Hematopoietic Growth Factors - Foy Flashcards
What signaling pathway is used to exert erythropoietin’s effects?
What cells are receptive to this factor?
RTK linked to JAK-STAT cascade.
Erythroid precursors in the bone marrow.
Describe the system used to sense hypoxia in order to promote EPO production.
What organs produce EPO?
Normally HIF is a factor that is hydroxylated and proteolytically degraded. In hypoxic conditions, it persists and upregulates genes pertaining to angiogenesis and erythropoiesis.
85% produced in the kidney, 15% in the liver.
What formulations of recombinant EPO are available?
What are their indications?
Epoetin alfa, darbopoietin (longer HL)
For anemias secondary to chronic kidney disease, chemotherapy, MDS, HIV, and premature birth.
What are the side effects of recombinant erythropoietin?
Hypertension
Headache
Venous thrombosis
Cardiovascular disease (increased viscosity!)
Red cell aplasia (rare)
What cells produce thrombopoietin?
Describe the system by which it regulates platelet production.
The liver produces thrombopoietin constitutively.
Circulating platelets and megakaryocytes bind and sequester free TPO (via receptor Mpl). Fluctuations in the amount of platelets increases or decreases the amount of TPO for feedback regulation.
Name two TPO receptor agonists.
What are their indications?
Side effects?
Eltrombopag, Romiplostim
Thrombocytopenias (usually immune).
Headache, venous thrombosis, myelofibrosis.
What cells produce G-CSF?
When?
Produced by monocytes, macrophages, fibroblasts, and endothelial cells.
Increased in inflammatory settings (upregulated by IL-1 and TNF).
Name a recombinant G-CSF.
What are its indications?
Filgrastim
Treatment of fevers & infections, neutropenias, prophylaxis before chemotherapy, etc.
What are Filgrastim’s side effects?
Bone pain > Fever > Fluid retention & edema
Name the growth factor that matches each criterion:
Constitutively expressed and sequestered
Side effects include red cell aplasia
Most common side effect is bone pain
Useful in conjunction with chemotherapy
Thrombopoietin
Erythropoietin (recombinant)
G-CSF (recombinant)
Arguably, all of them.
