IMHA treatment's first goal to improve oxygen delivery to cells

IMHA treatment's first goal to improve oxygen delivery to cells

Jan 01, 2007

Q: Please review the management of immune-mediated hemolytic anemia.

A: Dr. Douglass K. Macintire at the 2006 American College of Veterinary Internal Medicine Forum in Louisville, Ky., gave a lecture on new therapies for immune-mediated hemolytic anemia (IMHA). Some relevant points from this lecture are outlined in this article.

IMHA is caused by the production of antibodies against red blood cells, resulting in the premature destruction of erythrocytes, which leads to clinically significant hemolytic anemia. Clinical signs include lethargy, weakness, anorexia, pale mucus membranes, icterus, pyrexia, vomiting, systolic murmur, tachycardia, hepatomegaly, splenomegaly and mild lymphadenopathy. The diagnosis is usually made by finding a positive Coombs' test, autoagglutination when blood is mixed with an equal volume of saline, and the presence of spherocytes on the blood smear. Other causes of hemolytic anemia—such as hematogenous parasites, toxins, metabolic derangements (hypophosphatemia, hypotonicity or severe acidosis), mechanical damage to red blood cells and genetic defects—should be ruled out with history and diagnostic testing.

Current treatment protocols are based mostly on subjective information and are modified as new information is obtained from research findings and retrospective studies. This discussion will summarize some of the newer ideas in treatment of this acute, life-threatening disease.

Treatment goals

The first goal of IMHA treatment is to improve oxygen delivery to cells to prevent the terrible consequences of multiple organ dysfunctions. In anemic animals, the best way to improve oxygen delivery to cells is to increase the hemoglobin concentration of the blood. In the past, veterinarians have avoided blood transfusions so they wouldn't "add fuel to the fire." Now realized is that poor oxygenation can result in liver failure, coagulation activation, release of inflammatory cytokines, endothelial damage, myocardial depression and initiation of the systemic inflammatory response syndrome.

Rather than let an animal remain severely anemic (PCV <12%) for prolonged periods, most veterinarians prefer to maintain the hemoglobin between 7-10 g/dl and the hematocrit between 20-30 percent. This goal can be achieved through the administration of purified bovine hemoglobin (Oxyglobin®), packed red cells or stored whole blood. Some veterinarians prefer to use Oxyglobin initially in dogs with severe autoagglutination in the hope that a blood transfusion will be better tolerated after several days of immunosuppressive therapy. The dose of Oxyglobin is 15 ml/kg over three hours given twice daily. Once autoagglutination begins to resolve, a transfusion of packed red cells can be given at a dosage of 10-15 ml/kg over four hours. Whole blood can be used instead of packed red cells, but it is more likely to cause volume overload because it contains plasma as well as red blood cells. Dogs with hemolytic anemia have normal plasma protein levels despite reduced red cell mass. It is not necessary to crossmatch a dog that has never been transfused, since dogs do not have naturally occurring antibodies against red blood cell antigens. If the dog has been previously transfused more than five days earlier, blood must be crossmatched before transfusion to avoid serious reactions.

The second goal of IMHA treatment is to provide adequate perfusion in order to promote tissue oxygenation, avoid capillary stasis that predisposes to thrombosis, and provide for diuresis of hemoglobin from lysed cells. In the past, veterinarians avoided intravenous catheters in animals with IMHA because of concern that they might predispose the animal to thrombosis. Many animals with IMHA have nausea, anorexia and vomiting, leading to the potential for dehydration and electrolyte and acid-base abnormalities. In the past, veterinarians also worried that intravenous fluids would dilute the hematocrit even lower. This is not a concern if hemoglobin levels are maintained with Oxyglobin or transfusions. Animals that have autoagglutination, dehydration, capillary stasis and poor perfusion are at risk for thrombosis and should receive intravenous fluids. Once dehydration is corrected, fluids should be administered at 1- to 1.5-times maintenance rate until the animal is eating and drinking, and autoagglutination is no longer present.

The third goal of IMHA treatment is immunosuppression. Glucocorticoids remain the mainstay of treatment despite the common side effects of polyuria, polydipsia, polyphagia, weight gain, hair loss, panting and urinary incontinence. Initial treatment begins with prednisone (2.2 mg/kg PO q 2 h) until the hematocrit reaches 25-30 percent. The dose is gradually tapered by approximately 25 percent (q 2-3 weeks) until a dose of 0.5 mg/kg PO q 48 hrs is reached. Some dogs must remain on low-dose prednisone for life to avoid relapses. In dogs that are vomiting, injectable dexamethasone (0.3 mg/kg IV q 12 h) can be used. The dose is much lower than the prednisone dosage because dexamethasone is seven to 10 times more potent.