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Questions and Answers
What is the primary source of endogenous erythropoietin production?
What is the primary source of endogenous erythropoietin production?
Which hematopoietic growth factor is responsible for stimulating red blood cell production?
Which hematopoietic growth factor is responsible for stimulating red blood cell production?
What is the serum half-life of darbepoetin alfa compared to epoetin alfa?
What is the serum half-life of darbepoetin alfa compared to epoetin alfa?
Which agent is an isoform of erythropoietin covalently attached to a long polyethylene glycol polymer?
Which agent is an isoform of erythropoietin covalently attached to a long polyethylene glycol polymer?
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What can lead to an increased rate of transcription of the erythropoietin gene?
What can lead to an increased rate of transcription of the erythropoietin gene?
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Which hematopoietic growth factor is involved in the proliferation and differentiation of hematopoietic progenitor cells in the bone marrow?
Which hematopoietic growth factor is involved in the proliferation and differentiation of hematopoietic progenitor cells in the bone marrow?
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What is the main mechanism of action of Erythropoietin (EPO)?
What is the main mechanism of action of Erythropoietin (EPO)?
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What is the target hemoglobin level when using Erythropoietin (EPO) for patients with chronic kidney disease?
What is the target hemoglobin level when using Erythropoietin (EPO) for patients with chronic kidney disease?
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What is the usual response to Erythropoietin (EPO) levels in patients with moderate severe anemia?
What is the usual response to Erythropoietin (EPO) levels in patients with moderate severe anemia?
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How does Erythropoietin (EPO) affect patients undergoing myelosuppressive cancer chemotherapy?
How does Erythropoietin (EPO) affect patients undergoing myelosuppressive cancer chemotherapy?
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What is the illegal use of Erythropoietin (EPO)?
What is the illegal use of Erythropoietin (EPO)?
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What is an exception to the relationship between Erythropoietin (EPO) levels and hemoglobin levels?
What is an exception to the relationship between Erythropoietin (EPO) levels and hemoglobin levels?
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What is a potential adverse effect associated with GM-CSF?
What is a potential adverse effect associated with GM-CSF?
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What is the primary difference between G-CSF and GM-CSF?
What is the primary difference between G-CSF and GM-CSF?
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Which clinical condition is G-CSF used for in the context of neutrophil response?
Which clinical condition is G-CSF used for in the context of neutrophil response?
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In hematopoietic stem cell transplantation, what advantage does using peripheral blood stem cells (PBSCs) have over bone marrow stem cells?
In hematopoietic stem cell transplantation, what advantage does using peripheral blood stem cells (PBSCs) have over bone marrow stem cells?
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Which statement regarding GM-CSF is NOT true?
Which statement regarding GM-CSF is NOT true?
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What are the key endogenous regulators of platelet production?
What are the key endogenous regulators of platelet production?
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How is Oprelvekin administered?
How is Oprelvekin administered?
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When is G-CSF or GM-CSF usually administered after completing cancer chemotherapy?
When is G-CSF or GM-CSF usually administered after completing cancer chemotherapy?
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Which of the following is a thrombopoietin receptor agonist?
Which of the following is a thrombopoietin receptor agonist?
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What is the clinical use of pegfilgrastim in cancer chemotherapy-induced neutropenia?
What is the clinical use of pegfilgrastim in cancer chemotherapy-induced neutropenia?
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What does romiplostim not induce antibodies to?
What does romiplostim not induce antibodies to?
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Which type of stem cells can be extracted using G-CSF or GM-CSF?
Which type of stem cells can be extracted using G-CSF or GM-CSF?
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What is the peak platelet response time for Eltrombopag?
What is the peak platelet response time for Eltrombopag?
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Which medication is excreted primarily in the faeces?
Which medication is excreted primarily in the faeces?
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What is a common adverse effect of Interleukin 11?
What is a common adverse effect of Interleukin 11?
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In which condition does Romiplostim increase the risk of progression to acute myeloid leukemia?
In which condition does Romiplostim increase the risk of progression to acute myeloid leukemia?
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What is a common adverse effect of both Eltrombopag and Romiplostim?
What is a common adverse effect of both Eltrombopag and Romiplostim?
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When is Interleukin 11 typically started for thrombocytopenia in patients receiving cancer chemotherapy?
When is Interleukin 11 typically started for thrombocytopenia in patients receiving cancer chemotherapy?
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Study Notes
Haematopoietic Growth Factors
- Haematopoietic growth factors are glycoprotein hormones that regulate the proliferation and differentiation of haematopoietic progenitor cells in the bone marrow.
- Examples of haematopoietic growth factors include erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin 11 (IL-11).
Erythropoietin (EPO)
- EPO is a 34- to 39-kDa glycoprotein produced primarily by peritubular interstitial cells in the kidney.
- Tissue hypoxia leads to increased EPO production, which increases red blood cell production, correcting anemia.
- Examples of erythropoiesis-stimulating agents include:
- Recombinant human erythropoietin (rHuEPO, epoetin alfa)
- Given IV every 3 times a week
- Not cleared by dialysis
- Darbepoetin alfa
- Modified form of erythropoietin with a 2-3 times longer half-life
- Given once a week
- Methoxy polyethylene glycol–epoetin beta
- Isoform of EPO covalently attached to a long polyethylene glycol polymer
- Given IV or SC every 2 weeks or once a month
- Recombinant human erythropoietin (rHuEPO, epoetin alfa)
Mechanism of Action of EPO
- EPO binds to erythropoietin receptors on red cell progenitors, stimulating proliferation and terminal differentiation of erythroid precursor cells.
- EPO also induces the release of reticulocytes from the bone marrow.
Clinical Uses of EPO
- Anaemia secondary to chronic kidney disease
- Improves hemoglobin levels
- Decreases need for blood transfusions
- Improves quality of life
- Patients undergoing myelosuppressive cancer chemotherapy with a Hb less than 10g/dl
Illegal Use of EPO
- By endurance athletes to enhance performance
Response to EPO
- Inverse relationship between EPO level and hemoglobin
- Patients with normal Hb- EPO levels usually less than 20IU/L
- Moderately severe anaemia- EPO usually 100-500IU/L
- Severe anaemia- EPO usually >1,000IU/L
Granulocyte Colony-Stimulating Factor (G-CSF)
- Stimulates proliferation and differentiation of granulocytic progenitor cells
- Mobilizes hematopoietic stem cells, increasing their concentration in peripheral blood
- Used in hematopoietic stem cell transplantation
Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)
- Broader biologic actions than G-CSF
- Stimulates proliferation and differentiation of early and late granulocytic progenitor cells, erythroid and megakaryocyte progenitors
- Stimulates the function of mature neutrophils
- Acts together with interleukin-2 to stimulate T-cell proliferation
- Mobilizes peripheral blood stem cells, but is less efficacious and more toxic than G-CSF
Clinical Uses of G-CSF and GM-CSF
- Cancer chemotherapy-induced neutropenia
- Treatment of neutropenia associated with:
- Congenital neutropenia
- Cyclic neutropenia
- Myelodysplasia
- Aplastic anaemia
- Hematopoietic stem cell transplantation
Adverse Effects of G-CSF and GM-CSF
- G-CSF: bone pain (reversible)
- GM-CSF:
- Fever, malaise, arthralgias, myalgias
- Capillary leak syndrome (peripheral edema & pleural or pericardial effusions)
- Allergic reactions
- Splenic rupture may rarely occur with use of G-CSF for PBSC mobilization
Megakaryocyte Growth Factors
- Thrombopoietin (TPO) and IL-11 are key endogenous regulators of platelet production
- Novel, nonimmunogenic agonists of the thrombopoietin receptor (Mpl) include:
- Romiplostim
- Eltrombopag
- Approved for management of thrombocytopenia
Interleukin 11 (IL-11)
- 65- to 85-kDa protein produced by fibroblasts and stromal cells in the bone marrow
- Oprelvekin is a recombinant form produced by expression in Escherichia coli
- Administered SC, half-life is 7–8 hours
Romiplostim
- Thrombopoietin agonist peptide covalently linked to antibody fragments that extend the half-life
- Administered SC once a week
- Eliminated by the reticuloendothelial system
- Half-life of 3–4 days, inversely related to the serum platelet count
Eltrombopag
- Small nonpeptide thrombopoietin agonist
- Given orally, peak levels in 2–6 hours
- Half-life of 26–35 hours, excreted primarily in the faeces
- Peak platelet response in 2 weeks
Clinical Uses of IL-11, Romiplostim, and Eltrombopag
- IL-11: secondary prevention of thrombocytopenia in patients receiving cancer chemotherapy
- Romiplostim and Eltrombopag: management of chronic immune thrombocytopenia refractory to steroids, immunoglobulins, and splenectomy
Adverse Effects of IL-11, Romiplostim, and Eltrombopag
- IL-11:
- Fatigue, headache, dizziness
- Anemia, dyspnea (due to fluid accumulation in the lungs)
- Transient atrial arrhythmias
- Hypokalemia
- Eltrombopag: hepatotoxicity
- Both:
- Portal vein thrombosis
- Marrow fibrosis (reversible on discontinuation)
- In patients with myelodysplastic syndromes, romiplostim increases the blast count and risk of progression to acute myeloid leukemia
- Rebound thrombocytopenia may occur following discontinuation
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Description
Test your knowledge about haematopoietic growth factors, including erythropoietin, G-CSF, GM-CSF, IL-11, and thrombopoeitin. Learn about the role of these glycoprotein hormones in regulating hematopoietic progenitor cells in the bone marrow.
