary medicine, available studies report on the use of hIVIG in various diseases, including IMHA, [4][5][6][7][8][9][10][11][12] ITP, 4,5,13,14 Evans syndrome, 4,15 myasthenia gravis, 4 drug-induced cutaneous and immunological reactions, 4,[16][17][18] dermatological disease, 4,19 and sudden acquired retinal degeneration. 4,20 Use in veterinary IMHA and ITP has not been widely studied, and…”

Retrospective analysis of immunosuppressive and anti‐thrombotic protocols in nonassociative immune mediated hemolytic anemia in dogs

“…Time to PCV stabilization was defined as the number of days until the PCV plateaued (±2%) for a period of ≥24 hours, followed by a static or increasing PCV and lack of requirement for additional blood transfusions. 12 Duration of hospitalization was calculated from the day of hospital admittance to the day of hospital discharge. Dogs were considered to have a “relapse” of na‐IMHA when the dog represented to a veterinarian with clinicopathologic changes consistent with suspected or definitive na‐IMHA based on the ACVIM consensus statement, in addition to a reduction in PCV, at a period greater than 2 weeks after the initial diagnosis.…”

“…Immunosuppressive effectiveness was determined based on 4 criteria: (a) time to PCV stabilization, (b) duration of hospitalization, (c) disease relapse, and (d) mortality. Time to PCV stabilization was defined as the number of days until the PCV plateaued (±2%) for a period of ≥24 hours, followed by a static or increasing PCV and lack of requirement for additional blood transfusions 12 . Duration of hospitalization was calculated from the day of hospital admittance to the day of hospital discharge.…”