Platelet function
Platelets
Small anucleate cells
Play a critical role in hemostasis and thrombosis
Normal range in human is 150 – 400 × 10 9 /L
The normal life span of a platelet is 10 days
Platelet production
Platelets are produced in the bone marrow by
fragmentation of the cytoplasm of megakaryocytes
Mature megakaryocytes are extremely large with an
eccentrically placed single lobulated nucleus
The precursor for megakaryocytes is
megakaryoblast
The nucleus of the megakaryocyte undergoes a
process known as endomitosis that involves nuclear
replication without cellular division
This enlarge cytoplasmic volume
Platelets are formed by the fragmentation from the
tips of cytoplasmic extensions of megakaryocyte
cytoplasm
Each megakaryocyte giving rise approximately to
1000 – 5000 platelets
The time interval from differentiation of human
stem cell to the production of platelets average 10
days
Thrombopoietin is the major regulator of platelet
formation
95% of thrombopoietin is produced by the liver
As platelets age, they lose surface sialic acid, this
signals production of new thrombopoietin
Platelet structure
Extremely small and discoid in shape
Approximately 3.0 × 0.5 μm in diameter
Mean volume of platelet is 7 – 11 Fl
The discoid shape and small size enables platelets to be
marginated by the red blood cells to the edge of the
vessel
This disc shape is not essential for platelet function
Contain four main types of storage granules
- Dense granules
- α granules
- Lysosomes
- Peroxisomes
Dense granules
5 -9 dense granules in a platelet
Contain high levels of ADP, ATP, seratonin and Ca2+
Lysosomes
Contain hydrolytic enzymes
α granules
About 80 granules per platelet
Contain a rich diversity of proteins and membrane
receptors that support haemostasis, vascular
repair, inflammation and host defense (clotting
factors, VWF, platelet derived growth factor)
Platelet antigens
Several platelet surface proteins have been found to
be important antigen in platelet specific
autoimmunity
Platelets also express ABO and human leukocyte
antigen (HLA) class I
Platelet function
The main function of platelets is the formation of
mechanical plugs during the normal hemostatic
response to vascular injury
3 major functions
- Platelet adhesion
- Platelet aggregation
- Release reaction and amplification
Damage to the vasculature
VWF bind to collagen
Conformational changes of VWF
Interaction of VWF with the GPIb-IX-V complex
Platelet adhesion
Following blood vessel injury, platelets adhere to the
exposed subendothelial matrix proteins via special
adhesive glycoproteins (GPIa and GPIb receptors).
Under conditions of high shear, (e.g. arterioles), the
exposed subendothelial matrix is initially coated with
VWF.
The platelets then make contact with VWF via the GPIb-
XI-V complex on platelets.
This initiates platelet rolling in the direction of blood
flow over the exposed VWF with activation of GPIIb/IlIa
receptor
Firm adhesion is established
Under low shear conditions, platelets adhere
predominantly to collagen of the subendothelium.
Collagen bind initially to GPIa/IIa, cross-links many of
these and it activates platelets
This ligand receptor binding results in a complete
cascade of signals which results in platelet activation.
The events that follow are shape change and
spreading, activation of GPIIb/IlIa and granule
secretion.
Platelets become more spherical and extrude
pseudopodia which enhance platelet-platelet
interaction.
The end result of spreading is a flattened spread out
platelet with granules and organelles in the center,
resulting in a characteristic fried egg appearance.
These changes are brought about by the actin
cytoskeleton.
The granules are secreted from the center of the cell.
Platelet aggregation
It is characterized by cross-linking of platelets
through active GPIIb/IIIa receptors with fibrinogen
bridges.
A resting platelet has GPIIb/IlIa receptors, which do
not bind fibrinogen, VWF or other ligands.
Stimulation of a platelet leads to an increase in
GPIIb/Illa molecules, enabling platelet cross-linking
via VWF and fibrinogen bridges
Platelet release reaction and amplification
Primary activation by various agonists induces
intracellular signaling, leading to the release of α
granular content.
α-Granule contents play an important role in platelet
aggregate formation and stabilization.
ADP released from dense granules plays a major positive
feedback role in promoting platelet activation.
Thromboxane A2 is important in secondary amplification
of platelet activation to firm a stable platelet aggregate.
Thromboxane A2 has powerful vasoconstrictive activity.
The release reaction is inhibited by substances like
prostacyclin (PGI2)
Platelet procoagulant activity
After platelet aggregation and release, the exposed
membrane phospholipid (platelet factor 3) is
available for two reactions in the coagulation
cascade
The first (tenase) involves factors IXa, VIlla and X in
the formation of factor Xa
The second (prothrombinase) results in the
formation of thrombin from the interaction of
factors Xa, Va and prothrombin (II)
Natural inhibitors of platelet
function
Nitric oxide (NO) is released from endothelial cells,
macrophages and platelets inhibits platelet
activation and promotes vasodilatation.
Prostacyclin synthesized by endothelial cells also
inhibits platelet function.
Platelet based bleeding problems
Abnormalities in either platelet function and/or
number
Present with a typical mucocutaneous bleeding
pattern
Often prone to bleeding during surgery and
trauma
Congenital defects
- Glanzmann’s thrombasthenia
- Bernard-Soulier syndrome
- Gray platelet disease
Acquired defects
- Commonly due to antiplatelet drugs : Aspirin
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