PLATELET PRODUCTION

MEGAKARYOPOIESIS THROMBOPOIESIS
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Megakaryocyte Progenitors
CFU - GEMM
TPO, Meg CSF, IL-3

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BFU Meg

CFU Meg

LD CFU - Meg

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Terminal Megakaryocyte Differentiation

Proliferative phase MK-I : megakaryoblast MK-II : promegakaryocyte MK-III : mature megakaryocyte terminal differentiation

Features of the Three Terminal Megakaryocyte Differentiation Stages

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MK-I % precursors Diameter (um) Nucleus Nucleoli Chromatin N:C Mitosis Endomitosis Cytoplasm 20 14-18 Round 2-6 Homogenous 3:1 Absent Present Basophilic

MK-II 25 15-40 Indented Variable Condensed 1:2 Absent Ends Basophilic and Granular

MK-III 55 30-50 Multilobed Not visible Condensed 1:4 Absent Absent Eosinophilic and Granular

-granules
-granules DMS

present
present present***

present
present present

present
present present

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LD-CFU Meg

MK-I

MK-II

MK-III

TPO, IL-1

Proplatelet processes

Platelet shedding

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Mature Megakaryocyte is confused with :

Normal osteoclast Osteoblast Reticulum cell Abnormal mutlinucleated erythroblast Multinucleated plasma cell Tumor cells Reed-Sternberg cells

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Hormones and Cytokines That Control Megakaryocytopoiesis

TPO IL-3 IL-6 IL-11

Differentiation to progenitors Differentiation to Megakaryocytes Late Maturation Thrombopoiesis Clinical Use

+ + + 0 +

+ + 0 -

0 0 + + -

0 + + + +

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Proposed mechanisms of platelet release 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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Phospholipid Constituents
Phosphatidylserine Phosphatidylcholine

Phosphatidylinositol ***vWF : for platelet adhesion

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2. Submembrane Area
Separates the organelles within the inner matrix of 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 an intraplatelet matrix - - - support the platelet discoid shape. Microfilaments : contain significant amount of THROMBOSTHENIN

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THROMBOSTHENIN : actin and myosin

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Microtubule system plays an important role in the 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 of membrane 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 Thrombospondin Vitronectin

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4. Coagulation Factors Factor V Factor XI Protein S 5. Mitogenic Factors Platelet derived growth factor (PDGF) Transforming growth factor B Endothelial Cell Growth Factor Epidermal Growth Factor (EGF)

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6. Fibrinolytic Inhibitors 2-plasmin inhibitor PAI 1

7. Membrane Associated Proteins P-selectin GMP 33 24-KD GTP binding protein GP IV (CD 36) Osteonectin

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C. LYSOSOMES : contain acid hydrolases elastase collagenase cathepsin heparinase enzymes for polysaccharides

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Life Span Turnover Rate

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Normally,
The rate of platelet release from megakaryocytes is 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