Immune-mediated hemolytic anemia
Immune-mediated hemolytic anemia (IMHA) is a common immune-mediated disease characterized by a type II hypersentivity reaction against erythrocytes. This disease is a common cause of anemia and mortality in dogs.
This disease is caused by the binding of antibodies to the surface of red blood cells as a result of recognition of potentially antigenic RBC membrane proteins, resulting in their phagocytosis within the spleen.
Two forms of IMHA are observed:
- Primary (idiopathic) IMHA - genetic disease commonly reported in middle-aged female American Cocker Spaniels, but also Old English Sheepdog, Poodle and Irish Setter breeds
- Secondary IMHA
- - Anaplasma phagocytophilum
- - Bartonella henselae, B. vinsonii subsp berkhoffii
- - Borrelia burgdorferi
- - Ehrlichia canis
- - Erysipelothrix rhusiopathiae
- - Leishmania infantum
- - Mycoplasma haemocanis
- - Rickettsia rickettsii
- - paraneoplastic syndrome - e.g. associated with sarcomas
- - oxidant agents such as zinc, acetaminophen, onion and garlic
Clinical signs may be initially vague, but lethargy, reduced exercise intolerance, tachycardia and anemia are consistent findings. As the disease progresses, melena, cardiac murmurs, splenomegaly, hepatomegaly, icterus, hemoglobinuria, fever and lymphadenopathy are frequent accompanying signs. Bacteremia is not a feature of this disease.
High mortality rates are observed in the first two weeks following presentation, primarily due to the rapidly escalating anemia, a consumptive coagulopathy and consequential disseminated intravascular coagulation.
Preliminary blood tests usually reveal anemia, haematocrits < 15%, leucocytosis, a left shift and reticulocytosis. The anemia of IMHA is usually regenerative, since erythropoeisis is not adversely affected unless the immune response affects hematopoietic cells. Therefore, reticulocytosis, polychromasia, anisocytosis, and nucleated erythrocytes may be present.
Diagnosis is based on presenting clinical signs of anemia, autoagglutination, the presence of spherocytes on blood smears, a positive gel-based direct agglutination test or Coombs’ test, and the elimination of any other underlying cause of anemia.
Dogs with primary IMHA with ≥ 2 Ig isotypes bound to erythrocytes (tested via direct immunofluorescence), are likely to have a more severe degree of anemia, spherocytosis, and autoagglutination.
A differential diagnosis would include other causes of anemia such as blood loss, splenic torsion, pyruvate kinase deficiency (Basenji), phosphofructokinase deficiency (English Springer Spaniel, American Cocker Spaniel), hereditary osmotic fragility (Alaskan Malamute, Miniature Schnauzer), hemangiosarcoma and hyperadrenocorticism.
The mainstay of treatment involves addressing underlying disease states (especially with secondary IMHA), and use of immunosuppressive drugs to reduced autophagocytosis of erythrocytes.
In severely anemic dogs, oxygen therapy and repeated blood transfusions may also be required.
Prednisolone is given at 2 mg/kg orally every 12 - 24 hours for 1 to 2 weeks, then at a reducing dose over 2 - 4 months.
The combination of prednisolone (2 mg/kg) with azathioprine (2 mg/kg daily) and low dose aspirin (0.5 mg/kg daily) or clopidogrel (0.5 - 1.0 mg/kg daily) appear to have the highest survival rates.
Splenectomy is indicated in non-responsive patients or adverse medication side-effects.
The prognosis with primary IMHA is guarded (25 - 50% mortality rates), despite heightened awareness of the disease and new drug treatment approaches.
Long-term complications of IMHA (due presumably to immunosuppression) are relatively common, and include splenic vein thrombosis, Citrobacter freundii septicemia, gingival overgrowth and periodontitis, and dermatopathies due to Toxoplasma gondii, Alternaria infectoria and Fusarium sporotrichioides and phaeohyphomycosis.
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