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PLATELET PRODUCTIONMEGAKARYOPOIESIS

THROMBOPOIESIS

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Megakaryocyte Progenitors

CFU - GEMM

BFU Meg

CFU Meg

LD CFU - Meg

TPO, Meg CSF, IL-3

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Terminal Megakaryocyte Differentiation

Proliferative phase terminal differentiation

MK-I : megakaryoblast

MK-II : promegakaryocyte

MK-III : mature megakaryocyte

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Features of the Three Terminal Megakaryocyte

Differentiation Stages

MK-I MK-II MK-III

% precursors 20 25 55

Diameter (um) 14-18 15-40 30-50

Nucleus Round Indented Multilobed

Nucleoli 2-6 Variable Not visible

Chromatin Homogenous Condensed Condensed

N:C 3:1 1:2 1:4

Mitosis Absent Absent Absent

Endomitosis Present Ends Absent

Cytoplasm Basophilic Basophilic andGranular

Eosinophilic andGranular

-granules present present present

-granules present present present

DMS present*** present present

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LD-CFU Meg MK-I MK-II MK-III

Proplateletprocesses

Platelet shedding

TPO, IL-1

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Mature Megakaryocyte is confusedwith : Normal osteoclast

Osteoblast

Reticulum cell

Abnormal mutlinucleated erythroblast

Multinucleated plasma cell

Tumor cells Reed-Sternberg cells

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Hormones and Cytokines That ControlMegakaryocytopoiesisTPO IL-3 IL-6 IL-11

Differentiation to progenitors + + 0 0

Differentiation toMegakaryocytes

+ + 0 +

Late Maturation + 0 + +

Thrombopoiesis 0 - + +

Clinical Use + - - +

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Proposed mechanisms of plateletrelease from megakaryocytes

1. Formation of Cell Processes

2. Formation of Demarcation Membrane System

*** 1 megakaryocyte : 1000 5000 platelets(2000-4000)

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Diameter : 1 to 4 um

Thickness : 0.5 1.0 um

MCV : 5 to 7 fL

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PARTS

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1. PLASMA MEMBRANE (Hyalomere)

7.5 nm thickness

Trilaminar unit structure

Glycocalyx (10 to 50 nm)

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2. Submembrane Area

Separates the organelles within the inner matrixof unaltered platelets from the internal side of

the platelet cell wall.

Contains organized system of filaments.

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3. PLATELEL CYTOSKELETON (SOL-GEL Zone)

Represents the matrix of the platelet cytoplasm,circumferential microtubule system and

randomly arranged microfilaments that form anintraplatelet matrix - - - support the plateletdiscoid shape.

Microfilaments : contain significant amount ofTHROMBOSTHENIN

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THROMBOSTHENIN : actin and myosin

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Microtubule system plays an important role inthe contractile response of platelets to

stimulation

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4. ORGANELLES

A. DENSE BODIES

: 250 350 nm in diameter

1. ADP (adenosine diphosphate)

: most important

: binds to specific receptors and initiates

platelet aggregation

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2. ATP

3. Calcium : important in the activation ofmembrane phospholipases

4. Magnesium

5. Serotonin

6. GDP; GTP

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B. ALPHA GRANULES

: 300 to 500 nm

1. Platelet specific protein

*Platelet factor 4 (PF4)

* B Thromboglobulin Family

: bind heparin

*gp IIb/IIIa : receptors for fibrinogen and vWF

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2. Multimerin

3. Adhesive glycoproteins

Fibrinogen

vWF

Fibronectin

ThrombospondinVitronectin

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6. Fibrinolytic Inhibitors2-plasmin inhibitor

PAI 1

7. Membrane Associated ProteinsP-selectinGMP 3324-KD GTP binding proteinGP IV (CD 36)

Osteonectin

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C. LYSOSOMES

: contain acid hydrolases

elastase

collagenase

cathepsin

heparinaseenzymes for polysaccharides

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Life Span

Turnover Rate

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Normally,

The rate of platelet release from megakaryocytesis equivalent to the rate of platelet removal from

the circulation.

Net turnover : 35,000+/-4,300 platelets/mL /day

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2 populations:

YOUNG : hemostatically more effective

OLD : hemostatically less effective

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Life Span

7 10 days / 9-11 days

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