Haematopoietic/Myeloid Growth Factors Flashcards
Erythropoietin is the most important regulator of…
…the proliferation of committed progenitors [Colony Forming Units – CFU- Erythroid (CFU-E)] and their immediate progeny.
Erythropoietin absence leads to…
…severe anaemia.
Erythropoiesis is controlled by
…a highly responsive feedback system in which a sensor in the kidney detects changes in O2 delivery to modulate EPO secretion.
EPO is encoded by a gene on…
…human chromosome 7 expressed primarily in peritubular interstitial cells of the kidney.
EPO contains…
193 amino acids with the first 27 cleaved during secretion.
The final hormone is __. What is the molecular mass?
heavily glycosylated and has a molecular mass of about 30,000 daltons.
Fate of EPO after secretion
It binds on a receptor on the surface of its committed erythroid progenitors in the marrow and is internalized.
Effects of anaemia/hypoxemia on EPO synthesis (Hint: Positive feedback)
It results in increased EPO synthesis (greater than 100 fold). This leads to increased serum level of EPO and consequent stimulation of marrow progenitor cells survival, proliferation and maturation.
The regulated feedback loop of EPO can be disrupted by…
kidney disease, marrow damage or deficiency in iron/essential vitamin.
EPO secretion, Fe delivery and progenitor proliferation are suppressed by
…inflammatory cytokines (produced sequel to infection/inflammatory state.
Epoetin alfa is…
…a recombinant human EPO produced using engineered Chinese hamster ovary cells.
Similarities and differences between EPO and epoietin alfa
It is nearly identical to the endogenous hormone except for differences in carbohydrate modification pattern and potential to cause pure red cell aplasia.
Epoietin alfa has the potential to cause…
pure red cell aplasia.
How was pure red cell aplasia in epoietin alfa observed?
This was observed with a commercially available form associated with development of anti-recombinant EPO antibodies which cross-reacts with endogenous EPO.
Epoietin alfa peparations are supplied in single use vials of what measurement…
2,000 – 4,000 units/mL
What is Darbapoetin Alfa/ Novel Erythropoiesis – Stimulating Protein (NESP)?
A genetically modified form of EPO in which 4 amino acids have been mutated
How does NESP differ from EPO?
Differs for Epoetin in that it is a glycosylated form and exhibits a longer half-life
Half life of NESP
43 h s.c.
Half life of EPO
27 h administered
Therapeutic Uses of EPO Products
Anaemias associated
- poor erythropoietic response e.
- surgery, AIDS, cancer chemotherapy, prematurity and chronic inflammatory conditions (autoimmune disorders e.g. rheumatoid arthritis and systemic lupus erythematosus).
One condition where poor erythropoietin response is observed is…
Chronic kidney disease