Thrombocytopoiesis

Thrombocytopoiesis
❖Megakaryocytopoisesis (thrombopoiesis) is the process
formation of platelets from precursor megkaryoblast stem cells
in bone marrow
❖What are platelets ?
▪ Platelets are formed in the bone marrow by fragmentation of
the cytoplasm of giant cells called “Megakaryocytes”.
▪ Platelets count normally count in PB = 150,000-400,000/µl.
Thrombocytopoiesis
1. Megakaryoblasts (CFU-Meg ):
▪ It is a precursor cell which is originated from committed stem cell
CFU-GEMM and differentiate to a promegakaryocyte, which in
turn becomes a megakaryocyte.
• Megakaryocyte is the beginning of the thrombocytic series.
▪ Megakaryoblast show cytoplasmic granulations
2. Promegakaryocytes:
▪ Promegakaryocytes are larger than their precursor cells because
“endoreduplication happened” i.e. nuclear replication without
dividing of the cell.
• Such replication leads them to attain a larger size.
▪ Their cytoplasm contain basophilic granules.
▪ Process formation of platelets from mrgakaryocyte is still unclear.
• But its thought to be happened that “Megakaryocyte buds off
its cytoplasm to form platelets containing small granules”.
Thrombocytopoiesis
3. Megakaryocytes:
▪ They are the unique cells in that they increase their nuclear
DNA content within the same nucleus of cell
▪ Mean DNA content of megakaryocytes is at least eight times
that of other somatic cells.
▪ One megakaryocyte can produce several thousand platelets.
▪ Their size ranging from 30 – 90 micrometer.
▪ They contain 4 – 16 nuclear lobes.
▪ Their cytoplasm contains many small red-purple granules
▪ Megakaryocytes are mainly found in the bone marrow but
can transit to many organs, including the lung, where part
of the platelet release occurs.
▪ Maturation of megakaryocytes and production of platelets
occurs under the influence of thrombopoietin hormone
Regulation of Thrombopoiesis
Thrombopoietin (TPO) hormones:
▪ A glycoprotein hormone released by the liver, kidney, fibroblast
and endothelial cells
▪ stimulates and regulates the production and differentiation of
megakaryocytes and platelets
▪ The gene for TPO is expressed in the liver, kidney, and to a lesser
extent in stromal cells of spleen and BM
▪ TPO acts together with IL-6 and IL-11 on early megakaryocyte
progenitors as well as mature megakaryocyte
▪ Have a ligand such as myeloproliferative Leukemia (c-MPL)
receptor (CD 110) which is present on early hemopoietic
progenitor cells, megakaryocytes, and platelets.
▪ c-MPL destroyed normally when TPO retain back to its normal
level, thereby reducing megakaryocyte exposure to the TPO
▪ Under physiological conditions, serum levels of TPO are normal
and increased levels in individuals with low platelet counts.
Role of growth factors in Megakaryocytopoiesis
Regulation of Thrombopoiesis cont..
❖ Therefore, the rising and dropping platelets concentrations
regulate
by the Thrombopoietin levels.
❖ Low platelets count lead a higher degree of Thrombopoietin levels
and therefore enhancing higher exposure of undifferentiated bone
marrow cells, leading to differentiation into megakaryocytes and
further maturation of these cells.
❖ On the contrary, high platelet concentrations lead to the reversal of
these physiologic mechanisms. Other factors:
▪ NF-E2 (nuclear factor-erythroid 2): is heterodinamic transcription
factor is thought to be an essential for megakaryocyte maturation
and platelet production
▪ M-CSF and G-SCF: secreted by stromal cells, macrophages and
fibroblasts
▪ Cytokines: IL3, IL6, IL11: secreted by stromal cells,
macrophages and fibroblasts and T cells
Characters of Platelets
❖ Small with 2-3 µm in diameter (i.e. 20% of diameter RBCs)
❖ Shaped like a plate inactive condition
❖ No nuclei (no DNA)
❖ Capable of extravasation and have ameboid motility
❖ Very short lifespan (7-10 days)
❖ Act to form blood clots by altering their plasma membrane
❖ Plays a role in Hemostasis to prevention of blood loss
❖ Activated or stimulated by a breakage or injury in blood vessel
wall
and exposed to collagen fibers,
▪ they turn into a “ stellate” shape which is like a star shape
having rays or projections radiating from the center.
▪ These projecting arms help the platelets to make a plug that
seal the broken blood vessel
Characters of Platelets cont..
Characters of Platelets cont..
Function of Platelets: Hemostasis
❖Whenever a vessel is ruptured, hemostasis is achieved by
several mechanisms;
1. Vascular spasm and platelets activation.
2. Formation of a platelet plug.
3. Formation of a blood clot as a result of blood coagulation.
Function of Platelets: Hemostasis
❖ Hemostasis:
▪ The process of blood clotting and then the subsequent
dissolution of the clot.
Function of Platelets: Hemostasis
❖ During injuries platelets stick to exposed collagen underlying
damaged endothelial cells in vessel wall
❖ Platelet Functions begins with:
1. Adhesion by via glycoprotein (GP) and as soon as activation
occurs (change shape)
2. Started extend projections to make contact with each other
3. Then, release, Thromboxin A2, Serotonin & ADP, von
Wille brand factor (vWF) that cause:
• activating other platelets to adhesion
• vasoconstriction of blood vessels to decreasing blood
flow through the injured vessel.
• ADP is causes platelets stickiness
• vWF is enhanced bind platelets to collagen fibers
4. Aggregation
Function of Platelets: Hemostasis