Podcast
Questions and Answers
Which of the following cytokines is NOT mentioned as working synergistically with TPO?
Which of the following cytokines is NOT mentioned as working synergistically with TPO?
- GM-CSF
- IL-10 (correct)
- KIT ligand
- G-CSF
Platelet Factor 4 (PF4) is known to enhance megakaryocyte growth.
Platelet Factor 4 (PF4) is known to enhance megakaryocyte growth.
False (B)
Name one transcription factor that influences the maturation of megakaryocytes.
Name one transcription factor that influences the maturation of megakaryocytes.
GATA-1
KIT ligand is also known as the ___________ growth factor.
KIT ligand is also known as the ___________ growth factor.
Match the following factors with their effects on megakaryocyte growth:
Match the following factors with their effects on megakaryocyte growth:
What is the normal platelet count range in adults?
What is the normal platelet count range in adults?
Platelets are produced from megakaryocytes in the bone marrow.
Platelets are produced from megakaryocytes in the bone marrow.
What hormone is primarily responsible for regulating platelet production?
What hormone is primarily responsible for regulating platelet production?
The average diameter of normal platelets is ______.
The average diameter of normal platelets is ______.
What is the Mean Platelet Volume (MPV) of normal platelets?
What is the Mean Platelet Volume (MPV) of normal platelets?
Match the following platelet types with their characteristics:
Match the following platelet types with their characteristics:
Synthetic TPO mimetics are used to decrease platelet production in patients with cancer.
Synthetic TPO mimetics are used to decrease platelet production in patients with cancer.
What is the role of MPL in relation to thrombopoietin?
What is the role of MPL in relation to thrombopoietin?
Which of the following TPO mimetics is a nonimmunogenic oligopeptide?
Which of the following TPO mimetics is a nonimmunogenic oligopeptide?
Eltrombopag is effective in treating only chronic immune thrombocytopenic purpura (ITP).
Eltrombopag is effective in treating only chronic immune thrombocytopenic purpura (ITP).
What role does TPO play in thrombocytopoiesis?
What role does TPO play in thrombocytopoiesis?
IL-3 acts in synergy with TPO to induce the early differentiation of ______.
IL-3 acts in synergy with TPO to induce the early differentiation of ______.
Match the following cytokines with their roles in megakaryocytopoiesis:
Match the following cytokines with their roles in megakaryocytopoiesis:
What is the primary use of oprelvekin?
What is the primary use of oprelvekin?
IL-6 and IL-11 work independently of TPO to promote megakaryocyte maturation.
IL-6 and IL-11 work independently of TPO to promote megakaryocyte maturation.
What is the mechanism by which TPO induces the differentiation of megakaryocyte progenitors?
What is the mechanism by which TPO induces the differentiation of megakaryocyte progenitors?
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Study Notes
Platelets (Thrombocytes)
- Trigger primary hemostasis upon exposure to subendothelial collagen and inflammatory proteins during blood vessel injury.
- Derived from megakaryocytes, which are the largest cells in bone marrow, characterized by multiple chromosome copies.
- Normal platelets are nonnucleated, biconvex cells with an average diameter of 2.5 µm and a mean platelet volume (MPV) of 810 fL.
- Typical platelet count ranges from 150-450 x 10^9/L, with women generally having higher counts; two-thirds circulate while one-third is sequestered in the spleen.
- Reticulated (stress) platelets appear as a compensatory response to thrombocytopenia and are larger than normal platelets (> 6 µm) with an MPV of 12-14 fL.
Thrombopoietin (TPO)
- TPO is a glycoprotein growth factor, weighing 70,000 Daltons, with 23% homology to erythropoietin.
- It is primarily synthesized in the liver, kidneys, stromal cells, and smooth muscle; it circulates in plasma as a hormone.
- TPO binds to the MPL receptor on megakaryocytes and platelets, where decreased plasma TPO concentration signals an increase in platelet mass.
- Synthetic TPO analogs such as romiplostim (MPL receptor agonist) and eltrombopag (separately binding MPL site) enhance platelet production, particularly in conditions like chronic immune thrombocytopenic purpura (ITP).
Mechanisms of TPO Action
- TPO plays a crucial role in the differentiation of stem cells into megakaryocyte progenitors, megakaryocyte precursor cells, and ultimately mature megakaryocytes.
- It also promotes the maturation and proliferation of megakaryocytes, driving thrombocytopoiesis (platelet production).
Synergistic Cytokines
- IL-3 works alongside TPO to induce early differentiation of stem cells.
- IL-6 and IL-11, in the presence of TPO, enhance endomitosis and megakaryocyte maturation; oprelvekin (an IL-11 analog) is used to increase platelets in chemotherapy-induced thrombocytopenia.
- Other synergistic factors include:
- KIT ligand (stem cell factor)
- GM-CSF (granulocyte-macrophage colony-stimulating factor)
- G-CSF (granulocyte colony-stimulating factor)
- Acetylcholinesterase-derived megakaryocyte growth stimulating peptide.
Inhibition of Megakaryocytopoiesis
- Factors that inhibit megakaryocyte growth in vitro include:
- Platelet Factor 4 (PF4)
- β-thromboglobulin
- Neutrophil-activating peptide 2
- IL-8
- Transcription factors such as GATA-1, FOG1, and NF-E2 are vital in regulating megakaryocyte maturation, with deficiencies leading to reduced megakaryocytopoiesis.
Regulatory Mechanisms
- An inverse relationship exists between TPO levels and platelet/megakaryocyte mass, indicating that platelet-bound TPO regulates overall platelet count.
- Elevated TPO levels signal a high production demand for platelets, influencing the binding capacity to MPL receptors on megakaryocytes.
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