Canine Immune-Mediated Diseases Study Guide

Overview and Clinical Importance

Immune-mediated diseases of the hemic and lymphatic system represent a significant category of autoimmune disorders frequently encountered in canine practice. These conditions occur when the immune system erroneously targets normal blood components for destruction. The most clinically important immune-mediated hematologic diseases in dogs include Immune-Mediated Hemolytic Anemia (IMHA), Immune-Mediated Thrombocytopenia (ITP), and Evans Syndrome (the concurrent presentation of both conditions). These diseases carry significant morbidity and mortality, with IMHA mortality rates historically ranging from 30-70% despite aggressive therapy.

Immune-Mediated Hemolytic Anemia (IMHA)

Definition and Classification

IMHA is an autoimmune disease characterized by premature destruction of red blood cells (RBCs) due to antibody-mediated mechanisms. It is the most common autoimmune disease in dogs and represents a classic example of a Type II (cytotoxic) hypersensitivity reaction.

Pathophysiology

In IMHA, antibodies (primarily IgG or IgM) bind to antigens on the RBC surface, leading to cell destruction through two primary mechanisms:

Extravascular Hemolysis (More Common)

• Antibody-coated RBCs recognized by Fc receptors on macrophages in spleen and liver
• Partial phagocytosis removes membrane, creating spherocytes
• Results in hyperbilirubinemia (unconjugated) and potential icterus

Intravascular Hemolysis (Less Common, More Severe)

• Complement cascade activation leads to membrane attack complex (MAC) formation
• Direct RBC lysis within the bloodstream
• Results in hemoglobinemia, hemoglobinuria, and potential hemoglobinuric nephrosis

Signalment and Breed Predispositions

Clinical Signs

Diagnosis

There is no single pathognomonic test for IMHA. Diagnosis is based on clinical signs, laboratory findings, and exclusion of other causes of hemolytic anemia.

ACVIM Consensus Diagnostic Criteria

Firm diagnosis requires: At least 2 biomarkers of immune-mediated destruction PLUS at least 1 sign of hemolysis.

Key Laboratory Findings

Complete Blood Count (CBC):

• Moderate to severe anemia (PCV often 10-20%; mean approximately 13-16%)
• Usually regenerative (reticulocytosis, polychromasia, anisocytosis, nucleated RBCs)
• Non-regenerative in approximately 30% of cases (pre-regenerative or precursor-targeted IMHA)
• Spherocytes (small, dense RBCs lacking central pallor) - highly suggestive of IMHA
• Leukocytosis with neutrophilia and left shift (inflammatory leukogram)
• Thrombocytopenia common (70% of cases); suspect Evans syndrome if severe

Saline Agglutination Test (SAT)

The SAT is a rapid, in-clinic test to differentiate true autoagglutination from rouleaux formation:

• Mix 1 drop of EDTA-anticoagulated blood with 4 drops of saline on a glass slide
• Gently rock the slide and observe for macroagglutination (visible speckles/clumping)
• Examine microscopically for microagglutination (grape-like clusters of 4 or more RBCs)

Interpretation: True autoagglutination (immune-mediated) persists after saline dilution, while rouleaux (stacks of coins) disperses with saline.

Treatment

Complications

Pulmonary thromboembolism (PTE) is the leading cause of death in dogs with IMHA, accounting for 30-80% of IMHA-related deaths. Other complications include:

• Disseminated intravascular coagulation (DIC) - occurs in up to 45% of cases
• Acute kidney injury (hemoglobinuric nephrosis)
• Hepatic injury from hypoxia
• Multi-organ dysfunction

Exam Focus: Mortality rates for IMHA remain high (24-52%). Most deaths occur within the first 2 weeks of diagnosis, primarily due to thromboembolism. This underscores the importance of early thromboprophylaxis.

Immune-Mediated Thrombocytopenia (ITP)

Immune-mediated thrombocytopenia (ITP) is an acquired primary hemostatic disorder characterized by immune-mediated destruction of platelets. Antiplatelet antibodies target platelet surface antigens (particularly glycoprotein IIb/IIIa), leading to accelerated removal by macrophages in the spleen and liver.

Signalment

• Age: Middle-aged dogs (median 5-6 years)
• Sex: Female dogs overrepresented (2:1 ratio)
• Predisposed Breeds: Cocker Spaniel, Poodle, Old English Sheepdog

Clinical Signs

Clinical signs reflect primary hemostatic dysfunction. Spontaneous bleeding typically occurs when platelet counts fall below 30,000-50,000/uL:

Treatment

Evans Syndrome

Evans syndrome is defined as the concurrent or sequential occurrence of IMHA and ITP. Approximately 30% of dogs with IMHA will also develop ITP. The condition carries a worse prognosis than either condition alone.

Key Points

• Patients exhibit signs of both anemia AND bleeding/bruising
• Antithrombotic therapy must be carefully weighed (risk of PTE vs. bleeding)
• Cocker Spaniels and Old English Sheepdogs predisposed