IMHA and other regenerative anemia Flashcards
Define anemia.
reduction in circulating RBC, hematocrit, and hemoglobin, leading to a decrease in O2 carrying capacity
- could be due to decreased production, loss, or destruction
How long does RBC differentiation take from the bone marrow?
5-7 days
How quick is reticulocytes noted after acute hemolysis/ hemorrahge?
- 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
What are some differential diagnosis for regenerative anemia?
- 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
What are some ways to differentiate hemorrhage for hemolysis?
- 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
What’s the value of blood smear for anemia?
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
What is osmotic fragility test?
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
What are some signs that raises suspicion for IMHA?
- spherocytosis
- positive osmotic fragility test (85-100% of IMHA cases) – but false positive possible (for other membranous defect disease)
- positive Coomb’s test
What role does direct agglutination test (DAT) have in anemia?
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
What results would be expected for osmotic fragility test and DAT regarding hemophagocytic anemia?
negative for both
What can cause Heinz body anemia?
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
How does hypophosphatemia lead to hemolysis?
- hypophosphatemia decreases RBC ATP storage –> increases fragility
- almost exclusively seen in cats with diabetes mellitus, hepatic lipidosis, and following enteral feeding
What are the 2 most common RBC infection that results in regenerative hemolytic anemia?
Dogs: babesiosis
Cats: hemoplasmosis; cytauxzoonosis causes non-regenerative hemolytic anemia
What’s the presenting signs of canine babesiosis? How is it diagnosed?
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
What’s the presenting signs of feline hemoplasmosis? How is it diagnosed?
- 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
What are some causes of that can increase RBC fragility?
Due to physical trauma to the cells
- abnormal microvascular endothelium
- thrombotic microangiopathies
- canine hemolytic uremic syndrome
- DIC
What are some types of hereditary regenerative anemia?
- 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
What’s the expected results of DAT and OFT for hereditary regenerative anemia?
- DAT negative
- OFT positive/ increased
What’s an example of hemophagocytic regenerative anemia?
hemophagocytic hemangiosarcoma
What are the presenting signs of hemophagocytic hemangiosarcoma? How is it diagnosed?
- weight loss, lethargy anorexia
- splenomegaly
- severe anemia, with thrombocytopenia
- infiltrative disease
- DAT negative usually
- IHC CD11/ CD18
What’s the pathophysiology of IMHA?
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
What are the presenting signs of IMHA?
- 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%
What are some lab tests consistent with IMHA?
- 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
What are some differentials for IMHA?
secondary IMHA - neoplasia, infections, drugs, vaccines?
- if nonregenerative, need to differentia with pure red cell aplasia
How is IMHA treated?
immunosuppression - tapering course of prednisolone (over 2 months)
- relapse possible, even up to 5y
- Thromboprophylaxis: no sufficient evidence to support it
What’s the prognosis of IMHA?
- highest rate of mortality within 2w of diagnosis
- overall 65-75% will survive the first year
- thrombocytopenia may be due to DIC +/- thromboembolism
Describe feline IMHA.
- 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
Describe feline alloimmune hemolysis.
Incompatible blood products used.
- blood transfusion: must type feline blood
- colostrum: if A or AB kitten drinks colostrum from B cat (feline neonatal isoerythrolysis)
