IMHA and other regenerative anemia Flashcards

1
Q

Define anemia.

A

reduction in circulating RBC, hematocrit, and hemoglobin, leading to a decrease in O2 carrying capacity
- could be due to decreased production, loss, or destruction

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2
Q

How long does RBC differentiation take from the bone marrow?

A

5-7 days

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3
Q

How quick is reticulocytes noted after acute hemolysis/ hemorrahge?

A
  • aggregates occur within 48h, but this is just a premature release of reticulocytes, not indicating increased production (dogs)
  • release of new reticulocytes takes 2-5 days
  • in cats, punctate reticulocytes can persist for 2-3 weeks in circulation
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4
Q

What are some differential diagnosis for regenerative anemia?

A
  • increased loss (hemorrhage) or increased destruction (hemolysis; IMHA or non-immune mediated destruction)
  • hemorrhage should be readily evident based on PE and history
  • non-immune mediated hemolysis = RBC membrane fragility, infection (Babesiosis, mycoplasma), altered RBC metabolism
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5
Q

What are some ways to differentiate hemorrhage for hemolysis?

A
  • occult GI blood loss may initial be a regenerative anemia, but chronic = non-regenerative due to iron loss
  • once hemorrhage is ruled out, then look for signs of hemolysis
  • Signs of hemorrhage: hemoglobinemia, hemoglobinuria, icterus, yellow feces
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6
Q

What’s the value of blood smear for anemia?

A

Signs of regeneration: reticulocytes, spherocytes, normoblasts, macrocytes with polychromasia, Heinz body formation
- infectious agents: mycoplasma, babesiosis (may need molecular diagnosis in early disease state)
- iron deficiency anemia: hypochromic, microcytic

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7
Q

What is osmotic fragility test?

A

It’s used to differentiate hemolytic vs non-hemolytic disorders
- RBC is incubated in 0.9% and 0.55% NaCl. If there is no colour difference in the supernatant after centrifuge, then it’s negative. It’s positive if the 0.55% one is obviously more red

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8
Q

What are some signs that raises suspicion for IMHA?

A
  • spherocytosis
  • positive osmotic fragility test (85-100% of IMHA cases) – but false positive possible (for other membranous defect disease)
  • positive Coomb’s test
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9
Q

What role does direct agglutination test (DAT) have in anemia?

A

confirms IMHA, if DAT (Coomb’s test) is positive
- it’s not influenced by immunosuppression, or transfusions, or storage
- positive diagnosis of IMHA = DAT positive or spherocytosis

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10
Q

What results would be expected for osmotic fragility test and DAT regarding hemophagocytic anemia?

A

negative for both

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11
Q

What can cause Heinz body anemia?

A

Ingestion of toxins leading to reactive O2 species formation –> denatures hemoglobin –> resulting in Heinz body and methemoglobinemia
- onions
- zinc
- Cats: acetaminophen and methylene blue toxicity (usually has severe anemia)
- Cats: diabetes mellitus, hyperthyroidism, lymphoma – these have only moderate decrease in anemia

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12
Q

How does hypophosphatemia lead to hemolysis?

A
  • hypophosphatemia decreases RBC ATP storage –> increases fragility
  • almost exclusively seen in cats with diabetes mellitus, hepatic lipidosis, and following enteral feeding
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13
Q

What are the 2 most common RBC infection that results in regenerative hemolytic anemia?

A

Dogs: babesiosis
Cats: hemoplasmosis; cytauxzoonosis causes non-regenerative hemolytic anemia

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14
Q

What’s the presenting signs of canine babesiosis? How is it diagnosed?

A

Presenting signs:
- could be vague: fever, lethargy, inappetance
- signs of anemia (tachycardia, tachypnea, rapid heart rate, pale MM, systolic heart murmur), splenomegaly, icterus, red urine

Diagnosis:
- blood smear evaluation
- molecular diagnostics

  • some species of Babesia can lead to antibody formation (gibsoni and vogeli), not canis
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15
Q

What’s the presenting signs of feline hemoplasmosis? How is it diagnosed?

A
  • most common in young (<3y) cats
  • fever, lethargy, decreased appetite
  • signs of anemia, but only a minority will have icterus

Diagnosis:
- blood smear evaluation
- DAT positive, antibody produced after onset of anemia

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16
Q

What are some causes of that can increase RBC fragility?

A

Due to physical trauma to the cells
- abnormal microvascular endothelium
- thrombotic microangiopathies
- canine hemolytic uremic syndrome
- DIC

17
Q

What are some types of hereditary regenerative anemia?

A
  • Pyruvate kinase deficiency
  • phosphofructokinase deficiency
  • both are autosomal recessive
  • both interfere with metabolism
  • large release of iron from hemolysis can lead to myelofibrosis and sclerosis in dogs
18
Q

What’s the expected results of DAT and OFT for hereditary regenerative anemia?

A
  • DAT negative
  • OFT positive/ increased
19
Q

What’s an example of hemophagocytic regenerative anemia?

A

hemophagocytic hemangiosarcoma

20
Q

What are the presenting signs of hemophagocytic hemangiosarcoma? How is it diagnosed?

A
  • weight loss, lethargy anorexia
  • splenomegaly
  • severe anemia, with thrombocytopenia
  • infiltrative disease
  • DAT negative usually
  • IHC CD11/ CD18
21
Q

What’s the pathophysiology of IMHA?

A

Loss of self tolerance to RBC antigens
- tend to be in hypercoagulable state
- thrombocytopenia
- DIC
- hypoxia –> inflammation –> activation of coagulation –> liver necrosis, renal failure
- anemia = central to high mortality risk

22
Q

What are the presenting signs of IMHA?

A
  • median age = 6
  • females, in estrous or whelping; neutered dogs
  • lethargy and loss of appetite; 15-30% will have GI signs (vomiting, diarrhea)
  • signs of anemia (tachycardia, tachypnea, pale MM, systolic heart murmur)
  • yellow/orange tinged feces, red urine = hemolysis
  • Evan’s syndrome (2-5%)
  • splenomegaly, hepatomegaly up to 40%
23
Q

What are some lab tests consistent with IMHA?

A
  • severe anemia
  • marked thrombocytopenia
  • leukocytosis with left shift
  • increased PT, PTT
  • TEG = hypercoagulable, but may not be reliable in severe anemia and hemolysis
  • DAT = positive
  • macroscopic/ microscopic agglutination = suggestive of anemia
  • OFT positive = presence of hemolysis, but doesn’t mean it’s immune mediated
24
Q

What are some differentials for IMHA?

A

secondary IMHA - neoplasia, infections, drugs, vaccines?
- if nonregenerative, need to differentia with pure red cell aplasia

25
Q

How is IMHA treated?

A

immunosuppression - tapering course of prednisolone (over 2 months)
- relapse possible, even up to 5y

  • Thromboprophylaxis: no sufficient evidence to support it
26
Q

What’s the prognosis of IMHA?

A
  • highest rate of mortality within 2w of diagnosis
  • overall 65-75% will survive the first year
  • thrombocytopenia may be due to DIC +/- thromboembolism
27
Q

Describe feline IMHA.

A
  • paucity of info
  • median Hct = 12%, but uncommon to have organ failure and hypercoagulability
  • DAT positive, increased OFT
  • need to ddx from secondary IMHA, which is most likely due to infection: mycoplasma hemofelis, coronavirus, retrovirus
  • if there is persistent evidence of lack of regeneration, consider pure red cell aplasia
  • Tx = similar to dogs, 2m tapering of prednisone
  • Prognosis: mortality rate 24%, 30% may relapse after initial treatment
28
Q

Describe feline alloimmune hemolysis.

A

Incompatible blood products used.
- blood transfusion: must type feline blood
- colostrum: if A or AB kitten drinks colostrum from B cat (feline neonatal isoerythrolysis)