IVIG. Intravenous human immunoglobulin (IVIG) (0.5 to 2 g/kg intravenously daily, given over six to 12 hours) has been infrequently used to treat a variety of immune-mediated diseases in dogs, including IMHA. The mechanism of action of IVIG is thought to be a blockade of the Fc receptors on macrophages, thereby reducing phagocytosis of antibody-coated RBCs, interfering with complement, and suppressing antibody production. In addition, IVIG inhibits erythrocyte phagocytosis by binding to canine monocytes and lymphocytes and possibly by an anti-idiotypic down-regulation of antibody production.

IVIG can be given to patients with IMHA as a single infusion or on two or three consecutive days.³⁴ Although IVIG appears to impart short-term benefits (reflected by a rising packed cell volume and reticulocytosis) within days of infusion, long-term benefits were not seen. No complications have been seen with a single IVIG infusion in dogs. Unfortunately, IVIG is also costly and difficult to obtain.³⁰

Liposomal-encapsulated clodronate. Liposomal-encapsulated clodronate (dichloromethylene diphosphonate) is the focus of two studies, one of which is ongoing at Colorado State University.^35,36 Clodronate is a bisphosphonate that, when incorporated into liposomes, is rapidly phagocytized by macrophages leading to apoptosis. Intravenous liposomal-encapsulated clodronate has been shown to significantly reduce the number of canine splenic macrophages and dendritic cells in vitro, thereby obstructing the clearance of antibody-coated RBCs. This reduction, in effect, slows the clearance of opsonized erythrocytes and allows time for the other immunosuppressive drugs to work. The initial study, involving intravenous infusion of liposomal-encapsulated clodronate in healthy dogs and in seven dogs with IMHA, found that the drug is rapid-acting and well-tolerated.³⁵ In that study, results were favorable, and dogs treated with liposomal-encapsulated clodronate in conjunction with prednisone, azathioprine, and heparin demonstrated an improved survival.

Splenectomy is considered one of the last-choice treatments in canine IMHA. The benefits arise from removing one source of B cells and splenic macrophages, the primary culprits in the removal of antibody-coated erythrocytes.²⁴ It is undetermined how effective this procedure is in routine IMHA cases, since only one recent clinical study has been done to assess it as a forerunner of treatment.³⁷ Although this study did show increased survival with splenectomy (58% survival vs. 37.5% in the control group), the sample size was small.

Consider splenectomy only in patients that have not responded to immunosuppressive medications, require high-dose and long-term medications to maintain a remission, or are experiencing severe side effects from medications. As there is a risk of developing marked infection after splenectomy, it is not recommended for patients taking multiple immunosuppressive medications.¹

Treating tissue hypoxia

Patients with IMHA often need oxygen-carrying fluids to support them through the first few days of care until immunosuppression begins to control the disease process. Oxygen alone is rarely beneficial in severe anemia, unless a patient's clinical signs are complicated by thromboembolism. The criteria for transfusion are not rigid but may include the presence of severe tachypnea, dyspnea, tachycardia, cold extremities, weakness, mental depression, or a hematocrit under 15%. If a patient appears comfortable when resting in a cage but becomes agitated and clinically unstable during necessary procedures (radiography or ultrasonography), give a transfusion before proceeding.

The choice of administering packed RBCs, whole blood, or synthetic hemoglobin can be controversial and is often institution-dependent. Ideally, only the necessary component should be given. As transfusion reactions can occur in patients that have not had transfusions previously, crossmatching should be done before transfusion in all non-autoagglutinating patients. Also perform cross-matching in any dog that has received a prior blood transfusion. Since autoagglutination may interfere with accurate blood typing and crossmatching, packed RBCs should only be administered from universal donors (DEA 1-7 negative blood; DEA 4 can be positive) in dogs with IMHA.¹⁵ Administering purified polymerized bovine hemoglobin solution (Oxyglobin—Biopure) can be beneficial in cases in which crossmatching is not possible or compatible blood is not available. Although one study noted that Oxyglobin administration was associated with a poorer prognosis, a more recent study contradicted those findings.^12,29