THROMBOPOIESIS AND

MEGAKARYOPOIESIS

BY
DR. ETU-EFEOTOR T. P.
 Summary

The human platelet produces about 1 x10 11

platelets.

Daily level of production can increase 10-20

fold due to increased demand & an
additional 5-10 fold under stimulation of
exogenous thrombomimetic drugs.
Production of platelets depends on proliferation &
differentiation of haemopoietic stem and progenitor
cells to cells committed to the megakaryocyte
lineage, their maturation to large polypoid
megakaryocytes & their fragmentation into platelets.

External influences that impact megakaryopoiesis &

thrombopoiesis are a supportive marrow stroma,
protein hormones & cytokines e.gs. TPO, SCF, stem
cell derived factor 1, etc.
 Cellular Physiology of Thrombopoiesis.

Platelets form by megakaryocyte membrane

extensions called PROPLATELETS, in a process that
consumes nearly the entire cytoplasmic complement
of membranes, organelles, granules & soluble
macromolecules.

Each megakaryocyte may give rise to 1,000-5,000

platelets before the residual nuclear material is
engulfed by marrow macrophages.
Megakaryocyte development is divided into 4 stages
depending on
1. Quality & quantity of the cytoplasm.
2. Size of the cytoplasm
3. Nuclear lobulation
4. Chromatin pattern of nucleus
Stage 1 megakaryocytes a.k.a. MEGAKARYOBLASTS
account for about 20% of all cells destined to form
platelets.
 WHAT ARE PLATELETS?

Platelets are small, regularly shaped (normally

discoid) clear cell fragments ranging from 2-3 x 0.5
micrometer in diameter i.e. about 20% the diameter
of RBCs and 7-11fL.

The normal platelet count is 150,000 –

400,000/microlitre of blood.

In Nigeria, platelet count 90,000 –

400,000/microlitre of blood.
They are derived from fragmentation of precursor
megakaryocytes.
The average life span of a platelet is just about 7-10
days.
They are shaped like a plate, hence their name; When
activated or stimulated e.g. by a breakage in blood
vessel wall, they turn into a ‘’stellate’’ shape, which is
like a star shape having rays or projections radiating
from the centre. The projecting arms help the platelets
to make a plug to seal the broken blood vessel.
 Sequential access of mechanism.

MULTIPOTENTIAL STEM CELL (haematopoietic

stem cell) MEGAKARYOBLAST
PROMEGAKARYOCYTE
MEGAKARYOCYTE PLATELETS.
 Haematopoietic stem cells:

Haematopietic stem cells are cells found in all

multicellular organisms. They are characterized by
the ability to renew themselves through mitotic cell
division and differentiation into a diverse range of
specialized cell types.
 Megakaryoblasts:

This is a precursor cell to a promegakaryocyte, which

in turn becomes a megakaryocyte. It is the beginning
of the thrombocytic series.

It derives from ‘’ CFU-Meg’’ (megakaryocyte colony

forming units).

Megakaryoblast cells show cytoplasmic granulations.

 Promegakayocytes:

These are larger than their precursor cells b/c of

‘endoreduplication or endomitotic’ division i.e.
nuclear replication without dividing of a cell.
Such replication/division leads them to attain a
larger size.
 Their cytoplasm contain basophilic granules.
The means or process of formation of platelets from
megakaryocytes is still unclear, but it’s thought that
‘’megakaryocyte buds off its cytoplasm to form
platelets’’.
 Megakaryocytes:

These ere unique cells b/c they undergo ‘endomitotic

division’ i.e. they increase their nuclear DNA content
within the same nucleus.
Their size ranges from 30-90 micrometer in
diameter.
They contain 4-16 nuclear lobes.
Their cytoplasm contains many small reddish-purple
granules.
 Mechanism:

Platelets are formed by protrusions into the bone marrow

sinusoids of pseudopods of megakaryocyte cytoplasm,
which detach into the blood stream and fragment to yield
small discoid platelets.
This explains the process of how non-motile platelets,
enter the circulation.
Each megakaryocyte produces about 1000-5000 platelets.
Differentiation of marrow progenitor cells into
megakaryocytes is regulated by the hormone
Thrombopoietin (TPO).
TPO is the major regulator of platelet production
and is produced by the liver and kidneys.

TPO increases the number and rate of maturation of

megakaryocytes via c-MPL receptor.

The means or process of formation of platelets from

megakaryocytes is still unclear.
Though, it’s thought that megakaryocyte buds off its
cytoplasm and gives rise to platelets containing small
granules.
TPO receptor i.e. c-Mpl, is expressed in stem cells,
megakaryocytes and platelet. It signals via the
JAK/STAT family of kinases and transcription
factors.
The role of TPO includes the control of platelet
production, through several chemical messengers,
e.g. The erythroid transcription factor, NF-E2, is an
essential factor for megakaryocyte maturation and
platelet production.
Platelet concentration in blood vessels is regulated
by feedback mechanism i.e. Platelet production is
increased in response to destruction or removal of
platelets and their production decreases in response
to the infusion of platelets.
 Clinical aspects:

Excess production of platelets than normal, results

in thrombosis (blood clot formation), which may
lead to obstruction of blood vessels that may cause
stroke, myocardial infarction, pulmonary embolism,
Deep vein thrombosis, etc.

Platelet number is increased rapidly in severe

haemorrhage.
 Contd:

Main causes of thrombocytopaenia include

1. Failure of platelet production e.gs. Drug toxicity,
viraemia, part of general bone marrow failure, etc.
2. Increased consumption of platelets e.gs
autoimmune, DIC, thrombotic thrombocytopaenic
purpura, etcc.
3. Abnormal distribution of platelets e.g. massive
splenomegaly, hypersplenism, etc.
4. Dilutional loss e.g. massive transfusion of stored
blood to bleeding patients.
 Deficiency effects:

Thrombocytopenia is reduced platelets in blood. It

may lead to easy bruising, excessive haemorrhage
after a cut, heavy menstrual flow, gingival bleeding,
epistaxis, etc.
Mild thrombocytopaenia: platelet count <90x 109/L.
Moderate thrombocytoaenia: platelet count
<50x109/L.
Severe thrombocytopaenia: platelet count
<20X109/L
 Excess production of platelets:

Thrombocytosis is a disorder which is due to

increase in the number of platelets >450X109/L in
peripheral blood.
Causes include:
1. Overproduction of thrombopoietic factors e.gs
TPO, IL-6, cross-reactivity of EPO and TPO
reactors like occurs in iron deficiency anaemia,
haemorrhage.
2. Haematologic malignancies e.gs Myeloproliferative
disesase, etc.
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