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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!

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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
o Prolonged, chronic hemolytic anemia
o Most do not show clinical signs until have
myelofibrosis from “bone marrow burnout” from
chronic hemolysis
o PCR testing available
Phosphofructokinase deficiency (PFK)

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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) ...
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