Canine autoimmune hemolytic anemia: management challenges

Figures & data

Table 1 Summary of two different prognostic scores developed for use in dogs with immune-mediated hemolytic anemia

Score	Parameter	Definition	Score
CHAOS (Whelan et al)^Citation16	Age	≥7 years	2
	Rectal temperature	≥38.9°C	1
	Persistent agglutination after dilution in saline	Positive	1
	Serum albumin concentration	<30 g/L	1
	Serum bilirubin concentration	≥85.5 µmol/L	2
	Total possible score		7
Ishihara et al^Citation17	Sex	Male	1
	Season	Warm	1
	Packed cell volume	<20%	1
	Platelet count	<200×10^3/µL	1
	Serum total protein concentration	<6 g/dL	1
	Total possible score		5

Abbreviation: CHAOS, canine haemolytic anaemia objective score.

Table 2 Management options for IMHA

Drug or management method	Dose	Mechanism of action	Adverse effects	Cost and practicalities of use
Steroids
Glucocorticoid	Prednisolone: 2 mg/kg/d reducing to 1 mg/kg/d after 2–4 weeks; dexamethasone: 0.2–0.3 mg/kg/d until oral medication can be started	Alters gene transcription; downregulates Fc receptor expression, decreases antigen processing, and suppresses T-cell function	PU/PD, polyphagia, panting, muscle wasting, weight gain, opportunistic infections, GI ulceration, diabetes mellitus, osteoporosis, thromboembolic disease	Inexpensive; 1 mg, 5 mg, and 25 mg tablets available; injectable dexamethasone convenient if vomiting present
Anabolic steroid	Nandrolone: 1–5 mg/kg intramuscularly/subcutaneously, maximum dose 40–50 mg per dog; repeated every 21 days	Thought to stimulate erythropoiesis in nonregenerative anemia; mechanism unproven	Sodium, calcium, potassium, chloride, phosphate retention; water retention; hepatotoxicity, behavioral changes, reproductive abnormalities (oligospermia, estrus suppression)	Parenteral form only; easy to administer; lack of information about efficacy means anabolic steroids are rarely recommended
Steroid-sparing drugs
Azathioprine	2 mg/kg/d po for no more than 14 days; then decrease to 1 mg/kg po every day or 2 mg/kg EOD depending on ease of dosing; or, 50 mg/m^2 every other day	Thiopurine analog	Hepatotoxicity,^Citation28 bone marrow suppression, pancreatitis; most side effects follow use of 2 mg/kg daily dosing for >2 weeks though side effects can occur in dogs that have pre-existing disease in these organs or disease susceptibility	Inexpensive (25 mg and 50 mg tablets); other doses have to be reformulated; do not split tablets; not licensed for use in dogs in the UK
Ciclosporin	2.5–5 mg/kg, po, q12h	Calcineurin inhibitor	GI signs (vomiting, diarrhea, anorexia), gingival hyperplasia,^Citation29 opportunistic infections;^Citation30 ciclosporin is not cytotoxic and is not myelosuppressive as it is specific for lymphocytes	Expensive; capsules available in 10 mg, 25 mg, 50 mg, and 100 mg formulations; liquid formulation available; not licensed for use for this condition but licensed for use in dogs in the UK
Mycophenolate mofetil	10 mg/kg, po, q12h	Purine synthesis inhibitor	GI upset, lethargy, hepatotoxicity, bone marrow suppression	250 mg and 500 mg capsules; available as Cellcept and also in generic form; not licensed for use in dogs in the UK
Leflunomide	1–4 mg/kg, po, q24h	Pyrimidine synthesis inhibitor	GI upset, bone marrow suppression, hepatotoxicity	10 and 20mg tablets Not licensed for use in dogs in the UK
Lithium carbonate	10–11 mg/kg orally, bid	Stimulates erythropoiesis	Diarrhea, hypersalivation, seizures, increased liver enzymes, PU/PD	Little information about use in dogs; serum levels should be measured;^Citation31,Citation32 not licensed for use in dogs in the UK
Rescue therapies
hIVIg	0.5–1.0 g/kg, iv, over 6–12 hours	Fc receptor blockade	Thromboembolic disease, volume overload, anaphylaxis	Expensive; do not repeat infusion; not licensed for use in dogs in the UK
Plasmapheresis	N/A	Microporous membrane separation of plasma from other blood components before immunoglobulins are filtered from plasma to limit immune response	Hypocalcemia due to anticoagulants in circuit	Requires specialist equipment/expertise; limited experience in dogs^Citation33
Splenectomy	N/A	Underlying etiology of IMHA involves antibody-mediated red cell destruction by the spleen; removal of spleen removes site of destruction	Increased susceptibility to infectious agents, risks associated with anesthesia and surgery in a dog with IMHA (thromboembolic disease etc)	One-off surgical and aftercare costs; patient needs to be stabilized for anesthesia – usually requires transfusion

Abbreviations: bid, twice daily; GI, gastrointestinal; hIVIg, human intravenous immunoglobulin; IMHA, immune-mediated hemolytic anemia; N/A, not applicable; po, per os; q12h, every 12 hours; q24h, every 24 hours; EOD, every other day; PU/PD, polyuria/polydipsia; iv, intravenous.

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