33 Haematological and haemostatic emergencies

Canine Immune-Mediated Haemolytic Anaemia (IMHA)

Theory refresher

Immune-mediated haemolytic anaemia (IMHA) is the result of red blood cell destruction by the immune system. Red blood cell destruction is initiated by the binding of immunoglobulin G (IgG) or IgM antibodies and complement to their surface. Both extravascular (reticuloendothelial system) and intravascular (causes haemoglobinaemia, haemoglobinuria) haemolysis may occur.

IMHA is generally classified into primary (idiopathic) IMHA, in which no inciting cause is identified, and secondary IMHA, which is associated with an underlying condition (Box 33.1). Primary IMHA is typically diagnosed in young or middle-aged adult dogs but can occur in older dogs too. IMHA is especially common in certain breeds (e.g. English springer spaniel, American Cocker Spaniel). These dogs were previously classified as having primary IMHA although this classification may no longer be appropriate given their genetic predisposition. In dogs with secondary IMHA, the underlying condition may or may not persist at the time of presentation, and may or may not be amenable to specific therapy. In the absence of useful historical information (e.g. with respect to drug administration or vaccination), thorough physical examination, thoracic and abdominal diagnostic imaging, urine microbiology and additional investigations as appropriate are required to rule out an underlying trigger for IMHA.

Hereditary erythrocyte enzyme defects should be kept in mind as possible differential diagnoses in dogs of affected breeds presenting with evidence of haemolytic anaemia. Phosphofructokinase (PFK) deficiency occurs especially in the English springer spaniel, Cocker Spaniel breeds, and mixed breed dogs. Pyruvate kinase (PK) deficiency is most commonly reported in the Basenji as well as in several other breeds including the Beagle, the West Highland White terrier, the Cairn terrier and the miniature poodle.

Treatment

Medical therapy to decrease erythrocyte phagocytosis, complement activation and anti-erythrocytic antibody production is essential for primary IMHA and glucocorticoids are the mainstay of acute therapy. Other immunosuppressive agents may be used in addition to, but not instead of, glucocorticoids (Box 33.2). Immunosuppressive therapy is typically also required for secondary IMHA although success is significantly dependent on whether the underlying condition persists and, if so, whether or not it is amenable to treatment. Clearly with neoplastic conditions in particular, it may not be possible or appropriate to treat the patient.

BOX 33.2 Immunosuppressive agents that may be considered in addition to glucocorticoids in canine immune-mediated haemolytic anaemia (IMHA)

Although there is limited evidence for their efficacy in IMHA, the author typically uses one of these agents in all dogs with primary IMHA in an attempt to allow prednisolone therapy to be tapered more quickly, thereby minimizing side effects. Azathioprine is the cheapest option and is therefore used where possible. However, it likely has the slowest onset of action with a lag of 7–14 days and is therefore started as early as possible. Mycophenolate mofetil and especially ciclosporin are more expensive but may have a quicker onset of action. They are therefore typically only used in cases in which response to glucocorticoids is inadequate. The author has no experience with the use of cyclophosphamide.

Azathioprine: 2 mg/kg p.o. q 24 hr for up to 7–10 days, then q 48 hr long term; monitor for myelosuppression and hepatotoxicity

Mycophenolate mofetil: 10–15 mg/kg p.o. q 12–24 hr

Ciclosporin: 5–10 mg/kg p.o. q 12–24 hr; monitor trough blood concentrations intermittently to achieve effective but safe levels

Dogs with IMHA are at increased risk of thromboembolic complications, especially pulmonary thromboembolism (causes dyspnoea, tachypnoea, cyanosis). Anticoagulant therapy is therefore used in addition to the immunosuppressive therapy. However, there remains much to be clarified with respect to both coagulation abnormalities in IMHA and the most effective preventative and therapeutic treatments. At the time of writing, ultralow dose (0.5 mg/kg p.o. q 24 hr) aspirin therapy is most widely recommended and discontinued at the same time as glucocorticoid administration ceases.

Case example 1

Presenting Signs and Case History

A 4-year-old female neutered English springer spaniel dog presented with a 2-day history of progressive lethargy, exercise intolerance and inappetence. The owner had noticed the dog passing grossly discoloured urine (pigmenturia), prompting emergency presentation. The dog had last received routine annual vaccination 6 months prior to presentation, and there was no recent history of drug administration. There was no notable history of travel and no other significant history was reported.

(Photographs courtesy of Kate English)

Clinical Tip

• In addition to documenting haemolytic anaemia, definitive diagnosis of IMHA requires marked spherocytosis, spontaneous autoagglutination or a positive direct Coombs’ test to be identified. In the author’s experience, most dogs presenting as emergencies with clinically significant IMHA have autoagglutination and/or marked spherocytosis at the time of presentation. The diagnosis can usually therefore be made on an emergency basis without the delay involved in awaiting the results of a Coombs’ test.

In addition to the emergency database, an in-house biochemistry profile was performed that revealed hyperbilirubinaemia (total bilirubin 45 µmol/l, reference range 2–10 µmol/l) and a mild increase in liver enzymes. Free catch urinalysis revealed a specific gravity of 1.050 and dipstick analysis showed 3+ bilirubin and 2+ haemoglobinuria; no bacteria were seen and there was a normal number of white blood cells on sediment examination. In-house blood typing was performed (RapidVet-H Canine DEA 1.1^®; DMS Laboratories, New Jersey, USA) and the dog was successfully typed as DEA 1.1 positive.

Clinical Tip

• Autoagglutination may interfere with blood typing (and crossmatching) which may not therefore be possible. In such cases, packed red blood cells from a DEA 1.1 negative dog should ideally be administered (see Ch. 40).

• If a blood transfusion cannot be performed, Oxyglobin^® (see Ch. 4) may be used instead to provide oxygen-carrying capacity and improve clinical signs while allowing time for medical therapy to take effect. Despite the small bag size of this product, low rates are used (1–2 ml/kg/hr in dogs) which make this a practical option in small and medium size dogs. A total dose of 15–30 ml/kg is administered depending on clinical response, resource availability and financial constraints.