Immune-Mediated Hemolytic Anemia Study Guide

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IMMUNE-MEDIATED HEMOLYTIC ANEMIA (IMHA)

VMED 7482 Hemolymphatic System

Laura Nafe, DVM, DACVIM (SAIM)

BACKGROUND

• In the normal dog and cat, autoantibodies directed against red blood cell

antigens are identified by the mononuclear phagocyte system in the spleen

and liver, resulting in destruction and removal of senescent (“old”)

erythrocytes.

• Average erythrocyte life span is ~120 days in dogs, ~80-90 days in cats

• IMHA is a pathologic condition resulting in PREMATURE destruction of

erythrocytes due to an inappropriate immune response.

PATHOPHYSIOLOGY

• Type II hypersensitivity reaction

o Anti-RBC antibodies (IgG, IgM)

o Components of the complement system

• Results in premature RBC destruction (hemolysis)

o Many patients have a component of BOTH intravascular and

extravascular RBC destruction (hemolysis)

▪ Extravascular more common than intravascular

▪ Extravascular → mononuclear phagocyte system (spleen, liver)

▪ Intravascular → complement mediated (often assoc with IgM)

• Results in systemic inflammation that can result in any or all of the

following:

o Fever

o Severe neutrophilia (can be as high as 70,000-100,000/uL)

▪ Often have many band neutrophils (1000-8000/uL)

▪ Cats with primary IMHA usually have a normal leukocyte count

o Thrombocytopenia – 25-70% of cases

▪ Usually mild/moderate

▪ Can be severe with concurrent ITP (“Evan’s syndrome”)

o Risk of thromboembolism

▪ Many reasons for a hypercoagulable state (more on pg 13)

o Systemic inflammatory response syndrome (SIRS)

▪ Disseminated intravascular coagulation (DIC): 14-45% of dogs

▪ Multiple organ dysfunction syndrome (MODS)

• Acute kidney injury (AKI)

• Liver disease/dysfunction

▪ Non-cardiogenic pulmonary edema (ARDS/ALI)

• Common in dogs. Rare in cats.

• Can be primary or secondary to other diseases (eg; infection, neoplasia) or

any immune stimulus!

HEMOLYTIC ANEMIA

• IMHA is only ONE cause of hemolytic anemia!

• Other conditions to consider that result in hemolysis, but are NOT immune-

mediated in etiology:

o Microangiopathic or “fragmentation” anemia

▪ Consider diseases that “damage” or cause “shearing” of the RBC

• Large thrombus or DIC

• Hemangiosarcoma

• Vasculitis

• Heartworm caval syndrome

▪ Typical RBC morphology - schistocytes +/- keratocytes

▪ Usually results in consumptive thrombocytopenia

o RBC organisms

▪ These typically result in secondary IMHA

▪ Babesia spp (dogs), Mycoplasma spp (cats>dogs), Cytauxzoon

felis (cats; Missouri/Oklahoma/Arkansas)

o Toxins

▪ Oxidative injury → heinz bodies form → erythrocytes less

deformable → increased fragility → hemolysis

▪ Dogs: Onions, garlic, zinc (penny after 1982, zinc oxide ingestion),

acetaminophen, benzocaine

▪ Cats: acetaminophen, benzocaine

▪ May also see eccentrocytes and occasional spherocytes

▪ NOTE: Other diseases may result in Heinz body formation (eg;

hyperthyroidism), but don’t usually result in Heinz body anemia

o Increased RBC fragility

▪ Hypophosphatemia (typically has to be <1.5)

• Aggressive insulin treatment (DKA)

• “Refeeding syndrome”

▪ Congenital RBC disorders – RARE!

• Pyruvate kinase deficiency (PK)

o English Springer Spaniel, Basenji, Beagle

o Usually diagnosed at 2-4 years of age

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Immune-Mediated Hemolytic Anemia Study Guide