Platelets

• Aka “thrombocytes” -“cytes” refer to cell;

thrombosis refers blood clotting
• produced from large BM cells called
megakaryocytes, which into the minute platelets
either in BM or soon after entering the blood, esp
as they squeeze through capillaries
• hematocytoblast --> megakaryocyte --> platelets
• The hormone controlling megakaryocyte
development is thrombopoietin
• actually not true cells but merely circulating
fragments of cells
 Though cell fragments:
• Contain many structures critical to stop bleeding.
• Also, a natural source of growth factors
• Releases multitude of growth factors like platelet-
derived growth factor (PDGF), and TGF beta,
which stimulates deposition of extracellular
matrix, - play significant role in repair &
regeneration of connective tissues.
• Other healing-associated growth factors include
basic fibroblast growth factor, insulin-like growth
factor 1, platelet-derived epidermal growth
factor and vascular endothelial growth factor
 Importance of the Platelet
Mechanism for Closing Vascular Holes
• extremely important for closing minute ruptures in
very small blood vessels that occur many thousands
of times daily.
• Indeed, multiple small holes through the endothelial
cells themselves are often closed by platelets actually
fusing with the endothelial cells to form additional
endothelial cell membrane.
• A person who has few blood platelets develops each
day literally thousands of small hemorrhagic areas
under the skin and throughout the internal tissues,
but this does not occur in the normal person.
Physical &Chemical Characteristics
• Minute discs 1 to 4 micrometers in diameter.
• 150,000-350,000 per microliter of blood
• functional characteristics of whole cells, but
no nuclei and cannot reproduce
• a half-life in the blood of 8 to 12 days, so that
over several weeks its functional processes
run out.
• Eliminated mainly by the tissue macrophage
system.
• More than 50% by macrophages in the spleen.
 Cell membrane
• surface has a coat of glycoproteins that
repulses adherence to normal endothelium
but causes adherence to injured areas of
the vessel wall, especially injured
endothelial cells & even more any exposed
collagen from deep within the vessel wall.
• large amounts of phospholipids that
activate multiple stages in the blood-
clotting process,
 Cytoplasm
(1) actin & myosin mols, ie contractile proteins and another
contractile protein, thrombosthenin,
(2) residuals of endoplasmic reticulum & Golgi apparatus that
synthesize various enzymes & store large quantities of ca+
(3) mitochondria and enzyme systems that are capable of
forming (ATP) and ADP)
(4) enzyme systems that synthesize prostaglandins, responsible
for many vascular and other local tissue reactions
(5) an important protein called fibrin-stabilizing factor
discussed later in relation to blood coagulation
(6) a growth factor that causes vascular endothelial cells,
vascular smooth muscle cells, and fibroblasts to multiply and
grow thus helps repair damaged vascular walls.
 Function
Help in hemostasis
i. Hemostasis stages
1. vascular spasm
2. platelet plug formation
a. collagen exposure
b. platelets adhesion
c. ADP release; thromboxane release
* aspirin inhibits this stage
d. platelet accumulation = plug
ii. Clot formation and retraction
a. clot definition
b. Following clot formation the actinomyosin in platelets contracts,
compacting clot & pulling the vessel edges (facilitating repair)
c. Squeezes serum (plasma minus clotting factors) from the clot.
 Platelet Plug
a. activated when the tearing of blood vessel wall exposes
the collagen that underlies the vessel’s endothelium
b. Activated platelets then aggregate at injury site.
c. Aggregated, activated platelets release chemicals that:
enhance vascular spasm; are involved in coagulation; and
facilitate the activation and aggregation of more platelets
at the injury site (a +feedback process).
d. Aggregation of platelets is a platelet plug which is a
temporary seal to the break in the vessel wall.
e. Platelet plug is restricted to the injury site b/c intact
endothelial cells release the chemical prostacyclin, which
inhibits platelet aggregation
 Mechanism of the Platelet Function
• Adhere, activate(+release reaction) and aggregate
• contact with damaged vascular surface (eg collagen fibers in vascular wall) platelets
immediately change their own characteristics drastically.
• Swell; assume irregular forms with numerous irradiating pseudopods
• contractile proteins contract forcefully -release of granules that contain multiple
active factors;
• become sticky, adhere to collagen in the tissues and to a protein called von
Willebrand factor that leaks into the traumatized tissue from the plasma;
• secrete large quantities of ADP; and their enzymes form thromboxane A2
• The ADP and thromboxane act on nearby platelets ,activates them & stickiness of
these additional platelets causes them to adhere to the original activated platelets.
• Thus damaged vascular wall activates successively increasing nos attract more and
more additional platelets, forming a platelet plug- successful in blocking blood loss
if the vascular opening is small.
• Then, during the subsequent process of blood coagulation, fibrin threads form,
attach tightly to the platelets, thus constructing an unyielding plug.
 Thrombus formation
• Platelets function achieved primarily by formation of thrombi, on
damage to the endothelium of blood vessels.
• But thrombus formation must be inhibited if there is no damage
• Inner surface of blood vessels lined with a thin layer of endothelial
cells that inhibits platelet activation by producing nitric oxide,
endothelial-ADPase- clears away the platelet activator, ADP
• Endothelial cells produce a protein called von Willebrand factor
(vWF), which helps endothelial cells adhere to collagen in the
basement membrane
• Under physiological conditions, collagen is not exposed to the
bloodstream. vWF is secreted constitutively into the plasma by the
endothelial cells, and is stored in granules within the endothelial
cell and in platelets.
 Activation
• When endothelial layer is injured, collagen, vWF and
tissue factor from the subendothelium is exposed to the
bloodstream.
• When the platelets contact collagen or vWF, they are
activated (e.g. to clump together). They are also activated
by thrombin (formed with the help of tissue factor).
• They can also be activated by a negatively charged
surface, such as glass. Non-physiological flow conditions
caused by arterial stenosis or artificial devices (Mechanical
Heart Valves, blood pumps etc) can also lead to platelet
activation
• Ca+ essential for binding of these coagulation factors
• Activated platelets change shape,become more spherical
and pseudopods form on their surface.
 Granule secretion
There are three types of granules:
1. Dense (or delta) granules: ADP or ATP, calcium,
and serotonin
2. lambda granules – similar to lysosomes and
contain several hydrolytic enzymes
3. Alpha granules: P-selectin, platelet factor 4,
transforming growth factor-β1, platelet-derived
growth factor, fibronectin, B-thromboglobulin,
vWF, fibrinogen, and coagulation factors V and
XIII.
 Adhesion and aggregation
• Platelets aggregate (clump together) using fibrinogen
& vWF as a connecting agent.
• Most abundant platelet aggregation is a calcium-
dependent receptor for fibrinogen, vitronectin,
thrombospondin & vWF.
• Aggregation and adhesion act together to form the
platelet plug. Myosin & actin filaments in platelets
are stimulated to contract during aggregation,
further reinforcing the plug.
• Platelet aggregation is stimulated by ADP,
thromboxane
 Thromboxane A2 synthesis
• Platelet activation initiates the arachidonic acid
pathway to produce TXA2.
• TXA2 is involved in activating other platelets and
its formation is inhibited by COX inhibitors, such
as aspirin, Ibuprofen.
• Wound repair- aggregated platelets secrete
chemicals that promote invasion of fibroblasts
from surrounding connective tissue into wounded
area to completely heal the wound or form a scar.
The obstructing clot is slowly dissolved by the
fibrinolytic enzyme, plasmin, and the platelets are
cleared by phagocytosis.
 Disorders of Platelets
• An abnormality or disease of the platelets is called a
thrombocytopathy, which could be either a low
number of platelets (thrombocytopenia), a decrease
in function of platelets (thrombasthenia), or an
increase in the number of platelets (thrombocytosis)
• There are disorders that reduce the number of
platelets, such as heparin-induced thrombocytopenia
(HIT) or thrombotic thrombocytopenic purpura (TTP)
that typically cause thromboses, or clots, instead of
bleeding.
 Thrombocytosis
• Rare conditions result in the bone marrow
producing too many platelets, sometimes as
many as one million or two million per
microliter.
• In some of these patients, there are increased
risks for blood clots, but many patients with
these disorders have no problems.
• Causes include Polycythemia vera, Malignancy
 Thrombocytopenia
• Tendency to bleed, as hemophiliacs, but from small venules or
capillaries, rather than from larger vessels as in hemophilia.
• Small punctate hemorrhages throughout all the body tissues ,
Skin displays many small, purplish blotches, giving the disease the
name thrombocytopenic purpura.
• Ordinarily, bleeding will not occur until the levels falls below
50,000/l,
• fails to retract, because normally dependent on release of
multiple coagulation factors from the large nos of platelets
entrapped in the fibrin mesh of the clot.
• Most cases are idiopathic thrombocytopenia (antibody mediated)
• Relief by fresh whole blood transfusions that contain large
numbers of platelets. Also, splenectomy is often helpful.
 Aspirin
• Causes most common disorder of platelet
function
• Blocks one of the steps required for platelets to
stick together. Effect makes effective for
disorders of blood clotting or thrombosis.
• does not totally paralyze the platelet, so people
take daily aspirin and have no problems with
bleeding.