Platelet Structure and Function in Physiology
Platelet Structure & Function
DR.MOHAMMED ALOTAIBI
MRes, PhD (Liverpool, England)
Assist. Professor of Physiology,
College of Medicine
King Khalid University Hospital
King Saud University
At the end of this lecture the student
is expected to:
-
Understand platelet
normal ultrastructure
-
Understand the functions of different platelets
organelles and surface receptors
-
Understand the mechanisms of platelet functions
-
Relate membrane receptors and granule content to
normal function in hemostasis and bleeding
(platelet) disorders
BLOOD
BLOOD
Plasma
Plasma
Cells
Cells
R
R
B
B
C
C
W
W
B
B
C
C
P
P
l
l
a
a
t
t
e
e
l
l
e
e
t
t
What are platelets?
B
B
o
o
n
n
e
e
m
m
a
a
r
r
r
r
o
o
w
w
M
M
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k
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y
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p
p
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l
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t
t
s
s
What are platelets?
Platelets –
cont.
•
Site of formation:
Bone marrow
•
Steps:
Stem cell
Megakaryoblast
Megakaryocyte
Platelets
Megakayocyte and platelet formation
Platelets Formation
(Thrombopoiesis)
Regulation of thrombopoiesis
by
Thrombopoietin
Platelet ultra-structure
(Electron-microscope -EM)
P
l
a
t
e
l
e
t
s
(
T
h
r
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m
b
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t
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)
-
D
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c
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~
1
-
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μ
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1
5
0
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0
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n
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3
0
0
,
0
0
0
/
μ
l
•
Anuclear and discoid cell
spherical when
activated
•
Life span:
7–10
days
•
Sequestered in the spleen;
hypersplenism
may lead to low platelet counts.
(Thrombocytes)
α
α
Granules
Granules
von Willebrand Factor
von Willebrand Factor
Fibrinogen
Fibrinogen
Chemokines (PF4,etc.)
Chemokines (PF4,etc.)
Thrombospondin
Thrombospondin
P-selectin
P-selectin
Platelet Ultrastructure
Dense Granules
Dense Granules
ADP/ATP
ADP/ATP
Calcium
Calcium
Serotonin
Serotonin
M
M
i
i
t
t
o
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c
c
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m
m
Platelet Receptors
Platelet
G
P
I
b
-
I
X
-
V
(
(
v
v
W
W
F
F
a
a
c
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r
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)
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G
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)
(
(
GP Ia, GP VI)
GP Ia, GP VI)
C
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a
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e
n
(TP
α
)
T
X
A
2
(
P
2
Y
1
2
)
A
D
P
General functions of
the platelets
H
E
M
O
S
T
A
S
I
S
1.
VASCULAR PHASE
2. PLATELET PHASE
3.
COAGULATION PHASE
4.
FIBRINOLYTIC PHASE
Platelet Activation
•
Adhesion
•
Shape change
•
Aggregation
•
Secretion
(Release reaction)
•
Clot Retraction
Adhesion
Platelet function
(
(
v
v
W
W
F
F
)
)
Activation
Platelet function
R
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s
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S
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Further Spread of
Convolutions to psuedopods
E
a
r
l
y
S
p
r
e
a
d
p
l
a
t
e
l
e
t
Aggregation
Platelet function
•
Aggregation:
Fibrinogen
is needed to join platelets to
each other via platelet fibrinogen
receptors
G
P
I
I
b
/
I
I
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a
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p
t
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s
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)
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p
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t
Platelet Aggregation
von Willebrand factor
(vWF)
and Platelet Adhesion
Secretion
Platelet function
Activated Platelets
Secrete:
1.
5HT
(
serotonin)
vasoconstriction
2.
Platelet phospholipid (PF3)
clot
formation
3.
Thromboxane A
2
(TXA
2
) is a
prostaglandin formed from
arachidonic acid
Function:
–
Vasoconstriction
–
Platelet aggregation
(
TXA
2
inhibited by aspirin)
Myosin
,
actin filaments
and
thrombosthenin
in platelets are
stimulated to
contract during aggregation
further reinforcing the plug
and help release of
granule contents
Clot Retraction
Platelets activated by adhesion
Platelets activated by adhesion
Extend projections to make contact with each
Extend projections to make contact with each
other
other
Release:
Release:
thromboxane A2
thromboxane A2
,
,
serotonin & ADP >>> activating
serotonin & ADP >>> activating
other platelets
other platelets
Serotonin & thromboxane A2 are
Serotonin & thromboxane A2 are
vasoconstrictors
vasoconstrictors
decreasing blood flow through the injured vessel.
decreasing blood flow through the injured vessel.
ADP causes stickiness and enhances aggregation
ADP causes stickiness and enhances aggregation
Platelet haemostatic plug formation
P
l
a
t
e
l
e
t
A
c
t
i
v
a
t
i
o
n
-
s
u
m
m
a
r
y
•
Platelets are activated when brought into contact with
collagen exposed when the endothelial blood vessel lining is
damaged
•
Activated platelets release a number of different coagulation
and platelet activating factors
•
Transport of negatively charged
phospholipids
to the platelet
surface; provide a catalytic surface for coagulation cascade
to occur
•
Platelets adhesion receptors (integrins): Platelets adhere to
each other via adhesion receptors forming a hemostatic plug
with fibrin
•
Myosin and actin filaments in platelets are stimulated to
contract during aggregation further reinforcing the plug and
help release of granule contents
•
GPIIb/IIIa: the most common platelet adhesion receptor for
fibrinogen and von Willebrand factor (vWF)
General functions of the platelets:
•
Platelet plug formation
•
Platelets and blood coagulation
A
d
e
q
u
a
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n
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m
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m
o
s
t
a
s
i
s
Maintenance of vascular integrity
Initial arrest of bleeding by
platelet plug formation
Stabilization of hemostatic plug
by contributing to fibrin formation
B
l
e
e
d
i
n
g
D
i
s
o
r
d
e
r
s
•
B
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d
i
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g
c
a
n
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s
u
l
t
f
r
o
m
:
–
P
l
a
t
e
l
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t
d
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f
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c
t
s
:
D
e
f
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r
(
t
h
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)
D
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f
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(
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)
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B
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d
i
s
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r
d
e
r
s
Platelet function
Congenital Platelet Disorders
Disorders of
Adhesion:
. Bernard-Soulier Syndrome
Disorder of
Aggregation:
.
Glanzmann thrombosthenia
Disorders of
Granules:
.
Grey Platelet Syndrome
. Storage Pool deficiency
. Hermansky-Pudlak syndrome
.
Chediak-Higashi syndrome
Bernard-Soulier Syndrome
P
l
a
t
e
l
e
t
GP Ib-IX-V
GP Ib-IX-V
(vW Factor)
GP IIb-IIIa
(Fibrinogen, vWF)
Collagen
Collagen
(GP Ia, GP VI)
TXA2
TXA2
ADP
ADP
Bernard-Soulier Syndrome
P
l
a
t
e
l
e
t
GP IIb-IIIa
GP IIb-IIIa
(Fibrinogen, vWF)
(Fibrinogen, vWF)
Collagen
Collagen
(GP Ia, GP VI)
(GP Ia, GP VI)
TXA2
TXA2
ADP
ADP
(vW Factor)
(vW Factor)
Glanzmann Thromasthenia
P
l
a
t
e
l
e
t
GP Ib-IX-V
GP Ib-IX-V
(vW Factor)
(vW Factor)
Collagen
Collagen
(GP Ia, GP VI)
(GP Ia, GP VI)
TXA2
TXA2
ADP
ADP
Glanzmann Thromasthenia
P
l
a
t
e
l
e
t
GP Ib-IX-V
(vW Factor)
(vW Factor)
Collagen
(GP Ia, GP VI)
TXA2
ADP
Glanzmann Thrombasthenia
Platelet function tests
How to investigate for
platelet disorders?
Laboratory Testing of Platelet Functions
Platelet count
(& shape)
Bleeding time
Platelet Aggregation
Platelet Function Analyzer
(PFA-100
)
Flow-cytometry
Electron-microscopy
Granule release products
White GC et al. Approach to the Bleeding Patient. In Colman, RW et al. Hemostasis and thrombosis 2
nd
ed. 1987
Bleeding Time
Laboratory Testing of Platelet Functions
Platelet Aggregometer
(in PRP):
Provides information on time course of plat.
activation.
Agonists:
ADP
Adrenaline
Collagen
Arachidonic acid
Ristocetin
Thrombin
Reference ranges
need to be determined for
each agonist (
+
Dose responses)
Whole
Whole
blood
blood
PRP
PRP
RBC
RBC
Agonists:
•
ADP
•
Adrenaline
•
Collagen
•
Arachidonic acid
•
Ristocetin
•
Thrombin
•
Platelet Aggregation
Normal Platelet
Aggregation
S
u
m
m
a
r
y
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Platelets play a crucial role in hemostasis and bleeding disorders. This lecture by Dr. Mohammed Alotaibi covers the ultrastructure of platelets, functions of organelles and surface receptors, mechanisms of platelet functions, and the relationship of membrane receptors and granule content in normal hemostasis. It also delves into platelet formation, regulation by thrombopoietin, and the intricate ultrastructure involving microtubules, granules, Von Willebrand factor, and more.
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Presentation Transcript
Platelet Structure & Function DR.MOHAMMED ALOTAIBI MRes, PhD (Liverpool, England) Assist. Professor of Physiology, College of Medicine King Khalid University Hospital King Saud University
Objectives At the end of this lecture the student is expected to: - Understand plateletnormal ultrastructure - Understand the functions of different platelets organelles and surface receptors - Understand the mechanisms of platelet functions - Relate membrane receptors and granule content to normal function in hemostasis and bleeding (platelet) disorders
What are platelets? BLOOD Plasma Cells RBC WBC Platelet
What are platelets? Mature platelets Bone marrow Megakaryocyte
Platelets cont. Site of formation: Bone marrow Steps: Stem cell Megakaryoblast Megakaryocyte Platelets
Platelets Formation (Thrombopoiesis) Regulation of thrombopoiesis by Thrombopoietin
Platelet ultra-structure (Electron-microscope -EM)
Platelets (Thrombocytes) - Discs ~ 1-4 M in diameter - Their normal concentration in the blood is between 150,000 and 300,000 / l
(Thrombocytes) Anuclear and discoid cell activated Life span: 7 10 days Sequestered in the spleen; hypersplenism may lead to low platelet counts. spherical when
Platelet Ultrastructure Microtubules Mitochondria Granules von Willebrand Factor Fibrinogen Chemokines (PF4,etc.) Thrombospondin P-selectin Open canalicular system Dense Granules ADP/ATP Calcium Serotonin
Platelet Receptors Platelet (GP Ia, GP VI) Collagen GP Ib-IX-V (vW Factor) (TP ) TXA2 GP IIb-IIIa (Fibrinogen, vWF) (P2Y12) ADP
General functions of the platelets
HEMOSTASIS 1. VASCULAR PHASE 2. PLATELET PHASE 3. COAGULATION PHASE 4. FIBRINOLYTIC PHASE
Platelet Activation Adhesion Shape change Aggregation Secretion (Release reaction) Clot Retraction
Platelet function Adhesion GP Ib-IX-V (vW Factor) (GP Ia, GP VI) Collagen (vWF) Platelet GP IIb-IIIa (Fibrinogen, vWF)
Platelet function Activation
Resting platelet Activated platelet
Convolutions Spread to psuedopods Smooth surface psuedopods Convolutions In body Early Further Spread of Convolutions to psuedopods Spread platelet
Platelet function (GP Ia, GP VI) Collagen GP Ib-IX-V (vW Factor) Platelet (TP ) TXA2 GP IIb-IIIa (Fibrinogen, vWF) Aggregation (P2Y12) ADP Aggregation: Fibrinogen is needed to join platelets to each other via platelet fibrinogen receptors
Platelet Aggregation Activated platelet Resting platelet Fibrinogen Agonist GP IIb/IIIa receptors (unreceptive state) Aggregating platelets
von Willebrand factor (vWF) and Platelet Adhesion Blood Flow Fibrinogen vWF Platelet A1 domains GPIb- IX-V Plug Recruitment Adhesion Rolling Activation Formation
Platelet function Secretion
Activated Platelets Secrete: 1. 5HT (serotonin) 2. Platelet phospholipid (PF3) formation 3. Thromboxane A2 (TXA2) is a prostaglandin formed from arachidonic acid Function: Vasoconstriction Platelet aggregation (TXA2 inhibited by aspirin) vasoconstriction clot
Clot Retraction Myosin, actin filaments and thrombosthenin in platelets are stimulated to contract during aggregation further reinforcing the plug and help release of granule contents
Platelet haemostatic plug formation Platelets activated by adhesion Extend projections to make contact with each other Release: thromboxane A2, serotonin & ADP >>> activating other platelets Serotonin & thromboxane A2 are vasoconstrictors decreasing blood flow through the injured vessel. ADP causes stickiness and enhances aggregation
Platelet Activation- summary Platelets are activated when brought into contact with collagen exposed when the endothelial blood vessel lining is damaged Activated platelets release a number of different coagulation and platelet activating factors Transport of negatively charged phospholipids to the platelet surface; provide a catalytic surface for coagulation cascade to occur Platelets adhesion receptors (integrins): Platelets adhere to each other via adhesion receptors forming a hemostatic plug with fibrin Myosin and actin filaments in platelets are stimulated to contract during aggregation further reinforcing the plug and help release of granule contents GPIIb/IIIa: the most common platelet adhesion receptor for fibrinogen and von Willebrand factor (vWF)
General functions of the platelets: Platelet plug formation Platelets and blood coagulation
Maintenance of vascular integrity Adequate number and function of platelet is essential to participate optimally in hemostasis Stabilization of hemostatic plug by contributing to fibrin formation Initial arrest of bleeding by platelet plug formation
Bleeding Disorders Bleeding can result from: Platelet defects: Deficiency in number (thrombocytopenia) Defeciency in function (acquired or congenital)
Platelet function Bleeding disorders abnormal number or function of platelet
Congenital Platelet Disorders Disorders of Adhesion: . Bernard-Soulier Syndrome Disorder of Aggregation: . Glanzmann thrombosthenia Disorders of Granules: . Grey Platelet Syndrome . Storage Pool deficiency . Hermansky-Pudlak syndrome .Chediak-Higashi syndrome
Bernard-Soulier Syndrome Platelet GP Ib-IX-V Collagen (GP Ia, GP VI) (vW Factor) TXA2 GP IIb-IIIa (Fibrinogen, vWF) ADP
Bernard-Soulier Syndrome Platelet Collagen (GP Ia, GP VI) (vW Factor) TXA2 GP IIb-IIIa (Fibrinogen, vWF) ADP
Glanzmann Thromasthenia Platelet GP Ib-IX-V Collagen (GP Ia, GP VI) (vW Factor) TXA2 GP IIb-IIIa (Fibrinogen, vWF) ADP
Glanzmann Thromasthenia Platelet GP Ib-IX-V (vW Factor) Collagen (GP Ia, GP VI) TXA2 ADP
Glanzmann Thrombasthenia Fibrinogen IIb-IIIa Normal No Gp IIb-IIIa Receptors
How to investigate for platelet disorders? Platelet function tests
Laboratory Testing of Platelet Functions Platelet count (& shape) Bleeding time Platelet Aggregation Platelet Function Analyzer (PFA-100) Flow-cytometry Electron-microscopy Granule release products White GC et al. Approach to the Bleeding Patient. In Colman, RW et al. Hemostasis and thrombosis 2nd ed. 1987
Bleeding Time Bleeding time 1 Bleeding time 2 Bleeding time 3
Laboratory Testing of Platelet Functions Platelet Aggregometer (in PRP): Provides information on time course of plat. activation. Agonists: ADP Adrenaline Collagen Arachidonic acid Ristocetin Thrombin Reference ranges need to be determined for each agonist (+ Dose responses)
Platelet Aggregation Agonists: ADP Adrenaline Collagen Arachidonic acid Ristocetin Thrombin Whole blood RBC PRP
Summary Platelets are cell fragments derived from megakaryocyte in the bone marrow Platelets play a pivotal role in hemostasis by arresting bleeding from injured blood Vessels Bleeding can result from: Platelet defects acquired or congenital
