Scribd
Upload
114 views

Megakaryopoiesis: and Thrombopoiesis

Megakaryopoiesis is the process where stem cells in the bone marrow mature into megakaryocytes through multiple steps of differentiation and endomitosis. Mature megakaryocytes have multiple copies of DNA and produce proplatelets that break off into circulating platelets through thrombopoiesis. Thrombopoietin is the main growth factor that controls megakaryopoiesis and thrombopoiesis. One megakaryocyte can generate up to 5,000 platelets to maintain the normal platelet count and total platelet mass in circulation.

Uploaded by

Iberis
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
114 views

Megakaryopoiesis: and Thrombopoiesis

Megakaryopoiesis is the process where stem cells in the bone marrow mature into megakaryocytes through multiple steps of differentiation and endomitosis. Mature megakaryocytes have multiple copies of DNA and produce proplatelets that break off into circulating platelets through thrombopoiesis. Thrombopoietin is the main growth factor that controls megakaryopoiesis and thrombopoiesis. One megakaryocyte can generate up to 5,000 platelets to maintain the normal platelet count and total platelet mass in circulation.

Uploaded by

Iberis
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
You are on page 1/ 2

Section 2

MEGAKARYOPOIESIS
AND THROMBOPOIESIS

8
PLATELET COUNTING LEARNING GUIDE
DIAGNOSTICS
MEGAKARYOPOIESIS AND THROMBOPOIESIS

Under the control of various growth factors and cytokines, of which thrombopoietin (TPO) is the most
important,5,6 the pluripotent stem cell differentiates into a megakaryoblast by a number of sequential steps.
Intermediate stages are the myeloid stem cell and the committed progenitor cell of the megakaryocytic cell line.
Once the megakaryoblast stage is reached, the cell loses its proliferative capacity and starts its maturation process.
The process of megakaryocyte development and maturation is called megakaryopoiesis.4 Megakaryopoiesis is a
complex, stepwise process that takes place largely in the bone marrow. At the apex of the hierarchy, hematopoietic
stem cells undergo a number of lineage commitment decisions that ultimately lead to the production of polyploid
megakaryocytes. Megakaryopoiesis has a unique way of maturation that does not occur in other cell lineages -
endomitosis: the cell multiplies its nuclear material within the same cell. In other words, endomitosis is nuclear
division without cell division. Eventually maturation results in a mature megakaryocyte, which possesses multiple
DNA copies. The nuclear ploidy of a megakaryocyte is normally between 8N and 64N, while higher and lower
ploidy may occur in pathological conditions.

The final stage of a series of events that commences with the generation of the pluripotent hematopoietic stem
cell in the bone marrow is called thrombopoiesis. It mainly, but not exclusively, occurs through the organization
of cytoplasmic extensions (proplatelets) that fragment and are released as platelets into the bloodstream4 (Figure
5). Depending on the physiological need of new platelets, endomitosis stops and the formation of platelets
commences. It starts with the intracytoplasmic formation of channel-like structures composed of lipids, called the
membrane demarcation system. These lipids later assemble into membrane bilayers and form the cell membranes
of pro-platelets when the megakaryocyte cytoplasm starts to disintegrate. Eventually, megakaryocytes form
pseudopodia-like extensions protruding into sinuses and release platelets into the bone marrow, from where they
rapidly migrate into peripheral blood. A healthy adult produces approximately 1–2 million platelets per second.

Cell volume of megakaryocytes expands in synchronization with nuclear ploidy. Ploidy eventually determines the
number of platelets that a megakaryocyte will produce.5,6 One single mature megakaryocyte can generate up to
5000 platelets. When platelets are released from the megakaryocyte cytoplasm, they still contain small amounts
of nucleic acids. The latter portion represents the youngest platelets in the circulation and is named reticulated
platelets (retPLT), analogous to reticulocytes in erythropoiesis.

It is not precisely known how thrombopoiesis is regulated in humans, but it is generally assumed that TPO plays
a role here. In steady-state conditions, the production of platelets is aimed at keeping the total circulating platelet
mass (Platelet number x Mean Platelet Volume, also called plateletcrit) constant.5 During stress, platelets are
released from megakaryocytes at an earlier stage, which results in larger platelets.

Each individual has their own set point for platelet count and platelet volume; most likely these are under
genetic control and platelet count seems to be tightly regulated under normal conditions.7 As a consequence,
intra-individual variations in platelet count are quite small in comparison with the population reference ranges.
In the normal population, platelet count is inversely correlated with mean platelet volume, and consequently the
total circulating platelet mass is more or less constant among individuals.8

MEGAKARYOCYTE MEGAKARYOCYTE
MEGAKARYOBLAST PROMEGAKARYOCYTE WITHOUT PROPLATELETS WITH PROPLATELETS PLATELETS

MEGAKARYOPOIESIS THROMBOPOIESIS

Figure 5. Megakaryocytes are derived from pluripotential hemopoetic stem cells that have undergone expansion, differentiation and maturation
under the control of the glycoprotein hormone thrombopoietin and other growth factors. Platelets are formed from the cytoplasmic budding of
megakarocytes.

You might also like