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Platelets
Dr. Sai Sailesh Kumar G
Associate Professor
Department of Physiology
RDGMC
DR Sai Sailesh Kumar G 1
A 40 year old male reports of extreme
tiredness, difficulty in concentration, feeling
of fainting on sudden standing and decrease
in appetite. Examination of oral cavity
revealed signs of red beefy tongue, bleeding
gums and cracking at the angles of mouth.
Peripheral smear showed macrocytic
hypochromic anemia. What is the diagnosis?
DR Sai Sailesh Kumar G 2
Learning objectives
 Describe the development and morphology of
platelets
 List and describe platelet functions
 Describe early events in hemostasis and the
formation of the platelet plug
 Describe thrombocytopenia
 Define bleeding time
 Describe thromboembolic conditions and
principles of their treatment
DR Sai Sailesh Kumar G 3
Hemostasis events
 The term hemostasis means prevention of blood
loss
 Whenever a vessel is severed, hemostasis is
achieved by several mechanisms
1. Vascular constriction
2. Formation of platelet plug
3. Formation of blood clot as a result of blood
coagulation
4. Growth of fibrous tissue into the blood clot to close
the hole in the vessel permanently
DR Sai Sailesh Kumar G 4
Vascular constriction
 Immediately after blood vessel ruptured
 Smooth muscle in the wall of the vessel contracts
 Reduces blood flow from the ruptured vessel
 The contraction results from
1. Local myogenic spasm
2. Local autacoid factors from platelets
3. Nervous reflexes
 More vasoconstriction results from myogenic spasm
 Platelets are responsible for much of the
vasoconstriction
 Vasoconstrictor released – thromboxane A2
DR Sai Sailesh Kumar G 5
Vasoconstriction
 The more severely a vessel is traumatized, the
greater is the degree of vascular spasm
 Spasm can last for many minutes or even hours
 During which time the processes of platelet plug
and blood coagulation occurs
DR Sai Sailesh Kumar G 6
Formation of platelet plug
 If the cut in the blood vessel is very small
 The cut is sealed by a platelet plug itself rather
than blood clot
DR Sai Sailesh Kumar G 7
Blood coagulation
 The clot begins to develop in 15-20 seconds if
the trauma to the vascular wall is severe
 If the trauma is minor, the clot begins in 1-2
minutes
 Clotting process is initiated by activator
substance
1. From damaged vessel wall
2. From platelets
3. From blood proteins
DR Sai Sailesh Kumar G 8
Blood coagulation
 Within 3-6 minutes after rupture of a vessel, the
entire opening of the vessel is filled with clot if
the opening is not too large
 After 20 minutes to an hour, the clot retracts
which closes the vessel further
 Platelets also plays major role in clot retraction
DR Sai Sailesh Kumar G 9
DR Sai Sailesh Kumar G 10
Physical and chemical characteristics of
platelets
 Platelets also called thrombocytes
 Minute discs with 1-4 micrometer in diameter
 Formed in the bone marrow from megakaryocytes
 Megakaryocytes fragment into minute platelets in
the bone marrow or soon after entering the blood
especially as they squeeze through capillaries
 Normal count – 150,000 – 300,000/ microlitre
 Can not reproduce
 Do not have nuclei
DR Sai Sailesh Kumar G 11
Physical and chemical characteristics of
platelets
 Platelets cell membrane has
1. Coat of glycoproteins
2. That helps for adherence to the injured areas of
blood vessel, especially to endothelial cells
3. Also have phospholipids – activate multiple
stages of blood coagulation process
DR Sai Sailesh Kumar G 12
Physical and chemical characteristics of
platelets
 Platelets cytoplasm has
1. Actin and myosin molecules – contractile proteins
2. Thrombosthenin – contractile protein – cause platelets to
contract
3. Residuals of both endoplasmic reticulum and golgi complex
that synthesize enzymes and store calcium ions
4. Mitochondria and enzyme systems that forms ATP and ADP
5. Enzymes that synthesize prostaglandlins – local hormones –
cause vascular and tissue reactions
6. Fibrin stabilizing factor
7. Growth factor – promotes cellular growth that repairs
damaged vessel
DR Sai Sailesh Kumar G 13
Physical and chemical characteristics of
platelets
 Platelet is an active structure
 Half life in blood – 8 to 12 days
 It functions several weeks
 It is eliminated from circulation mainly by tissue
macrophage system
 More than one half of platelets are removed by
macrophages in the spleen
DR Sai Sailesh Kumar G 14
Physical and chemical characteristics of
platelets
DR Sai Sailesh Kumar G 15
Mechanism of the platelet Plug
 Platelet repair of vascular openings is based on
several important functions of the platelet.
 When platelets come in contact with a damaged
vascular surface (collagen fibers in the vascular
wall), they rapidly change their own
characteristics drastically.
 They begin to swell, assume irregular forms with
numerous irradiating pseudopods protuding
from their surfaces.DR Sai Sailesh Kumar G 16
Mechanism of the platelet Plug
 Their contractile proteins contract forcefully and
cause the release of granules containing
multiple active factors.
 Further they become sticky and adhere to
collagen in the tissues and to a protein called
Von Willebrand factor, leaks into the traumatized
tissue from the plasma.
 They secrete large quantities of ADP and their
enzymes from thromboxane A2.
DR Sai Sailesh Kumar G 17
Mechanism of the platelet Plug
 These in turn act on nearby platelets to active them
as well.
 The stickiness of these additional platelets causes
them to adhere to the original activated platelets.
 Thus, at the site of puncture in a blood vessel wall,
the damaged vascular wall activates successively
increasing the number of platelets, further attract
more and more additional platelets, forming a
platelet plug.
DR Sai Sailesh Kumar G 18
Mechanism of the platelet Plug
 This plug is loose at first and usually blocks the
blood loss if the vascular opening is small.
 During these subsequent process of blood
coagulation, fibrin threads are formed.
 They attach tightly to the platelets, thus
constructing an unyielding plug.
DR Sai Sailesh Kumar G 19
Importance of platelet Mechanism for
closing vascular holes
 The platelet-plugging mechanism is extremely important for
closing minute ruptures in very small blood vessels that
occurs thousands of times in a day.
 Multiple small holes through the endothelial cells themselves
are often closed by platelets actually fuse with the endothelial
cells to form additional endothelial cell membrane.
 Literally, thousands of small hemorrhagic areas develop each
day under the skin and throughout the internal tissues of a
person who has few blood platelets. (Purpura)
 This phenomenon does not occur in persons with normal
numbers of platelets.
DR Sai Sailesh Kumar G 20
Thrombocytopenia
 Means the presence of very low numbers of platelets in
the circulating blood.
 People with thromocytopenia have a tendency to bleed,
as do hemophiliacs.
 Difference is that the bleeding is from many small
venules or capillaries, rather than from large vessels, as
in hemophilia.
 As a result small punctate hemorrhages occur
throughout all the body tissues.
 The skin of such person displays many small, purplish
blotches named as thrombocytopenic purpura.
DR Sai Sailesh Kumar G 21
Thrombocytopenia
 Usually, bleeding will not occur until the platelets in the
blood falls below 50,000/µL (Normal: 1,50,000- 3,00,000).
 Levels as low as 10,000/µL are frequently lethal.
 One can suspect the existence of thrombocytopenia if
the person’s blood clot fails to retract, even without
making platelet counts in the blood.
 As pointed out earlier clot retraction is normally
dependent on release of multiple coagulation factors
from the large number of platelets entrapped in the fibrin
mesh of the clot.
DR Sai Sailesh Kumar G 22
Thrombocytopenia
 Most people with thrombocytopenia have the disease known
as idiopathic thrombocytopenia meaning thrombocytopenia
of unknown cause.
 It is observed that due to certain unknown reasons, specific
antibodies had formed and react against the platelets to
destroy them.
 By giving fresh whole blood transfusions containing large
numbers of platelets for a patient with thrombocytopenia may
give relief from bleeding for 1-4 days.
 Splenectomy is often helpful- may even give complete cure
because spleen normally removes large number of platelets
from blood.
DR Sai Sailesh Kumar G 23
Thromboembolic conditions
 Thrombo and Emboli- an abnormal clot that develops in
a blood vessel is called a thrombus.
 Freely flowing clots are known as emboli. ( once the clot
has developed, continued the flow of blood past the clot
is likely to break it away from its attachment and cause
the clot to flow with the blood).
 Emboli that originate in large arteries or in the left side of
the heart can flow peripherally and plug arteries or
arterioles in the brain, kidneys, or elsewhere.
 Emboli that originate in the venous system or in the right
side of the heart generally flow into the lungs to cause
pulmonary arterial embolism.
DR Sai Sailesh Kumar G 24
Cause of Thromboembolic conditions
 Two fold causes:
1) Any roughened endothelial surface of a vessel-
may caused by arteriosclerosis, infection, or
trauma-is likely to initiate the clotting process.
2) Blood often clots when it flows very slowly
through blood vessels
DR Sai Sailesh Kumar G 25
Use of t-PA in treating intravascular clots
 Genetically engineered tissue plasminogen activator
(t-PA) when delivered through a catheter to an area
with a thrombus, it is effective in activating
plasminogen to plasma.
 This in turn will dissolve some intravascular clots.
 For instant, if used within the first hour or so after
thromboitic occlusion of a coronary artery or after a
stroke, the heart and the brain are often spared
serious damage.
DR Sai Sailesh Kumar G 26
Femoral Venous Thrombosis and
Massive Pulmonary Embolism
 Because clotting almost always occur when blood flow is
blocked for many hours in any vessel of the body.
 The immobility of patients confined to bed plus the
practice of propping the knees with pillows often causes
intravascular clotting because of blood stasis in one or
more of the leg veins for hours at a time.
 Then the clot grows mainly in the direction of the slowly
moving venous blood, sometimes growing the entire
length of the leg veins.
 Occasionally it may even grow up into the common iliac
vein and inferior vena cava.
DR Sai Sailesh Kumar G 27
Femoral Venous Thrombosis and
Massive Pulmonary Embolism
 About 1 out 10 times, a large part of the clot disengages from
its attachments to the vessel wall and flows freely with the
venous blood through the right side of the heart and into
pulmonary arteries to cause massive blockage called massive
pulmonary embolism.
 If the clot is large enough to occlude both pulmonary arteries
at the same time, immediate death ensues.
 If only one pulmonary artery is blocked, death may not occur,
but the embolism may lead to death a few hours to several
days later.
 Because of further growth of the clot within the pulmonary
vessels.
 However, t-PA therapy can be a lifesaver.
DR Sai Sailesh Kumar G 28
Werner Frossmann- Invention of
catheterization
DR Sai Sailesh Kumar G 29
Bleeding time
 When a sharp-pointed knife is used to pierce the
tip of the finger or lobe of the ear, bleeding
ordinarily lasts for 1-6 minutes.
 The time depends largely on the depth of the
wound and the degree of hyperemia in the finger
or earlobe at the time of the test.
 Lack of any one of several clotting factors can
prolong the bleeding time, but it is especially
prolonged by lack of platelets.
DR Sai Sailesh Kumar G 30
DR Sai Sailesh Kumar G 31
THANK YOU
DR Sai Sailesh Kumar G 32

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Platelets

  • 1. Platelets Dr. Sai Sailesh Kumar G Associate Professor Department of Physiology RDGMC DR Sai Sailesh Kumar G 1
  • 2. A 40 year old male reports of extreme tiredness, difficulty in concentration, feeling of fainting on sudden standing and decrease in appetite. Examination of oral cavity revealed signs of red beefy tongue, bleeding gums and cracking at the angles of mouth. Peripheral smear showed macrocytic hypochromic anemia. What is the diagnosis? DR Sai Sailesh Kumar G 2
  • 3. Learning objectives  Describe the development and morphology of platelets  List and describe platelet functions  Describe early events in hemostasis and the formation of the platelet plug  Describe thrombocytopenia  Define bleeding time  Describe thromboembolic conditions and principles of their treatment DR Sai Sailesh Kumar G 3
  • 4. Hemostasis events  The term hemostasis means prevention of blood loss  Whenever a vessel is severed, hemostasis is achieved by several mechanisms 1. Vascular constriction 2. Formation of platelet plug 3. Formation of blood clot as a result of blood coagulation 4. Growth of fibrous tissue into the blood clot to close the hole in the vessel permanently DR Sai Sailesh Kumar G 4
  • 5. Vascular constriction  Immediately after blood vessel ruptured  Smooth muscle in the wall of the vessel contracts  Reduces blood flow from the ruptured vessel  The contraction results from 1. Local myogenic spasm 2. Local autacoid factors from platelets 3. Nervous reflexes  More vasoconstriction results from myogenic spasm  Platelets are responsible for much of the vasoconstriction  Vasoconstrictor released – thromboxane A2 DR Sai Sailesh Kumar G 5
  • 6. Vasoconstriction  The more severely a vessel is traumatized, the greater is the degree of vascular spasm  Spasm can last for many minutes or even hours  During which time the processes of platelet plug and blood coagulation occurs DR Sai Sailesh Kumar G 6
  • 7. Formation of platelet plug  If the cut in the blood vessel is very small  The cut is sealed by a platelet plug itself rather than blood clot DR Sai Sailesh Kumar G 7
  • 8. Blood coagulation  The clot begins to develop in 15-20 seconds if the trauma to the vascular wall is severe  If the trauma is minor, the clot begins in 1-2 minutes  Clotting process is initiated by activator substance 1. From damaged vessel wall 2. From platelets 3. From blood proteins DR Sai Sailesh Kumar G 8
  • 9. Blood coagulation  Within 3-6 minutes after rupture of a vessel, the entire opening of the vessel is filled with clot if the opening is not too large  After 20 minutes to an hour, the clot retracts which closes the vessel further  Platelets also plays major role in clot retraction DR Sai Sailesh Kumar G 9
  • 10. DR Sai Sailesh Kumar G 10
  • 11. Physical and chemical characteristics of platelets  Platelets also called thrombocytes  Minute discs with 1-4 micrometer in diameter  Formed in the bone marrow from megakaryocytes  Megakaryocytes fragment into minute platelets in the bone marrow or soon after entering the blood especially as they squeeze through capillaries  Normal count – 150,000 – 300,000/ microlitre  Can not reproduce  Do not have nuclei DR Sai Sailesh Kumar G 11
  • 12. Physical and chemical characteristics of platelets  Platelets cell membrane has 1. Coat of glycoproteins 2. That helps for adherence to the injured areas of blood vessel, especially to endothelial cells 3. Also have phospholipids – activate multiple stages of blood coagulation process DR Sai Sailesh Kumar G 12
  • 13. Physical and chemical characteristics of platelets  Platelets cytoplasm has 1. Actin and myosin molecules – contractile proteins 2. Thrombosthenin – contractile protein – cause platelets to contract 3. Residuals of both endoplasmic reticulum and golgi complex that synthesize enzymes and store calcium ions 4. Mitochondria and enzyme systems that forms ATP and ADP 5. Enzymes that synthesize prostaglandlins – local hormones – cause vascular and tissue reactions 6. Fibrin stabilizing factor 7. Growth factor – promotes cellular growth that repairs damaged vessel DR Sai Sailesh Kumar G 13
  • 14. Physical and chemical characteristics of platelets  Platelet is an active structure  Half life in blood – 8 to 12 days  It functions several weeks  It is eliminated from circulation mainly by tissue macrophage system  More than one half of platelets are removed by macrophages in the spleen DR Sai Sailesh Kumar G 14
  • 15. Physical and chemical characteristics of platelets DR Sai Sailesh Kumar G 15
  • 16. Mechanism of the platelet Plug  Platelet repair of vascular openings is based on several important functions of the platelet.  When platelets come in contact with a damaged vascular surface (collagen fibers in the vascular wall), they rapidly change their own characteristics drastically.  They begin to swell, assume irregular forms with numerous irradiating pseudopods protuding from their surfaces.DR Sai Sailesh Kumar G 16
  • 17. Mechanism of the platelet Plug  Their contractile proteins contract forcefully and cause the release of granules containing multiple active factors.  Further they become sticky and adhere to collagen in the tissues and to a protein called Von Willebrand factor, leaks into the traumatized tissue from the plasma.  They secrete large quantities of ADP and their enzymes from thromboxane A2. DR Sai Sailesh Kumar G 17
  • 18. Mechanism of the platelet Plug  These in turn act on nearby platelets to active them as well.  The stickiness of these additional platelets causes them to adhere to the original activated platelets.  Thus, at the site of puncture in a blood vessel wall, the damaged vascular wall activates successively increasing the number of platelets, further attract more and more additional platelets, forming a platelet plug. DR Sai Sailesh Kumar G 18
  • 19. Mechanism of the platelet Plug  This plug is loose at first and usually blocks the blood loss if the vascular opening is small.  During these subsequent process of blood coagulation, fibrin threads are formed.  They attach tightly to the platelets, thus constructing an unyielding plug. DR Sai Sailesh Kumar G 19
  • 20. Importance of platelet Mechanism for closing vascular holes  The platelet-plugging mechanism is extremely important for closing minute ruptures in very small blood vessels that occurs thousands of times in a day.  Multiple small holes through the endothelial cells themselves are often closed by platelets actually fuse with the endothelial cells to form additional endothelial cell membrane.  Literally, thousands of small hemorrhagic areas develop each day under the skin and throughout the internal tissues of a person who has few blood platelets. (Purpura)  This phenomenon does not occur in persons with normal numbers of platelets. DR Sai Sailesh Kumar G 20
  • 21. Thrombocytopenia  Means the presence of very low numbers of platelets in the circulating blood.  People with thromocytopenia have a tendency to bleed, as do hemophiliacs.  Difference is that the bleeding is from many small venules or capillaries, rather than from large vessels, as in hemophilia.  As a result small punctate hemorrhages occur throughout all the body tissues.  The skin of such person displays many small, purplish blotches named as thrombocytopenic purpura. DR Sai Sailesh Kumar G 21
  • 22. Thrombocytopenia  Usually, bleeding will not occur until the platelets in the blood falls below 50,000/µL (Normal: 1,50,000- 3,00,000).  Levels as low as 10,000/µL are frequently lethal.  One can suspect the existence of thrombocytopenia if the person’s blood clot fails to retract, even without making platelet counts in the blood.  As pointed out earlier clot retraction is normally dependent on release of multiple coagulation factors from the large number of platelets entrapped in the fibrin mesh of the clot. DR Sai Sailesh Kumar G 22
  • 23. Thrombocytopenia  Most people with thrombocytopenia have the disease known as idiopathic thrombocytopenia meaning thrombocytopenia of unknown cause.  It is observed that due to certain unknown reasons, specific antibodies had formed and react against the platelets to destroy them.  By giving fresh whole blood transfusions containing large numbers of platelets for a patient with thrombocytopenia may give relief from bleeding for 1-4 days.  Splenectomy is often helpful- may even give complete cure because spleen normally removes large number of platelets from blood. DR Sai Sailesh Kumar G 23
  • 24. Thromboembolic conditions  Thrombo and Emboli- an abnormal clot that develops in a blood vessel is called a thrombus.  Freely flowing clots are known as emboli. ( once the clot has developed, continued the flow of blood past the clot is likely to break it away from its attachment and cause the clot to flow with the blood).  Emboli that originate in large arteries or in the left side of the heart can flow peripherally and plug arteries or arterioles in the brain, kidneys, or elsewhere.  Emboli that originate in the venous system or in the right side of the heart generally flow into the lungs to cause pulmonary arterial embolism. DR Sai Sailesh Kumar G 24
  • 25. Cause of Thromboembolic conditions  Two fold causes: 1) Any roughened endothelial surface of a vessel- may caused by arteriosclerosis, infection, or trauma-is likely to initiate the clotting process. 2) Blood often clots when it flows very slowly through blood vessels DR Sai Sailesh Kumar G 25
  • 26. Use of t-PA in treating intravascular clots  Genetically engineered tissue plasminogen activator (t-PA) when delivered through a catheter to an area with a thrombus, it is effective in activating plasminogen to plasma.  This in turn will dissolve some intravascular clots.  For instant, if used within the first hour or so after thromboitic occlusion of a coronary artery or after a stroke, the heart and the brain are often spared serious damage. DR Sai Sailesh Kumar G 26
  • 27. Femoral Venous Thrombosis and Massive Pulmonary Embolism  Because clotting almost always occur when blood flow is blocked for many hours in any vessel of the body.  The immobility of patients confined to bed plus the practice of propping the knees with pillows often causes intravascular clotting because of blood stasis in one or more of the leg veins for hours at a time.  Then the clot grows mainly in the direction of the slowly moving venous blood, sometimes growing the entire length of the leg veins.  Occasionally it may even grow up into the common iliac vein and inferior vena cava. DR Sai Sailesh Kumar G 27
  • 28. Femoral Venous Thrombosis and Massive Pulmonary Embolism  About 1 out 10 times, a large part of the clot disengages from its attachments to the vessel wall and flows freely with the venous blood through the right side of the heart and into pulmonary arteries to cause massive blockage called massive pulmonary embolism.  If the clot is large enough to occlude both pulmonary arteries at the same time, immediate death ensues.  If only one pulmonary artery is blocked, death may not occur, but the embolism may lead to death a few hours to several days later.  Because of further growth of the clot within the pulmonary vessels.  However, t-PA therapy can be a lifesaver. DR Sai Sailesh Kumar G 28
  • 29. Werner Frossmann- Invention of catheterization DR Sai Sailesh Kumar G 29
  • 30. Bleeding time  When a sharp-pointed knife is used to pierce the tip of the finger or lobe of the ear, bleeding ordinarily lasts for 1-6 minutes.  The time depends largely on the depth of the wound and the degree of hyperemia in the finger or earlobe at the time of the test.  Lack of any one of several clotting factors can prolong the bleeding time, but it is especially prolonged by lack of platelets. DR Sai Sailesh Kumar G 30
  • 31. DR Sai Sailesh Kumar G 31
  • 32. THANK YOU DR Sai Sailesh Kumar G 32