Republic of the Philippines

CAVITE STATE UNIVERSITY

(CvSU)
DON SEVERINO DE LAS ALAS CAMPUS
Indang, Cavite

OVERVIEW
MEGAKARYOPOIESIS
Intended Learning Objectives
After the completion of the chapter, students will be able to:

1. recall the pre-requisite course of the new course.

2. Illustrate the process of megakaryopoiesis

3. explain the mechanism of platelet production and formation.

MEGAKARYOPOIESIS

Historical Review
2nd century
A.D
-hemophilia was first recognized.
12th century
A.D (Moises
Maimonides)
- described 2 male siblings who
died because of excessive
bleeding after circumcision.
 Johann Lukas
Schönlein (1803)
-Clinical description of families with
hemophilia was first published.

-The disorder was given the name

HEMOPHILIA whichmeans “love of
hemorrhage”
1882 Giulio Bizzozero described platelets
1905 Theory on Blood Coagulation by Paul
Morawitz was accepted.
1913 Lee & White WBCT was performed.
1930 Prothrombin time was introduced by Quick.
1940 Other tests for evaluating hemostatic
mechanisms, like plt. Count & BT were
introduced
1964 “Cascade & Waterfall Theory” of coagulation
was introduced.
HEMATOPOIESIS
-Hematopoiesis is the collective term used to described
the process involved in the production of blood cells
from human stem cells (HSCs).
 WHAT IS MEGAKARYOPOIESIS
Production and development of megakaryocytes, the
precursors to platelets.
where?
o In the bone marrow.
o Megakaryopoiesis takes place adjacent to the sinus
endothelium.
o Megakaryocytes protrude through the vascular wall
as small cytoplasmic process to deliver platelets
into the sinusoidal blood.
o maturing cells undergo endomitosis
-Nuclear division, with no cytoplasmic division, resulting to multiple
nucleus

o Growth factor:GM-CSF, IL-3, IL-6, IL-11, KIT

ligand, and TPO.
 GM-CSF Hematopoietic cell growth factor

Proliferation of hematopoietic
IL-3
progenitors

IL-6 Megakaryocyte maturation

a.k.a stem cell factor, mast cell growth factor, and
steel factor
c-kit ligand
- stimulating the cell
to proliferate
-a.k.a MPL ligand
-Major regulator of platelet
formation
THROMBOPOIETIN -95% is produced by the liver
-increases the number and rate of maturation of
megakaryocytes
• Earliest
recognizable stage
under light
microscope
• 14-18 um in
diameter
• N:C ratio is 3:1
• Granules are
absent
• 15-40 um in
diameter
• Nuclear lobulation
begins
• The cytoplasm has
visible bluish-
stained granules
• N:C ratio is 1:2
• Largest cell in BM
• Do not undergo
endomitosis
• Ranging up to 160
μ in size.
• Nucleoli are no
longer visible
• Occasionally
pseudopod/
irregular boarder
• N/C ratio = 1:1-
1:12
• Disintegrated cell
surrounded by
platelet
process when megakaryocytes issuing a long, slender
cytoplasmic processes between endothelial cells and into the sinusoidal
lumen.
7 to 25 per 100x oil
immersion field (x 1000
• Anucleate
magnification) • Diameter: 2-4 µm
• MPV: 8-10 FL
• Shape: disk-
shaped or circular
to irregular,
lavender and
granular under
Wright-stained
wedge preparation
• NV: 150-450 x
109/L
• Very granular
• Life span: 5-10
days
Point of Difference MK IMegakaryoblast MKIIPromegakaryocyte MKIIIMegakaryocyte

% precursors 20 25 55
Diameter 14-18 um 15-40 um 30-50 um
Nucleus Round Indented Multibilobed
Nucleoli 2-6 Variable Not visible
Chromatin Homogenous Condensed Deeply condensed
N:C Ratio 3:1 1:2 1:4
Mitosis Absent Absent Absent
Cytoplasm Basophilic Basophilic and granular Eosinophilic and granular

Alpha granules Present Present Present

Dense granules Present Present Present
DMS(demarcation Present Present Present
System)
highly branched interconnected system of channels that course
through the cytoplasm
CELLULAR ULTRASTRUCTURE

1.
Peripheral Zone 2. 3.
Organelle Zone
Sol-Gel Zone

4.
Membranous System
1. Peripheral Zone
o composed of the membranes and is responsible for platelet
adhesion and aggregation
o Glycocalyx
o Plasma Membrane
o primarily composed of glycoproteins including
factors V, VIII and fibrinogen.
o It is composed of plasma proteins and
carbohydrate molecules that related to the
coagulation, complement, and fibrinolytic
systems.
Plasma Membrane
o Composed of a bilayer of asymetrically distributed phospholipids
embedded with integral protein for surface receptors.
 Glycoprotein
o a.Glycoprotein Ib (GP Ib)serves as the binding site for vWF,
necessary for platelet adhesion
o b.Glycoprotein IIb-IIIa (GP IIb-IIIa; Integrin: αIIbβ3)
is calcium-dependent membrane protein complex for
fibrinogen receptor necessary for platelet aggregation
2. Membranous
System
Dense Tubular System
o Derived from smooth endoplasmic reticulum and sequesters calcium
for platelet activation process
o it is also the site of platelet cyclooxygenase and of prostaglandin
synthesis

Open Canalicular System

o Surface connecting system, an invagination of the plasma membrane
acts as a canal for the release of the granule constituents and
cytoplasm to the exterior of the platelet
3. Sol Gel
o lies directly beneath the platelet membrane and is composed
of:
o Microtubules composed of protein tubulin which
maintains the platelet disc shape
o Microfilaments contain actin and myosin which
upon stimulation of the platelet will interact to form
actomyosin (thrombosthenin) for clot retraction
4. Organelle Zone
o Mitochondria
o for ATP synthesis used for platelet

metabolism
α Granules (most abundant) b. . Dense Granules “SCAAM”
ü Platelet factor 4- heparin neutralizing ü Serotonin
ü β-thromboglobulin ü Calcium
ü Platelet-derived growth factor ü ADP
ü Fibrinogen ü ATP
ü Factor V ü Magnesium
ü vWF
ü Thrombospondin
ü Fibronectin

Lysosomal Granules
ü acid phosphatase
ü hydolytic enzymes
 α Granules (most abundant)
ü Platelet factor 4 heparin neutralizing
ü β-thromboglobulin

ü Platelet-derived growth factor

ü Fibrinogen

ü Factor V

ü vWF

ü Thrombospondin

ü Fibronectin
 b. . Dense Granules “SCAAM”
ü Serotonin ü Vasoconstriction
ü Calcium ü contraction, calcium dependent factors in coagulation
ü ADP (2,7,9,10,Protein C and S)
ü ATP ü For energy
ü Magnesium
 c. Lysosomal Granules
ü acid phosphatase
ü hydolytic enzymes
o Participates in a sequence of events that lead to the formation of a platelet
plug and ultimately to the formation of a stable fibrin clot at the site of vessel
interruption.

a.Primary hemostasis by adhesion, secretion and aggregation with the end view
of hemostatic plug.
b.Blood coagulation by releasing platelet factor 3 that plays a big role in forming
fibrin clot.
c.Clot retraction by its actomysin
d.Helps in localization of bacteria and other small objects and producing
aggregates too large to pass through capillaries.
PLATELET ROLE IN HEMOSTASIS
 Assignment
1.ILLUSTRATE/DRAW THE STAGES OF PLATELET FORMATION (MEGAKARYOPOESIS)

2.DESCRIBE DISTINCT FEATURE FOR EACH STAGES

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