Canine immune-mediated haemolytic anaemia (IMHA)
IMHA is antibody and/or complement-mediated destruction of red cells, it one of the most common
causes of anaemia in dogs. Red cell destruction occurs by immune mediated extravascular
phagocytosis of opsonised (made more susceptible to phagocytosis) red cells or intravascular
osmotic lysis, both type II hypersensitivity reactions. Either intra- or extravascular haemolysis may
predominate in any one patient or a combination of these two mechanisms. Extravascular
haemolysis by macrophages in the spleen and liver is more common than intravascular haemolysis
that causes haemoglobinaemia and haemoglobinuria. Bone marrow erythroid precursors can also be
targeted instead of or in combination to circulating red cells. This is non-regenerative immunemediated haemolytic anaemia; a more severe disease. Primary IMHA, where no underlying disease is
identified is the most common however IMHA can be secondary to infection, inflammation,
neoplasia (lymphoma, leukaemia, myeloproliferative disease and haemangiosarcoma) and drugs.
English Springer Spaniels and Cocker Spaniels are predisposed to primary IMHA.
Clinical signs
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Lethargy, anorexia
Pallor
Tachycardia, bounding pulses, systolic murmur
Tachypnoea
Jaundice
Hepatosplenomegaly (area where red cells broken down and removed)
Pyrexia
Petechiae (if concurrent immune-mediated thrombocytopenia)
Thromboembolic disease, particularly pulmonary thromboembolism associated with disseminated
intravascular coagulation (DIC) is a recognised complication of IMHA. A hypercoagulable state and
increased aggregability of platelets could be involved with the pathogenesis of pulmonary
thromboembolism.
Diagnosis
Haematology:
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Strongly regenerative anaemia
Spherocytes
Positive in-saline slide agglutination – indicates the presence of haemagglutinating antibody
o A negative test does not rule out IMHA
Left shift neutrophilia
Positive Coombs test – not very reliable, false positives and negatives possible
Serum biochemistry:
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Increased bilirubin
Increased hepatic enzymes
Urinalysis
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Bilirubinuria
Proteinuria
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Haemoglobinuria if intravascular haemolysis
Other tests
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Clotting profile – PT, APTT
Look for underlying disease
o Thoracic CT/radiography
o Abdominal CT/ultrasound
o Infectious disease (Ehrlichia, Anaplasma)
o Urine culture
Treatment
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Immunosuppression – down regulates Fc receptor of expression by phagocytic cells
o Glucocorticoids
 Dexamethasone 0.6mg/kg IV once daily
 Prednisolone 2-4mg/kg daily (divided dose) until PCV normal then reduce
over several months. Reduce by one quarter every 2 weeks in 0.5mg/kg
every other day.
o Azathioprine – onset 10-14 days
o Ciclosporin
o Mycophenolate
Anti-thrombotic treatment
o Low-molecular weight heparin
o Inhibits factor Xa and thrombin
o 80-150IU/kg q6-8hr
Supportive care
o Blood product transfusion if required
o Oxygen therapy
o Appropriate nursing
Prognostic indicators
Retrospective study at University of Utrecht evaluated negative prognostic indicators in primary
IMHA. 149 dogs with HCT < 30%, spherocytosis or positive Coombs test and no evidence of an
underlying disease. Main predictors for mortality in the first 2 weeks after diagnosis were increased
plasma urea concentration, icterus and petechiae (Piek et al., 2008, JVIM).
Canine immune mediated thrombocytopenia (ITP)
In ITP antibodies cause a premature destruction of platelets which results in a significantly shortened
platelet lifespan and thrombocytopenia. The reason for autoantibody production is unknown , the
immune system recognises platelets as foreign antigens. ITP is responsible for approximately 5% of
canine thrombocytopenic patients. In secondary ITP most commonly secondary to infectious agents
or drugs which bind to the platelet and act as haptens. Antibodies are produced against the platelethapten combination. Onset of thrombocytopenia in response to a novel drug occurs at least 1 week
after the drug is started. This can be quicker if the patient has already been sensitised and is reexposed. It is difficult to definitively diagnose drug-induced ITP but it should be expected in any
patient with a sudden, significant drop in platelet following drug exposure.
Differential diagnoses:
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Disseminated intravascular coagulation (DIC)
Neoplasia
Systemic lupus erythematosus (SLE)
Infectious
Haemorrhage
Breed-related
Look for underlying disease. Stop any unnecessary drugs.
Clinical Signs
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Surface or capillary bleeding
Petechiae
Ecchymoses
Melena
Haematuria
Epistaxis
Retinal haemorrhage
Haemoptysis
Haematochezia
Haemarthrosis
Diagnosis
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Ensure thrombocytopenia confirmed by manual platelet count
o Number of platelets per high power field x 15,000
o Check the feathered edge for platelets
o 10-12 platelets per high power field usually indicates adequate platelet numbers
o Primary ITP have lower platelet number than secondary ITP
Anaemia
o Secondary to bleeding
o Concurrent IMHA
Thromboelastography (TEG)
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Assess global haemostasis
Used to assess hypercoaguability or coagulopathy.
Low platelets decrease clot strength and rigidity
 Reduced MA (maximum amplitude) a measure of clot strength
 Reduced G (overall coagulant state)
Treatment
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Supportive care
Cage rest
Minimise trauma/blood sampling
o Only sample peripherally so can apply pressure easily
Blood products
o Fresh whole blood, platelets functional for the first 4 hours post donation
o 10ml/kg will raise recipient’s platelet count by approximately 10x109/L
Immunosuppression
o Prednisolone 2-4mg/kg PO SID
Vincristine
o Stimulates platelet production via megakaryocyte fragmentation and impaired
platelet destruction
o 0.02mg/kg IV
Prognosis
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Platelets counts return to normal within 3-7 days after starting treatment in dogs that
respond to therapy
>70% dogs improve following initial treatment
30% die or PTS
40% relapse