Week 1 - Hematology 2 Lecture

DEFINITION OF TERMS
MEGAKARYOPOIESIS
 Production of megakaryocytes
 Maturation series leads to platelet production via platelet shedding
 1 megakaryocyte = 1,000-4,000 platelets
THROMBOCYTES
 Also known as platelets

 Blood cells that maintains blood vessel integrity by initiating vessel wall repairs
ENDOMITOSIS
Form of mitosis with no cytoplasmic division but with nuclear division
PROGENITOR CELLS
 A biological cell that can be further differentiated

 Totipotential hematopoietic stem cell/Totipotent
 Pluripotential hematopoietic stem cell/Pluripotential
1. BFU-Meg (burst-forming unit)
2. CFU-Meg (colony-forming unit)
3. LD-CFU-Meg (light-density CFU)
THREE STAGES OF MEGAKARYOCYTE PROGENITORS
The BFU-Meg clones hundreds of daughter cells through mitosis. The CFU-Meg clones dozens of
daughter cell through mitosis. The LD-CFU-Meg undergoes the first stage of endomitosis. BFU-Meg,
burst-forming unit megakaryocyte, CFU-Meg, colony-forming unit megakaryocyte, CFU-GEMM, colony-
forming unit, granulocyte, erythrocyte, monocyte, megakaryocyte; IL-3, interleukin-3; LD-CFU-Meg, low-
density CFU-Meg; Meg-CSF, megakaryocyte colony-stimulating factor; TPO, thrombopoietin
GROWTH FACTORS
 Started with Myeloid Progenitor Cells which lead to megakaryoblast then to megakaryocyte
 CFU-S become BFU-Meg by the growth factors:
CSF-Meg, TPO and IL-3
 LD-CFU-Meg become Megakaryocyte by the growth factors: TPO, IL-11
Growth factors involved:
1. CSF-Meg
2. CSF-GM
3. FLT3 ligand
4. KIT ligand
5. IL-3
6. IL-6
7. IL-11
8. TPO
PLATELET MATURATION SERIES
1. MEGAKARYOBLAST
 Size: 20 to 50 um in diameter
 Cytoplasm: varying shades of blue, blunt pseudopods, narrow band around the nucleus
 Granules: PRESENT
 Nucleus: single, round, oval kidney shaped
 Chromatin: fine pattern
 Nucleoli: multiple; generally stain blue
 N/C ratio: 10:1
2. PROMEGAKARYOCYTE
 Size: 20-60 um in diameter
 Cytoplasm: more abundant than megakaryoblast, less basophilic
 Granules: bluish, begins to form in the golgi region
 Nucleus: two; irregular in shape
 Chromatin: coarser than previous stage
 N/C ratio: 4:1 to 7:1
 Identifiable as MK-II stage in light microscopy
3. GRANULAR MEGAKARYOCYTE
 Size: 30-90 um
 Cytoplasm: abundant, pinkish blue
 Granules: very fine, numerous granules
 Nucleus: 4 or more; multi-lobed; small in comparison to cell size
 N/C ratio: 2:1
 Identifiable as MK-III stage in 10x magnification
4. MATURE MEGAKARYOCYTE
 Size: 40-120 um in diameter
 Cytoplasm: presence of coarse clumps of aggregated granules
 Granules: numerous aggregated granules
 Nucleus: 8 or more (up to 32)
 Nucleoli: Not visible
 N/C ratio: less than 1:1
FEATURES OF THE THREE TERMINAL MEGAKARYOCYTE DIFFERENTIATION STAGES
MK-I (megakaryoblast) MK-II MK-III (megakaryocyte)

(promegakaryocyte)
% of precursors 20 25 55
Diameter 14-18 um 15-40 um 30-50 um
Nucleus Round indented Multilobed
Nucleoli 2-6 variable Not visible
Chromatin Homogenous Moderately condensed Deeply and variably
condensed
Nucleus-to-cytoplasm 3:1 1:2 1:4
ration
Mitosis Absent Absent Absent
Endomitosis Present Ends Absent
Cytoplasm Basophilic Basophilic and granular Azurophilic and
granular
a-granules Present Present Present
Dense granules Present Present Present
Demarcation system Present Present Present
PLATELET PHYSIOLOGY
Platelets Production:
1. Hematopoietic stem cell

2. Megakaryoblast
3. Megakaryocyte (fragmentation of cytoplasm)
4. Platelets
5. PLATELETS
 Size: 1-3/1-4 um in diameter
 Cytoplasm: light blue to purple; very granular
 MPV: 8 to 10 fL
 Normal value: 150-400x109/L
 Life span: 7-10 days
RODAKS:
The total platelet population turns over in 8 to 9 days (the so-called platelet lifespan)
PLATELET FUNCTION
o Formation of mechanical plug during normal hemostatic response to vascular injury.

o The main steps involved are: adhesion, activation, release, aggregation.
o Platelet must be adequate in number and function to participate optimally in homeostasis.
o The functions of platelets in homeostasis include;
o Maintenance of vascular integrity
o Initial arrest of bleeding by platelet plug formation
o Stabilization of hemostatic plug by contributing to fibrin formation.
PLATELET STRUCTURE
PERIPHERAL ZONE
GLYCOCALYX
o Thickness: 10 to 50 nm
o Contains glycoproteins required for platelet adhesion and aggregation
o Ia, Ib, Ic, IIa, IIb, IIIa, IV, V
o Surface for adherence of coagulation factors
o I, V, VIII, X, XI, XII, XIII
PLASMA MEMBRANE
o Physical and chemical barrier between intra and extracellular environment

o Phospholipids: phosphatidylserine, phosphatidylcholine, phosphatidyl inositol
o Factor VIII (VIII:vWF) – blood coagulation and platelet adhesion
PLATELET ULTRASTRUCTURE
o Glycocalyx is the outer membrane surface. It is rich in glycoproteins, which serve as membrane
receptors.
o Glycoprotein Ib is the receptor for vonWillebrand’s factor (vWF) in the presence of ristocetin.
o Glycoproteins IIb and IIIa are receptors for vWF and fibrinogen and are exposed by stimulation
of thrombin or adenosine diphosphate (ADP).
o cGlycoprotein Va is the receptor for thrombin
OPEN CANALICULAR SYSTEM (OCS)
o Also known as surface connected canalicular system

o Exchange of substances in and out of the platelet
SUBMEMBRANE AREA
o Prevent contact between organelles and cell membrane
o Sub membrane filaments
o Contribute to the normal discoid shape of platelets
o Base for pseudopod formation
o Interact with contractile proteins to modulate platelet adhesion and clot retraction after
activation
SOL-GEL ZONE
o Stable gel component to regulate the arrangement of the internal organelles

o Microtubules: contributes to the discoid shape of an inactivated platelet (discoid)
o Microfilaments: contractile process (changing of shape), 50 nm,
Thrombostenin (actomyosin) – major contractile protein; composed of actin and myosin;15% of
total proteins in platelets
MICROFILAMENTS
ACTIN AND MYOSIN
Actin is the major contractile protein in the platelet cytosol, accounting for 20-30% of the total platelet
protein, where as Myosin composes 2-5% of the total platelet protein.
ACTOMYOSIN AND THROMBOSTHENIN= responsible for clot retraction.
MICROTUBULES
TUBULIN= maintain the shape of platelets
ORGANELLE ZONE
o Metabolic region; granular region

o Alpha-granules, dense granules, mitochondria (10-60 per platelet), peroxisomes
o Dense tubular system (DTS)
 Found in the platelet cytoplasm
 Stored calcium are found
 Synthesis of prostaglandin
PLATELET ULTRASTRUCTURE
o Mitochondria are responsible for energy production.

o Glycogen granules provide energy substrate.
Alpha (α) granules contain contact-promoting factors, including:
Platelet fibrinogen
Platelet-derived growth factor (PDGF)
von Willebrand’s factor (factor VIII:R)
β-Thromboglobulin (BTG)
Platelet factor 4 (heparin-neutralizing)
Fibronectin
Dense granules contain nonprotein factors including:
Adenosine diphosphate (ADP)

Adenosine triphosphate (ATP)
5-Hydroxytryptamine (5-HT; or serotonin)
Calcium
ALPHA GRANULES DENSE GRANULES

Beta thromboglobulin ATP
Platelet Factor 4 ADP
Fibrinogen, Fibrionectin Calcium
Factor 5 Magnesium
PDGF Pyrophosphate
HMWK, Factor VIII: vWF Serotonin
Thrombospondin
1. Plasminogen
2. Alpha-1-antiplasmin
3. C1 esterase inhibitor
Discussion Notes
Megakaryocytes- largest cells in the bone marrow, fragments of it are the platelets
- Megakaryocytopoiesis
- 13 to 15 mm diameter
- Contains nucleus
- Has abundant granules in cytoplasm
Platelets- thrombocytes, repair injuries, biconvex shaped
- Thrombocytopoiesis- platelet shedding
Erythropoietin- growth factor of erythrocytes
Thrombopoietin- growth factor of thrombocytes; produced by the liver and kidneys

Progenitor cells- descendants of stem cells; hard to identify
Endomitosis- only the nucleus undergoes division
Terminal megakaryocyte- produced after endomitosis
Blast- means immature cells
Cyte- means mature cells
Megakaryoblast- also known as MK-I
Demarcation system- system which forms platelets
Thrombocytosis- platelets above normal range
Thrombocytopenia- platelets below normal range (reticulated platelets, stress platelets)
Glycocalyx- produce glycoproteins, absorb albumin and fibrinogen

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DEFINITION OF TERMS

 Also known as platelets

Form of mitosis with no cytoplasmic division but with nuclear division

 A biological cell that can be further differentiated

THREE STAGES OF MEGAKARYOCYTE PROGENITORS

MK-I (megakaryoblast) MK-II MK-III (megakaryocyte)

1. Hematopoietic stem cell

o Formation of mechanical plug during normal hemostatic response to vascular injury.

o Physical and chemical barrier between intra and extracellular environment

OPEN CANALICULAR SYSTEM (OCS)

o Also known as surface connected canalicular system

o Stable gel component to regulate the arrangement of the internal organelles

ACTIN AND MYOSIN

ACTOMYOSIN AND THROMBOSTHENIN= responsible for clot retraction.

TUBULIN= maintain the shape of platelets

o Metabolic region; granular region

o Mitochondria are responsible for energy production.

Dense granules contain nonprotein factors including:

Adenosine diphosphate (ADP)

ALPHA GRANULES DENSE GRANULES

Platelets- thrombocytes, repair injuries, biconvex shaped

- Thrombocytopoiesis- platelet shedding

Erythropoietin- growth factor of erythrocytes

Thrombopoietin- growth factor of thrombocytes; produced by the liver and kidneys

Endomitosis- only the nucleus undergoes division

Terminal megakaryocyte- produced after endomitosis

Blast- means immature cells

Cyte- means mature cells

Megakaryoblast- also known as MK-I

Demarcation system- system which forms platelets

Thrombocytosis- platelets above normal range

Thrombocytopenia- platelets below normal range (reticulated platelets, stress platelets)

Glycocalyx- produce glycoproteins, absorb albumin and fibrinogen

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