Platelet Activation

Platelets (Thrombocytes)
• 2- 4 micromillimeters in diameter
• 250,000 – 400,000 per microliter (too few
thrombocytopenia – too many
• Lifespan on average 6 – 10 days
• 1/3 trapped in spleen (for reserve)
• No significant marrow reserve
• 5 –days for new production
Genesis of Platelets
Platelets are fragments of Megakaryocytes
Each megakaryocyte can produce 2,000 – 5,000 platelets
They are primarily produced under the influence of
Thrombopoietin – a hormone produced in the kidney and
liver along with IL 3, 6 and 11.
Stem cell
Developmental pathway
Figure 17.12
• Platelets are non-nucleated fragments of
megakaryocytes with a blue-staining outer region
(Hyalomere and a purple granular center (Granulomere)
• The Hyalomere is where the surface opening tubular
system is found and the Dense Tubular system
• Open tubular system is site for rapid release and uptake
of chemicals associated with granules (stained vesicles)
• Dense tubular system sequesters calcium so as to
prevent platelet stickiness
• Their granules are termed alpha, beta and
lambda contain serotonin, Ca2+, enzymes, ADP,
and platelet-derived growth factor (PDGF)
• Platelets function in the clotting mechanism
by forming a temporary plug that helps seal
breaks in blood vessels
• Platelets not involved in clotting are kept
inactive by NO and prostacyclin
Granulomere (region that contains
• Alpha Granules contain Fibrinogen, Platelet
Derived Growth Factor, Thrombospondin and
certain coagulation factors (Von Willebrand
Factor) and Factor V
• Dense Granules contain Calcium, ADP, ATP,
serotonin, histamine, pyrophosphatase
• Lambda Granules are lysosomes
Platelet’s other organelles
• Mitochondria
• Cytoskeleton – microtubules and other
proteins for example Actin and Myosin
Platelet Activation (Formation of Platelet Plug)
Injured blood vessels release Von Willebrand Factor and
Tissue Factor and exposure of Collagen
1. Shape Change (Cytoskeleton)
2. Platelet Aggregation –(surface ADP and
3. Degranulation
Platelet Plug Formation
1. Normally the intact endothelium produces
prostacyclin and Nitric Oxide, which inhibit
platelet aggregation. It also blocks coagulation
by the presence of thrombomodulin and
heparin-like molecule on its surface membrane.
These two membrane-associated molecules
inactivate specific coagulation factors.
2. Injured endothelial cells release Von Willebrand
factor and tissue thromboplastin and cease the
production and expression of inhibitors of
coagulation and platelet aggregation. They also
release endothelin, a powerful vasoconstrictor.
3. Platelets (1) avidly adhere to subendothelial
collage especially in the presence of Von
Willebrand factor, (2) release the contents of
their granules, and (3) adhere to one another.
These three events collectively are termed
platelet activation.
4. The release of some of their granular contents
especially *adenosine diphosphate (ADP), and
thrombospondin, makes platelets “sticky”
causing circulating platelets to adhere to
collagen-bound platelets and to degranulate.
* Note Plavix Action-
5. Arachidonic acid formed in the platelet
membrane is converted to thromboxane A2,
and potent vasoconstrictor and platelet
6. The aggregated platelets act as a plug,
blocking bleeding. In addition they express
platelet factor 3 on their cell membrane,
providing the necessary phospholipid surface
for the proper assembly of the coagulation
factors (especially thrombin).
7. As part of the complex cascade of reactions
involving the various coagulation factors, tissue
thromboplastin and platelet thromboplastin
both act on circulating prothrombin, converting
it into thrombin. Thrombin is an enzyme that
facilitates platelet aggregation. In the presence
of calcium (Ca+2), it also converts fibrinogen to
8. The fibrin monomers thus produced polymerize
and form a reticulum of a clot, entangling
additional platelets, RBCs and WBCs in a stable,
gelatinous blood clot (thrombus). The RBCs
facilitate platelet activation, whereas
neutrophils, and endothelial cells limit both
platelet activation and thrombus size.
9. Approximately 1 hour after clot formation,
actin and myosin monomers form thick and
thin filaments, which interact by utilizing ATP
as their energy source. As a result the clot
retracts to about ½ its previous size, pulling
the edges of the vessel closer together, and
minimizing blood loss.
10.When the vessel is repaired, the endothelial
cells release plasminogen activators, which
convert plasminogen to plasmin, the enzyme
that initiates lysis of the thrombus. The
lysosome enzymes in the platelets assist in
this action.
• Plavix (clopidogrel bisulfate) is an inhibitor of
ADP-induced platelet aggregation acting by direct
inhibition of adenosine diphosphate (ADP)
binding to its receptor and of the subsequent
ADP-mediated activation of the glycoprotein
GPIIb/IIIa complex. Chemically it is methyl (+)-(S)α(2-chlorophenyl)-6,7-dihydrothieno[3,2c]pyridine-5(4H)-acetate sulfate (1:1). The
empirical formula of clopidogrel bisulfate is
C16H16ClNO2S•H2SO4 and its molecular weight is
• Aspirin also has an antiplatelet effect by by
blocking COX 1 – thus inhibiting the
production of thromboxane, which under
normal circumstances binds platelet
molecules together to create a patch over
damage of the walls within blood vessels.
• Pseudothrombocytopenia – in vitro due to
antibodies created in test tube due to the use
of EDTA.
• Infection induced – many viral and bacterial
infections cause this in particular HIV
• Drug induced – several drugs cause
thrombocytopenia especially heparin therapy
• Immune (Idiopathic)Thrombocytopenia
• Thrombotic Thrombocytopenia
Idiopathic Thrombocytopenia Purpura
a condition of having a low platelet count
(thrombocytopenia) of no known cause
(idiopathic). As most causes appear to be related
to antibodies against platelets, ITP is also known as
immune thrombocytopenic purpura or immunemediated thrombocytopenic purpura.
ITP Signs and symptoms
Signs include the development of bruises (purpura) and
petechiae, especially on the extremities, bleeding from
the nostrils and bleeding at the gums, any of which may
occur if the platelet count is below 20,000 per mm3.
A very low count (<10,000 per mm3) may result in the
formation of hematomas in the mouth or on other
mucous membranes.
Serious and possibly fatal complications due to an
extremely low count (<5,000 per mm3) may include
subarachnoid or intracerebral hemorrhage, lower
gastrointestinal bleeding or other internal bleeding.
Thrombotic Thrombocytopenia
Purpura (TTP)
a rare disorder of the blood-coagulation system, causing
extensive microscopic thromboses to form in small blood
vessels throughout the body (thrombotic microangiopathy).
Most cases of TTP arise from inhibition of the enzyme
ADAMTS13, a metalloprotease responsible for cleaving large
multimers of von Willebrand factor (vWF) into smaller units. A
rarer form of TTP, called Upshaw-Schülman syndrome, is
genetically inherited as a dysfunction of ADAMTS13. If large
vWF multimers persist there is tendency for increased
Thrombocytosis is almost always due to (1) iron
deficiency (2) inflammation, cancer or
Infection (reactive thrombocytosis); or (3) an
underlying myeloproliferative disorder.

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