platelet production
TRANSCRIPT
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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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