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FACULTY OF MEDICINE
HEMATOLOGY DEP.
PRESENTATION:
PLATELETS & PLATELETS
DISORDERS
AYMEN OMER
NO
SHAPE
SIZE
STRUCTURE
MEMBRANE
RECEPTORS
ENZYMES
PROTIENS
HORMONES
PLATELETS
OVERVIEW
OVERVIEW
Platelets
Small
granulated
Non-nucleated
round or oval
2 4 in diameter
150000 450000/mm
Thrombopoietin
(THPO)
Megapoietin
MGDF
MPl ligand
fibroblasts
endothelial cells
certain leucocytes
Normally
25 40 % of platelets are
present in the spleen
tructure of platelets
Granules
Mitochondria
Golgi zone
Glycogen
Microtubules
Dense
body
Membrane
Dense
tubular
System
Microfilament
Dense body in
granule
Open canalicular
system
Structure of platelets
- Plasma membrane
*** plasma membrane contains
Phospholipids
glycoprotein receptors
Include
For
platelet factor 3
collagen
Accelerate clotting
reactions.
fibrinogen
vessel von-Willebrand Form precursors for
factor
thromboxane A
***
The
plasma
membrane
invaginates into the interior
of the platelets to form the
open canalicular system
serves as a pathway
uptake
of
extra cellular
calcium
release
intracellular
substances
of
II Platelet cytoplasm
1- Contractile proteins
actin
thrombosthenine
myosin
3- Residuals of
endoplasmic reticulumGolgi apparatus
Synthesis
of enzymes
Calcium
store
8- 2 types of granules
A) Dense
granules
b) Alpha granules
contain the
secreted proteins
clotting factors
fibrin
stabilizing
factor
XIIIderived
platelet
growth factor
Plasma Membrane:
Platelet Adhesion
Adhesion Initial response to vessel wall injury
Independent of platelet activation
Passive (no energy required) Does not
require Ca2+
Mechanism of platelet adhesion Exposure of
subendothelium
vWF:GPIb/IX interaction mediates binding to
collagen at high shear rates
Gp Ia/IIa and GPVI mediate direct binding to
collagen at low shear rates
vWF induces signaling events that
include: a. cytosolic Ca2+
b.Activation of protein kinase C (PKC)
c.Phosphorylation events
Platelet Secretion
Platelet secretion ATP required for
centralization of organelles
Release of granule contents into OCS
Recruitment and activation of
additional platelets from the circulation
Released products promote
secondary hemostasis and repair
ADP, serotonin platelet activation
Ca2+ activation, assembly of
plasma coagulation factors
Growth factors & mitogens
stimulate vessel wall repair
Platelet Aggregation
Platelet aggregation is
absolutely dependent on
activation of GPIIb/IIIa
receptor complex
Primary functions of
GPIIb/IIIa Receptor for
fibrinogen (low shear)
vWF (high shear)
Requires Ca2+ + ATP
Activation upregulation of GPIIb/IIIa
receptors on to the
platelet membrane
Triggered by a
number of agonists
ADP, TXA2, Collagen,
Epinephrine, Thrombin,
Arachidonic Acid
GPIIb/IIIa
Platelet Aggregation
Agonists Collagen, thrombin,
arachidonic acid
Stimulate release of arachidonic acid
from membrane phospholipids by
PLA2 PC/PE + PLA2: AA
AA + COX (cyclo-oxygenase) : PGG2
(PGH2)
(Platelets)
PGG2 + thromboxane
synthetase TXA2 (thromboxane
A2) TXA2 platelet aggregation
TXA2 TXB2
(Endothelial cells)
PGG2 + PGI2 (prostacyclin synthetase)
PGI2 inhibits platelet aggregation
Platelets
Endothelial cells
The Cyclooxygenase
(Eicosanoid) Pathway in the
Endothelial Cell
TXA2 stimulates platelet
aggregation by decreasing
cAMP
calcium is released
from the DTS
stimulating
platelet aggregation and
secondary hemostasis. PGI2
inhibits platelet aggregation
by increasing cAMP
movement of calcium into DTS
This inhibits platelet activation
Absence of Prostacyclin
cAMP
Thrombin
MOST potent platelet agonist , it activates
and recruits more platelets to the site.
HOW ??
Thrombin is a protease.
Platelet activation by thrombin is mediated
via Thrombin Receptors (on platelet surface)
called PARs (protease-activated receptors) :
PAR-1 and PAR-4
After Recruitment,
Divalent fibrinogen or multivalent vWF
molecules bridge adjacent platelets
together to form platelet aggregates.
Platelet Function
Testing
PFA-100 System
Clinical Indications
Built-In Printer
LCD screen
Soft keys
Trigger solution container
Test Cartridge
Cassette
Carousel
before
after
p = -40 mBar
cup
aperture
150 M
800 l
blood
Filter
+
epinephrine
or ADP
collagen
capillary
200 M
flash
membrane
Platelet
plug
PFA-100
high
high shear
shear rate
rate
>5000
/s
>5000 /s
endothelial cell
collagen fibrils
Epinephrine
or
ADP
membrane with
collagen coating
von Willebrand Factor
von Willebrand
Factor
fibrinogen
erythrocyte
platelet
platelet
FLOW
erythrocyte
lumen
capillary 200m
Expected Values
Col/Epi Col/ADP
3.8% (129mM) buffered Sodium citrate;
90% Central Interval (sec)**:
85 - 165 71 - 118
Petechiae 1-3mm
Purpura 3mm-10 mm
Ecchymosis >10mm