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Anemia, Immune-Mediated Hemolytic 61
• Anecdotal reports in dogs suggest previous ○ Splenomegaly from active phagocytosis Initial Database
and extramedullary hematopoiesis
drug administration (e.g., beta-lactam and • Intravascular hemolysis • CBC with microscopic blood smear
VetBooks.ir IMHA. ○ Binding of IgM and IgG immunoglobulins ○ Decreased hematocrit (HCT), packed cell Diseases and Disorders
evaluation
sulfa antibiotics) may cause a secondary
volume (PCV), RBC count, hemoglobin
to the RBC membrane activates the c′
GEOGRAPHY AND SEASONALITY
membrane with influx of extracellular fluid
In dogs, increased incidence in the spring (40% cascade, causing direct damage to the cell ○ Mild to marked thrombocytopenia
○ Approximately 50% of dogs with IMHA
of cases in May and June) and cell rupture. have a nonregenerative or poorly regenera-
• Potential causes of secondary IMHA in tive anemia at diagnosis.
ASSOCIATED DISORDERS dogs ○ Hallmarks of IMHA: spherocytosis (79%
• Thromboembolism and pulmonary throm- ○ Infectious (ehrlichiosis, babesiosis, ana- of dogs), autoagglutination (42%-66%),
boembolism (PTE) (very common) plasmosis, leptospirosis, dirofilariasis) polychromasia (90%), or some combina-
• Disseminated intravascular coagulopathy ○ Neoplasia (lymphoma, histiocytic sarcoma) tion of these clinical findings in 96% of
(DIC) ○ Drugs (trimethoprim-sulfonamide, penicil- IMHA dogs.
• Thrombocytopenia (<50,000/microL) occurs lin, cephalosporin). ○ Moderate to marked leukocytosis with a
in one-third to one-half of cases (Evans • Autoagglutination (antibody-mediated RBC neutrophilic left shift and/or nucleated
syndrome). clumping), hallmark of IMHA, primarily RBCs.
occurs with IgM coating of RBCs. ○ RBC parasites: Babesia spp (dog), M.
Clinical Presentation • Moderate to marked leukocytosis with a haemofelis (cat), others
DISEASE FORMS/SUBTYPES neutrophilic left shift is common in dogs. • Serum biochemistry
• Primary (idiopathic) IMHA: Immunoglobu- This neutrophilia is likely due to an increased ○ Elevated total bilirubin, liver enzymes
lins attach to antigens or components of the release of cells from the bone marrow during (ALT, alkaline phosphatase [ALP]),
RBC membrane, causing extravascular a strong erythroid response and/or cytokine sometimes blood urea nitrogen (BUN)
hemolysis, intravascular hemolysis, intravas- response to systemic inflammation and/or ○ Artifactual hypophosphatemia (interfer-
cular RBC agglutination, and/or activation necrosis. ence from hyperbilirubinemia)
of the c′ cascade. • Hyperbilirubinemia is associated with ○ Normal total protein with anemia is
• Secondary IMHA: RBCs are destroyed as hemolysis (most common) and decreased consistent with hemolysis.
innocent bystanders in an immune reaction hepatic clearance of bilirubin. • Urinalysis
against antigens or foreign proteins attached • Elevated serum liver enzymes (especially ○ Bilirubinuria and/or hemoglobinuria
to the cell membrane. alanine transaminase [ALT]) suggest hypoxic ○ If pyuria or bacteriuria is present, perform
• Extravascular hemolysis: Immunoglobulin hepatocellular injury. bacterial culture and sensitivity.
or c′-coated RBCs are selectively destroyed • Moderate to marked thrombocytopenia • In cats, FeLV and FIV serologic tests
by macrophages in the spleen and could be due to Evans syndrome or early • Saline agglutination test (slide autoagglutina-
liver. DIC. tion)
• Intravascular hemolysis: c′-mediated RBC • Dogs with IMHA are hypercoagulable and ○ Mix 1 drop of anticoagulated whole blood
membrane damage causes cell rupture. at risk for thromboembolism. Increased with 1 drop of saline on a microscope
liver values, decreased platelet count, and slide.
HISTORY, CHIEF COMPLAINT decreased antithrombin activity are associ- ○ If enough antibodies are present on the
• Signs of anemia: tachycardia, tachypnea, ated with thromboembolism in dogs with cell membrane, RBC agglutination can
dyspnea, lethargy, progressive weakness, collapse IMHA. be identified grossly and microscopically.
• Inappetence, anorexia • Reticulocytosis is more common in dogs at • Coomb’s test (p. 1328), also known as direct
• Vomiting, diarrhea the time of diagnosis than in cats. antiglobulin/antigen test (DAT): perform if
• Discolored urine (bilirubinuria or ○ Absence of reticulocytes: inadequate time no visible autoagglutination
hemoglobinuria) for bone marrow response (3-5 days), and/ ○ Direct Coombs’ test detects antibodies
• Icterus or immune-mediated destruction of RBC attached to RBCs.
• Respiratory distress with acute PTE (p. 842) precursors ○ The sensitivity in IMHA is 60%-89%. A
negative Coombs’ test result does not
PHYSICAL EXAM FINDINGS exclude a diagnosis of IMHA.
• Pale mucous membranes DIAGNOSIS • Coagulation assessment
• Tachycardia ○ DIC (p. 269)
• Tachypnea Diagnostic Overview ○ Hypercoagulability: increased d-dimers
• Bounding pulses The diagnosis is supported by findings of and/or fibrin degradation products (FDPs),
• Icterus anemia, hemolysis (hemoglobinemia or hemo- decreased fibrinogen, decreased antithrombin
• Heart murmur (systolic, left base) globinuria), evidence of antibodies directed • Abdominal radiographs
• Hepatomegaly and/or splenomegaly against RBC (autoagglutination, spherocytosis, ○ Evaluate spleen and liver size.
• If Evans syndrome or DIC, possible petechiae or positive Coombs’ test), and response to ○ Identify an underlying cause for secondary
and/or ecchymosis immunosuppressive therapy. No finding is IMHA.
pathognomonic for primary IMHA, and causes ○ Identify metallic (zinc) gastrointestinal
Etiology and Pathophysiology of secondary IMHA must be investigated as foreign bodies as a cause of non–immune-
• Extravascular hemolysis relevant (e.g., retroviral testing of cats, vector- mediated hemolysis.
○ Commonly occurs in the spleen (occasion- borne disease testing based on geography). • Abdominal ultrasonography
ally liver). ○ Identify an underlying cause (neoplasia)
○ Immunoglobulin (Ig), mainly IgG, Differential Diagnosis of secondary IMHA.
attach to RBC and cause phagocytosis; Anemia: • Thoracic radiographs
minimal c′-mediated cell membrane • Other hemolytic anemias (p. 59) ○ Usually unremarkable; marked pulmonary
damage • Hemorrhage (p. 433) interstitial pattern, patchy alveolar opaci-
○ Partial erythrophagocytosis can cause • Bone marrow disorder, chronic disease ties, and mild pleural effusion might be
spherocytes, a hallmark of IMHA. Icterus (p. 528) associated with a PTE.
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