nonregenerative anemia

Question 1

What’s the lifespan of normal RBC in circulation for a healthy dog? for a healthy cat?

Answer 1

Dogs: 100 days
Cats: 72 days

Question 2

What’s the role of the reticuloendothelial system (RES)?

Answer 2

it’s responsible for removing injured RBC
- mononuclear phagocytic cells
- in the spleen, liver, LNs

Question 3

What are some reasons for ineffective erythropoiesis?

Answer 3

• absolute or relatively decrease in erythropoietin
• decreased marrow response to the erythropoietin
  - this could also be nutrition deficiency
  - or inflammatory state

Question 4

How is erythropoietin secretion stimulated?

Answer 4

• renal hypoxia = main driver
• then it inhibits the degradation of hypoxia inducible factor (HIF-1)
• HIF-1 then bind to genes that upregulates erythropoietin production
• Erythropoietin production is decreased in AKI and CKD; CKD is a common cause of non-regenerative anemia

Question 5

What’s the most important extra-renal production site of erythropoietin?

Answer 5

liver
- but this is not enough to adequately compensate for lack of renal production
- hypoxia is the stimulus factor for erythropoietin production in the liver – it’s induced by other liver injuries

Question 6

How does inflammation lead to non-regenerative anemia?

Answer 6

cytokines: IL-6, IL-1, TNF-alpha, interferon-gamma –> reduce the production of endogenous erythropoietin
IL-6 also increases production of hepcidin
- hepcidin –> decreases ferroportin (internalization and degradation), which is responsible for export of iron from enterocytes –> iron trapping
- hepcidin also prevent iron release from macrophages & hepatocytes, also block GI absorption of iron –> low blood iron levels, relative iron deficiency
- hepcidin blunts the response to erythropoietin

Question 7

What other nutritional deficiencies can lead to non-regenerative anemia?

Answer 7

• copper –> important for hemoglobin
• vitamin B12 –> inhibits purine and thymidylate synthesis
• folate –> in PEOPLE only - not documented in vet med

Question 8

Elevation in which molecules can lead to non-regenerative anemia?

Answer 8

• parathyroid hormone
• ferritin
• transferrin saturation
• aluminum toxicosis

Question 9

Which drugs can lead to non-regenerative anemia?

Answer 9

• ACEi
• phenobarbital
• cephalosporins

Question 10

How can you differentiate between inflammatory vs iron deficiency non-regenerative anemia?

Answer 10

Serum iron level : low in both
Ferritin - positive acute phase protein: high in inflammation, but not specific (also high in other conditions)
Transferrin - main protein used to transport iron in blood - negative acute phase protein: should be low with inflammation;
- measure total iron binding capacity in vet med
Reticulocytes indices may be a better indicators of iron status

Question 11

What are some bone marrow disorders that can lead to non-regenerative anemia?

Answer 11

• primary medullary disorders, ex pure red cell aplasia
• secondary or extramedullary disorders: myelophthisis
  
  • pyruvate kinase deficiency, estrogen toxicity
  • phenobarbital

Question 12

How is non-regenerative anemia treated?

Answer 12

• iron supplements: PO bioavailability not as well, IM better, still has risk of anaphylaxis
• erythropoiesis stimulating agents: darbepoetin (should consider monthly iron dextran injections at the same time)

For medullary causes of non-regenerative anemia:
- glucocorticoids
- cyclophosphamide 50mg/m2 (for immunosuppression)
- azathioprine
- hydroxyurea (chronic granulocytic leukemia)
- other cytotoxic/ immunosuppressive agents (ex. cytarabine, cyclosporine, combination)

new directions/ others:
- hepcidin antagonists