Non-regenerative anemia Flashcards
What is the definition of non-regenerative anemia
“Non-regenerative” anemia is characterized by absence of, or sub-optimal, production of new RBCs
What are the two key indicators of a non-regenerative response
The two key indicators of non-regenerative response are:
- an absolute reticulocyte count that is below or within the reference intervals (that persists past when a normal response from the bone marrow would be expected (>5 days))
- an absence of polychromasia on examination of peripheral blood smears
What would be your main differentials for non-regenerative anemia
Anemia of chronic disease
Chronic renal failure
Retroviral infections
Iron deficiency
Pure red cell aplasia
Myelodysplastic diseases
Myeloproliferative diseases
Myelophtisis
Aplastic anemia/pancytopenia
What is anemia of chronic (or inflammatory) disease
This mild to moderate (PCV>15-17%) normocytic, normochromic anemia often accompanies a variety of inflammatory (infectious and non-infectious) and neoplastic diseases in cats
It remains one of the most common causes of non-regenerative anemia in cats
Clinical signs from the anemia itself tend to be mild or absent
What is the main pathophysiological mechanism suspected to be the cause of anemia of chronic disease
The main mechanism is thought to be increased levels of hepcidin
Hepcidin is a peptide produced by the liver that decreases intestinal iron absorption and the release of iron from macrophages
During inflammatory states, interleukin-6 stimulates hepatocytes to release more hepcidin into the blood stream
- the biological rationale for this phenomenon is thought to be the fact that this response reduces the amount of circulating iron that can be utilized by pathogens
Do you know another factor that could play a role in anemia of chronic disease
Overproduction of tumor necrosis factor-alpha is also thought to possibly play a role as it may play an inhibitory role in erythroid differentiation and also a direct inhibitory effect on erythropoietin activity
Explain why chronic renal failure is a cause of non-regenerative anemia
Cats with significant kidney disease can be anemic due to:
- decreased renal EPO production
- bone marrow inhibition by uremic toxins
- decreased RBC survival
- impaired iron utilisation
- blood loss due to GI ulceration or thrombocytopathia if azotemia is severe
Severe anemia from CKD tends to be seen only in IRIS stages 3 or 4
Explain how retroviral infection can lead to non-regenerative anemia
The development of anemia is common in cats with persistent FeLV infection
- often, the anemia is related to bone marrow disorders (e.g., leukemia, myelofibrosis)
- also, anemia of chronic disease may be a big contributor to the hematological picture
What is megaloblastic anemia
Some cats with FeLV infection develop a megaloblastic anemia (characterized by an increased MCV)
What is the suspected mechanism for the aplastic anemia associated with FeLV-C infection
Infection with FeLV subtype C is particularly associated with aplastic anemia
- it is thought that FeLV-C specifically infects erythroid precursors in the bone marrow, affecting heme transport proteins, which leads to fatal heme accumulation in these cells
FeLV and FIV testing can be done on blood and bone marrow samples
How frequent is iron deficiency in cats? What are the possible causes
Iron deficiency anemia is relatively uncommon in cats
It is typically due to chronic blood loss rather than primarilt inadequate intake or absorption
- particularly via the GIT, for example due to a bleeding tumor, or from a heavy flea burden in milk-fed kittens or very elderly patients
How can you differentiate iron deficiency anemia from anemia of inflammation
Decreased reticulocyte hemoglobin content has a high sensitivity and specificity for identifying iron deficiency in cats
Ferritin, the soluble storage form of iron in tissues, is typically decreased in iron deficiency anemia and increased in anemia of inflammation
Transferrin, the main protein that binds and transports iron in blood, is measured indirectly as total iron binding capacity (TIBC)
- TIBC levels are typically normal to increased in cases of iron deficiency
- inflammation can decrease TIBC
Iron saturation percentage (=serum ion/TIBC) < 20% can be suggestive of iron deficiency
What is pure red cell aplasia (PRCA)
PRCA is characterized by a specific deficiency of RBC precursors in the bone marrow
- the granulopoietic and thrombopoietic lines are unaffected
This condition is typically caused by an immune-mediated process directed at early RBC precursors and it should be considered a type of non-regenerative IMHA
What are the two possible type of non-regenerative IMHA
Non-regenerative IMHA may be characterized by:
- “maturation arrest” of erythroid cell lines in the bone marrow (i.e., they get to a certain maturation stage, then stop developing)
- a complete absence of RBC lines (i.e., this scenario is what is seen in PRCA)
What are the key epidemiological facts for PRCA
The disease is uncommon in cats
It typically affects young animals (e.g., up to 3 years of age)
How is PRCA typically characterized
PRCA is typically characterized by a severe (PCV < 7%) normochromic, normocytic anemia
- with WBC and platelet counts either within or above the reference range
What is the treatment of PRCA
Treatment of PRCA is centered around immunosuppressive doses of glucocorticoids
- typically 1-2 mg/kg of prednisolone, PO, q12h
+/- adjunctive immunosuppressants such as cyclosporin or chlorambucil
If responsive, the anemia should resolve within a few weeks
- however, many of these animals need to remain on lonng-term immunosuppression, as relapse is relatively common
