TRANS PPT TOPIC - Platelet

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PLATELET STRUCTURE AND MEGAKARYOPOEISIS HEMATOLOGY II

Luyaben, Pilit, Baligod, Cabucana, Dangelan Topic# 3

TRANS PPT TOPIC 5: PLATELET STRUCTURE AND MEGAKARYOPOEISIS

TOPIC OUTLINE
I. Overview of Platelet
II. Platelet Structure
III. Platelet Ultarstructure
i. Peripheral zone
ii.Submembrane area
iii. Soft Gel zone
IV. Platelet Membrane System
V. SUMMARY

OVERVIEW PLATELET
 Also known as Thrombocytes
 Fragmentation of Metamegakaryocytes PLATELET LIFE SPAN AND TURN OVER RATE
 70-80%( 2/3) circulate in the blood
Fig 1. Platelet Reference Range 150-400 x 109/L
 20-30% (1/3) of platelets pool in the spleen
o Splenectomy: High platelet count  Under healthy state condition, the rate of platelet release
from metamegakaryocytes is equivalent to the rate of
o Splenomegaly: Low platelet count
platelet removal from the circulation.
 Newly released platelets are larger more active
 Platelet turn-over or the net rate of production is
metabolically and hemostatically effective.
estimated to be 35 x 109/L (+/- 4.3) per day
ORIGIN OF THE WORD “PLATELET”  Life span: 7 to 10 day

1881 Bizzozero used in an Italian paper the name PLATELET STRUCTURE


“piastrini (coin)”
1882 in a German literature, he used the term
“Blutplattchen” which means “platte” or plate
1901 Dekhuyzen used the term “thrombocyten”
1910 James Wright gave the name of “blood
plate”, later changed this to “platelet”

HISTORY OF CLINICAL RECOGNITION & INVESTIGATION

1842 Platelets were first described


1878 Platelets were recognized as elements of
the blood
Early Qualitative platelet evaluation using
1900 bleeding time by Duke
1940 Platelet structure was studied using
electron microscope
Early Quantitation of platelets using Fig 2. Platelet Structure
part of hemocytometer, microscope and stain
the specific for platelet  2 – 4 µm
20th  Discoid or round-oval, non-nucleated
centur  Romanowsky stain (light microscopy): blue-purple or lilac
y  Platelets contain fine purple granule (granulomere in
1950 Platelet count using phase -contrast center) and pale cytoplasm (hyalomere)
microscopy  On the average, if platelet count is normal at least 1
At Platelets are enumerated by automated platelet in 10 to 30 RBC found or 8 to 20 platelets per OIO
presen analyzers o Large platelets are seen in ITP, Bernard Soulier
t
PLATELET ULTRASTRUCTURE
 It has three main zones: (thru electron microscopy)
1. Peripheral zone
o Submembrane Area

HEMA II INTRO TO CLINICAL CHEM (LEC#1) Page 1 of 4


PLATELET STRUCTURE AND MEGAKARYOPOEISIS HEMATOLOGY II
Luyaben, Pilit, Baligod, Cabucana, Dangelan Topic# 3

2. Sol-gel zone
3. Organelle zone
Fig. 5 Plasma Membrane
 Membrane system
 PLATELET MEMBRANE RECEPTORS:
o Surface-connected canalicular system (SCCS)
o Cell Adhesion Molecule (CAM)
o Dense tubular System (DTS)
- Integrin family
PLATELET ULTRASTRUCTURE: PERIPHERAL ZONE - Leucine-rich family
 Receptor sites for thrombogenic agents - Selectin family
 Consist of: - Quadraspanin family
o Glycocalyx
PLATELET MEMBRANE RECEPTORS
o Plasma membrane
- Immunoglobulin family
- Submembrane Area
o Seven Transmembrane Receptors (STR)

CELL ADHESION MOLECULE (CAM)


INTEGRIN FAMILY  Integral to membrane
 Ca++ dependent GPIIb/IIIa
most abundant, Cell-cell or
cell-substrate interaction
 Receptor to Fibrinogen,
vWF, fibronectin
LEUCINE-RICH  Adhesion to subendothelial
GLYCOPROTEIN collagen (COL) mediated by
FAMILY vWF by transmembrane
complex GPIb/IX.
 It stabilizes PLT membrane
by interaction with
Fig. 3 Peripheral zone
cytoskeleton
 GLYCOCALYX
o the amorphous exterior coat. QUADRASPANIN  Plasma membrane protein
FAMILY p24/CD9 interacts with
o It is negatively charged.
GPIIb/IIIa, modulating
o It is the site of platelet functional environment (platelet
adhesion molecules.
antigenicity and adhesion receptors)
 It leads to Ca++ increase
and subsequent PLT
activation and aggregation.

IMMUNOGLOBULIN  Functional role unclear but


SUPERGENE has a role in cellular
FAMILY interactions
 includes the ICAMs
(CD50,CD54,CD102)

SEVEN TRANSMEMBRANE RECEPTORS (STR)


 They have seven hydrophobic anchoring domains
Fig. 4 Glycocalyx
supporting an external binding site and an internal
 PLASMA MEMBRANE
terminus that interacts with G protein for outside-in
o serves as the physical and chemical barrier between
platelet signaling
the intracellular and extracellular constituents of
ADDITIONAL PLATELET MEMBRANE RECEPTOR
platelets
 PECAM ( CD31)
 FcγIIA (CD32)
 P-selectin (CD62)

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PLATELET STRUCTURE AND MEGAKARYOPOEISIS HEMATOLOGY II
Luyaben, Pilit, Baligod, Cabucana, Dangelan Topic# 3

PLATELET ULTRASTRUCTURE: ORGANELLE ZONE

 It serves as the metabolic center to influence platelet


function in response to exogenous stimuli such as
hypercoagulation, viruses and foreign bodies.
 It consists of granules:
o Alpha
o Dense bodies
o Lysosome
o Mitochondria

PLATELET MEMBRANE RECEPTORS ( ALPHA GRANULES)


 ALPHA (a) GRANULES
o They have a diameter of 300- 500nm.
o There are 50 to 80 α-granules in each platelet
o They participate in platelet adhesion and aggregation
and support plasma coagulation.

ALPHA (a) GRANULE FUNCTIONS


Fig, 6 Peripheral zone: Receptors Β-Thromboglobulin  Inhibit heparin; vessel repair
PLATELET ULTRASTRUCTURE: SUBMEMBRANE AREA PF4  Inhibit heparin
 Underlies the plasma membrane PDGF (platelet  Vessel repair; smooth muscle
 Separates the organelles from the peripheral zone derived growth cell growth
 Contains filamentous system which helps maintain the factor)
shape of the platelet Fibrinogen  Fibrin formation
 Contains the phospholipid membrane (PF3) Factors V & VIII
vWF  Platelet adhesion
PLATELET ULTRASTRUCTURE: SOFT-GEL ZONE
Plasminogen  Precursor of plasmin
 Cytoskeletal or contractile region
(fibrinolysis)
 Responsible for the discoid shape of platelets until it is 1-antiplasmin  Plasmin inhibitor
stimulated
HMWK  Contact activation: intrinsic
 Consist of:
coagulation path
o Microtubules (Tubulin): for the cytoskeletal support
of the platelet Fibronectin  Promotes PLT spreading
o Microfilaments (Actin/Myosin): platelet contraction &
pseudopod formation
- Thrombasthenin (actomyosin)– main contractile  DENSE GRANULES
protein of platelet (15%); needed for clot retraction o Also called dense bodies
o they are 250-350nm in diameter
o MEMBRANE
PLATELET There are 2 to 7 dense granules
RECEPTORS (DENSE per platelet
GRANULES)
o They migrate to the plasma membrane and release
their content directly into the plasma membrane and
release their contents directly into the plasma upon
platelet activation

DENSE GRANULES FUNCTIONS


ADP/ATP Promotes primary platelet
aggregation
Calcium Regulates platelet
activation
Serotonin (5-HT) Promotes vasoconstriction
Lysosomes (Proteolytic, Digest vessel wall matrix
hydrolytic enzymes) and debris
Contributes to cell lysis
Fig. 7 Structural zone ( Submembrane and Softgel zone)
Mitochondria ATP synthesis for PLT

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PLATELET STRUCTURE AND MEGAKARYOPOEISIS HEMATOLOGY II
Luyaben, Pilit, Baligod, Cabucana, Dangelan Topic# 3

metabolism

PLATELET MEMBRANE SYSTEM


 SURFACE CONNECTING CANALICULAR SYSTEM
o Tubular invagination of membrane.
o It serves as the delivery route for substances ingested
or extruded by the platelets. (communication)
 DENSE TUBULAR SYSTEM
o It is an Endoplasmic reticulum remnant.
o It contains specific peroxidase activity important for
platelet prostaglandin and Thromboxane synthesis
(TXa2).
o It is the site of arachidonic acid metabolism & calcium
sequestering pump.
o It is also the site for Calcium storage/release.

SUMMARY:
- Platelets are derived from BM megakaryocytes.
- Circulating platelets are anucleate, but have a
distinctive anatomy and physiology that enables them
to play important roles in primary and secondary
hemostasis.
- The PLT membrane houses numerous receptors that
control PLT activation.
- PLTs adhere to surfaces, aggregate with each other,
and secrete their granules’ contents in order to plug
damaged areas in endothelia, modulate coagulation,
and aid tissue repair

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