Immune-mediated hemolytic anemia (IMHA) is a life-threatening blood disorder in dogs where the immune system destroys the animal's own red blood cells. It can be either primary (idiopathic) or secondary to underlying causes like infection or vaccination. Diagnosis involves identifying anemia, signs of hemolysis, a positive direct Coombs' test, and ruling out other potential causes. Treatment focuses on immunosuppression using glucocorticoids and other drugs, intensive supportive care, and addressing any underlying triggers. Prognosis is guarded as mortality rates are high, especially early on, though long-term remission is possible with aggressive therapy.
2. Immune-mediated hemolytic anemia (IMHA)
Life threatening disorder
Common in dogs but rare in cats.
Immune-mediated destruction of red blood cells (RBCs) and results in an
accelerated decrease in the total RBC mass.
3. MECHANISM OF DISEASE
The normal life span of the canine RBC is approximately 100 to 120 days.
Removal RBCs by the mononuclear phagocyte system (MPS).
IMHA is a pathologic process that results in premature destruction of RBCs
when an immune response directly or indirectly targets RBCs of all ages.
4. Type II hypersensitivity reaction in which anti-RBC antibodies, including
IgG, IgM, and IgA.
Extravascular hemolysis, Intravascular hemolysis and
Intravascular RBC agglutination.
5. MEMBRANE ATTACK COMPLEX
DIRECT DAMAGE TO CELL
INFLUX OF EXTRA CELLULAR FLUID
HEMOGLOBINEMIA
RUPTURE OF CELL
INTRA VASCULAR HEMOLYSIS
HEMOGLOBINURIA.
6. IgM is better than IgG at fixing complement, intravascular
hemolysis is more likely to occur with IgM-mediated disease.
MPS-mediated process occurs outside of the circulation and is,
therefore, called Extravascular hemolysis
7. FC RECEPTORS BIND TO FC COMPONENT OF RBC
RBC phagocytosis and destruction.
RBC hemoglobin enters the bilirubin metabolic pathway
No hemoglobinemia and hemoglobinuria
8. IMHA can be divided into two main types:
Primary
Secondary
9. Primary (idiopathic) IMHA autoimmune disorder ,predominant form of IMHA
Autoantibodies are produced against the animal’s own RBC membrane antigens.
Glycophorin, targeted by autoantibodies.
10. Secondary IMHA
Immunologic response to nonself antigens that have modified or are associated
with normal RBC membranes.
Secondary IMHA can be caused by a number of underlying processes.
Affected RBCs may become infected by pathogens or coated with foreign
antigen.
11.
12. Vaccination Duval and Giger 1996).
Approximately one quarter of the patients with IMHA in several studies have
been found to be vaccinated within 30 days of presentation.
Alloantibodies.
13. DIFFERENTIAL DIAGNOSIS
Hemolytic anemia in small animals include
Inherited defects,
Toxin exposure,
Hypophosphatemia,
Microangiopathic hemolytic anemia.
Parasitic Disease
14. Hereditary disorder, such as
Pyruvate kinase deficiency (found in basenjis and other canine breeds),
Phosphofructokinase deficiency (found in English springer and American
cocker spaniels), or
Hereditary RBC osmotic fragility (found in Alaskan malamutes and
miniature schnauzers), should be considered.
18. SIGNALMENT
Any canine breed, but cocker spaniels, English springer spaniels, poodles, Old
English sheepdogs, Irish setters, and collies are overrepresented.
American cocker spaniels reportedly represent approximately one-third of all
dogs with IMHA (Giger 2005)
19. >female dogs.
Age of onset ~ 6 years, but IMHA can develop at 1 to 13 years of age.
↑ Warmer months.
21. Physical examination typically reveals:
Pale mucous membranes,
Tachypnea,
Splenomegaly,
Hepatomegaly,
Tachycardia±prominent pulses,systolic heartmurmur or gallop
Icterus,
Pigmenturia (hemoglobinuria or bilirubinuria),
Fever,
Lymphadenopathy
22.
23. Mucous membranes yellow when the serum bilirubin level >2 to 3 mg/dl
Cardiovascular changes, including tachycardia, S3 gallop, and systolic
murmur, are common in anemic patients.
24. A grade II or III of VI systolic hemic murmur is frequently detected in
animals with a packed cell volume (PCV) <15% to 20% and is caused by
anemia-associated blood turbulence.
Approximately 50% to 70% of dogs with IMHA have concurrent
thrombocytopenia known as “Evans syndrome”
25. DIAGNOSIS
Distinguishing between primary and secondary IMHA is crucial for
effective treatment.
The primary disease generally requires aggressive immunosuppressive
therapy.
Secondary IMHA, however, rarely responds well to treatment unless the
underlying cause is eliminated and may even worsen with
immunosuppressive therapy.
26. Adequate criteria for a diagnosis:
Anemia with a hematocrit less than 25% to 30%
Evidence of hemolysis characterized by hemoglobinemia or hemoglobinuria
Evidence of antibodies directed against RBCs, withautoagglutination,
spherocytosis, or positive results from a direct antiglobulin (Coombs’) test
Elimination of other underlying causes of anemia
An appropriate response to immunosuppressive therapy
27. Laboratory Findings
Complete blood count
Erythocyte changes
Anemia (PCV<25%-30%;as low as 6%
Spherocytosis (89%-95% of dogs)
Regenerative response: Polychromasia,
anisocytosis,macrocytosis,nucleated RBCs
50% of dogs have non regenerative anemia.
30. Auto agglutination
Erythocytes coated with high titres of antibody and complement spontaneously
agglutinate
Macroscopic agglutination is visible when blood with a low haematocrit is placed in
EDTA
Microscopic agglutination is evident as small clumps of erythrocytes on stained blood
smear or in a saline wet smear.
31.
32. Slide agglutination test
Differentiates agglutination from rouleaux formation.
Place one drop of EDTA- anticoagulated blood on glass slide with 1-2 drops of saline.
Mix gently.
Evaluate for macroscopic and microscopic agglutination
If microscopic agglutination is present, add a second drop of saline.
If RBCs disperse, the agglutination was due to rouleux formation.
Positive in 40% - 89% of dogs with IMHA.
33.
34.
35. Coomb’s Test
Identifies antierythocyte antibodies or complement on
the erythrocyte
False positive and false negative may occour
There are two types of Coombs’ test:
Direct
Indirect antiglobulin tests
36. The indirect Coombs’ test detects antibodies to RBCs in the serum,
whereas the direct Coombs’ test detects antibodies attached to RBCs.
Patients with IMHA should be tested via the direct Coombs’ test
because the antibodies of most concern are attached to RBCs.
Sensitivity direct Coombs’ test 60 -89% in others.
37. Serum Biochemistry
Hypebilrubinemia (present in 66% of dogs)
Hepatic transaminases (especially ALT) elevated as consequence of hepatic hypoxia
ALP elevated due to cholestatis from MPS hyperplasia or hepatic extramedullary
hematopoieses
Hyper globulinemia
Arterial Blood Gas Evaluation
Profound hypoxemia with normocapnia is consistent with PTE
38. Diagnostic imaging
Abdominal radiographs should be obtained to evaluate spleen and liver size as
well as to detect metallic (zinc) GI foreign bodies and mass lesions.
Chest radiographs may be useful in differentiating patients with primary heart
disease from those with anemia-induced hemic murmurs.
Animals that present with severe tachypnea should be evaluated for pulmonary
thromboembolism, a common complication of the hypercoagulable state
associated with IMHA.
39. BONE MARROW CYTOLOGY
Typically reveals hyperplasia of the erythroid series.
RBC precursors may reveal decreased erythropoiesis or maturation
arrest affecting the erythroid series.
Chronic IMHA may progress to bone marrow damage and secondary
myelofibrosis.
40.
41.
42. Advanced emergency therapy
High-dose human intravenous gammaglobulin,
Plasmapheresis and
Splenectomy.
High-dose human intravenous gammaglobulin,
12 hour intravenous infusion at doses ranging from 0.5 to 1.5 g/kg, without
apparent side effects (Kellerman and Bruyette, 1997; Scott-Moncrieff and
Reagan, 1997)
43.
44. Plasmapheresis
Rapidly removing unbound anti-RBC antibodies from the circulation
Splenectomy:
Major site of RBC destruction in IMHA and is often also an important site of
antibody production, splenectomy can be effective at attaining rapid
remissions in patients with life-threatening disease (Miller, 1992)
45. ANTIBIOTICS
Not routinely used
Avoid sulpha drugs, penicillins and cephalosporins they precipitate
IMHA
Doxycycline is indicated (5-10mg/kg) in tick endemic regions/ treat
susceptible infections.
46. SUPPORTIVE TREATMENT:
Supportive care involves maintenance of organ perfusion hydration and
acid base imbalance.
1.Intravenous fluid therapy
2.Oxygen therapy
3. GI protectants
48. PROGNOSIS
GAURDED
Mortality rate varies from 26%-70%
Anecdotally a 50:50 survival rate is common
Mortality rate highest in the first 2 weeks after diagnosis
Editor's Notes
Not all causes of hemolysis are immune mediated, and non–immune-mediated hemolytic anemia must be differentiated from IMHA.
Leukocytosis with a neutrophilic left shift (leukemoid response) is another common complete blood count finding in dogs with IMHA. Leukocytosis is thought to be caused by a combination of increased marrow release during the strong regenerative erythroid response, cytokine-stimulated myeloid hyperplasia, neutrophil demargination, and decreased migration into poorly perfused necrotic
However, marrow analysis in patients in which the immune response concurrently affects marrow RBC precursors may reveal decreased erythropoiesis or maturation arrest affecting the erythroid series.
SATURATES Fc receptors of the mononuclear phagocytic system with excess donated antibodres, ieavrngfew receptors available to bznd to the patient's own antr-RBC antrbodres attached to the RBC surface membrane.
). The procedure is risky, especially in unstable patients, and response rates are highly unpredictable (Jackson andKmth, 1985), probably because other organs in the MPS (particularly the liver) continue to destroy red cells. Futhermore, for the remainder of their lives splenectomized animals will have anincreased susceptibility to systemic infection and blood-borne parasites such as Huemoburtonella (Thompson, 1995)