FACTORS THAT AFFECT MEGAKARYOPOIESIS:

1. Hormone: Thrombopoietin (TPO)

 It is a glycoprotein hormone produced mainly by liver, smooth muscle cells, and kidney that regulates
the production of platelets by the bone marrow.

 Stimulates production and differentiation of meg.

It means that from a primitive cell line, TPO affects the growth of megakaryocyte until it becomes a
mature one.

 Has 23% homology with erythropoietin

 Concentration of TPO is inversely proportional with megakaryocyte and platelet mass.

2. Cellular Derived Stimulators: Cytokines

Cytokines are cellular secretions that gives signal in order for the cell to proliferate and differentiate.
Among which are:

 IL3 - acts synergistically with TPO to induce early differentiation of stem cells. Results in the progenitor
lineage.

 IL6 with IL11 - acts in the presence of TPO to enhance the later phenomenon of the following
processes: Endomitosis, Megakaryocyte maturation, and Platelet release/shedding

Different cells produce different cytokines depending on what cell it is: Monocyte produce monokines
and lymphocyte produce lymphokines.

3. Growth Factors

Growth factors are necessary for the growth, maturation and proliferation of megakaryocytes. Among
which are:

 Stem cell factors/Kit Ligand/Mast cell growth factor

 GM-CSF

 G-CSF

 EPO - atleast 20% of circulating epo is needed for meg and platelet maturation
4. Inhibitors of Megakaryopoiesis

Inhibitors control and regulate production of platelet in the circulation because accumulation of platelet
in the blood may lead to formation of thrombus that cuts the oxygen supply in the body causing tissue
necrosis and eventually death.

 Platelet factor 4

 β-thromboglobulin

 NAP2 (Neutrophil activating peptide 2)

 IL8 - the only cytokine that inhibits megakaryopoiesis