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Immune-Mediated Hemolytic Anemia
Remo Lobetti, BVSc, MMedVet (Med), Ph.D. Dipl ECVIM (Int Med)

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Introduction
>Destruction or phagocytosis of RBC
>Primary vs. secondary
>Dog - common and often fatal
>Cat - uncommon

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Pathophysiology
>Red cell antibodies
>Primary/idiopathic IMHA:
>Normal erythrocytes
>Secondary IMHA:
>Antigenically altered erythrocytes:
>Exposure of hidden RBC antigens
>Cross reaction with new antigens
>Non-specific antibody reaction

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Immunoglobulins
>IgG and/or IgM antibodies
>IgG antibodies:
>Cannot directly agglutinate RBC unless a large
amount of antibody is present
>Phagocytosed occurs in spleen
>IgM antibodies:
>Direct agglutination of RBC
>IgM can detach after complement activation
and bind to other RBC
>Phagocytosed occurs in liver

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Complement
>Binding of complement proteins to RBC
>Complement activation:
>Intravascular lysis
>Extravascular lysis
>Spherocytes

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Other Factors
>“Membrane attack complex’:
>CI (serine protease)
>Associated with complement cascade
>Damages RBC membrane:
>Influx of water and electrolytes
>Cell swelling
>Lysis
>Phagocytosis by splenic macrophages

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Antibody
Complement
RBC membrane antigen
C3bR
FCR
Macrophage
Spherocyte
Phagocytosed membrane fragment

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Primary IMHA
>Canine:
>Young to middle-aged
>Female spayed
>Specific breeds
>Feline:
>Young
>Male

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Primary IMHA (Cont.)
>No obvious underlying cause
>True idiopathic AIHA
>Can be associated with:
>Evans syndrome
>SLE

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Secondary IMHA Aetiology
>Infectious
>Drugs
>Toxins
>Neoplasia

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Secondary IMHA Infectious
>FeLV
>Bacterial endocarditis
>Ehrlichiosis
>Leptospirosis
>Hemoplasmas
>Babesiosis
>Chronic bacterial infections
>Systemic fungal infections
>Helminths

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Secondary IMHA Drugs
>Penicillin
>Cephalosporin
>NSAIDs
>Potentiated sulphonamides
>Endogenous estrogen
>Vaccines
>Blood transfusions

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Secondary IMHA Toxins
>Beestings
>Snake bites

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Secondary IMHA Neoplasia
>Lymphoma
>Leukemia
>Hemangiosarcoma

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Diagnostic Approach
>History and clinical examination
>Urine and fecal analyses
>Hematology
>Serum biochemistry

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History and Clinical Signs
>History:
>Recent vaccinations
>Exposure tick/parasites
>Recent therapy
>Clinical:
>Anemia
>Hemoglobinuria
>Fever
>Splenomegaly

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Image

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Urine and Fecal Analyses
>Concentrated specific gravity
>Dipstick
>Bilirubinuria
>Hemoglobinuria
>Proteinuria
>Sediment
>RTE cells
>Fecal

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Hematological Findings
>Dependent on onset:
>Inappropriate anemia
>Regenerative anemia
>Spherocytosis
>Inflammatory leukogram
>Thrombocytopenia

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Haematological Findings (Cont.)
>Positive in-saline-agglutination
>Positive Coombs’ test
>Evidence of DIC:
>Prolonged PT/PTT
>Elevated FDP
>Elevated d-dimers

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Antibody-mediated agglutination
Saline added
Gross granularity
Persistent granularity Positive test result
Rouleaux formation
Saline added
Gross granularity
Loss of granularity Negative test result

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Image

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Fc Receptor
Removal of a piece of RBC membrane
Spherocyte
Normal discoid
RBCs

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Biochemistry
> Elevated liver enzymes (ALP/ALT)
> Bilirubinemia
> Elevated urea with normal creatinine
> Elevated proteins

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Diagnostic Approach (Cont.)
>Radiographs
>Abdominal ultrasonography
>Echocardiography
>Urine and blood culture
>Serology and/or PCR
>Bone marrow aspirate/biopsy

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Diagnostic imaging
> Thoracic radiographs
> Spinal radiographs
> Ultrasonography
> Echocardiography

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Summary
>Exclude secondary IMHA before diagnosing primary IMHA
>Early ’80’s – 90% primary IMHA
>Now – 60% primary IMHA

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Therapy
>Treat primary cause
>Immunosuppressive therapy:
>Short course with secondary IMHA
>Prolonged course with primary IMHA
>Supportive therapy

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Corticosteroids
>Decrease Ab production
>Decrease Fc-mediated destruction of red cell
>Prednisone - 2mg/kg bid

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Cyclophosphamide
>Block DNA and RNA synthesis
>Suppress Ab production
>Suppress lymphocytes
>2mg/kg oid 4 days per week

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Cyclosporine
>T-cell suppression
>Inhibition of immune response by decreased production of IL-2
>5mg/kg bid

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Azathioprine
>Suppress T-cell function
>2 mg/kg oid

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Danazol
>Reduces red cell fragility
>Block Fc-receptors
>5-10 mg/kg bid

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Intra-venous Immunoglobulins
>Block/saturate Fc-receptors
>0.5-1.5 g/kg IV over 6 hours

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Other Drugs
>Mycophenolate
>Leflunomide

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Therapeutic Approach
>Prednisone
>Prednisone & azathioprine or cyclophosphamide
>Prednisone & cyclosporine
>Response based on rising Ht

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Treating Tissue Hypoxia
>Blood transfusion:
>Ht
>Acuteness of onset
>Clinical signs of hypoxia
>Products:
>Whole blood
>Packed RBC
>Oxyglobin®
>Blood typing

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Thromboembolism
>Common cause of mortality
>Poor prognosis if occurs
>Causes:
>Increased procoagulant factors
>Decreased anticoagulant factors
>Vasculitis >Enhanced platelet reactivity

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Thromboembolism (Cont.)
>Contributing factors:
>Icterus
>Catheters
>Therapy:
>Heparin 150-200 units/kg tid-qid
>Aspirin 0.5 mg/kg bid
>Clopidogrel?
>Plasma with concurrent DIC

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Supportive Therapy
>Fluids
>Gastric protectants ??
>Specific organ therapy

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