PLATELETS, HEMOSTASIS
&
BLOOD COAGULATION
Learning objectives
• To know the role of platelets in hemostasis
• To understand the steps of hemostasis
• To know the pathways of coagulation or
clotting
• To be familiar with some abnormal clotting
conditions
PLATELETS
Hemopoiesis
Platelets (Thrombocytes)
• Thrombocytes:
• Cell fragments shed from megakaryocytes
– Lack nuclei
– Have organelles and cytosolic enzymes for generating energy and
synthesizing secretory products
– High concentrations of actin and myosin
• Remain functional for an average of 10 days
• Removed from circulation by tissue macrophages
• Do not leave blood as WBCs do
– About ⅓ are stored in blood-filled spaces in spleen
– Released when needed by sympathetically induced splenic contraction
• Thrombopoietin:
– Hormone produced by liver,
-- increases number of megakaryocytes and therefore increases platelet
production
Hemostasis
• Prevents blood loss from a broken blood vessel
• Involves 3 major steps
1) Vascular spasm
Reduces blood flow through a damaged vessel
2) Formation of a platelet plug
Platelets aggregate on contact with exposed collagen in
damaged wall of the vessel Platelets release ADP which causes
surface of nearby circulating platelets to become sticky in
order to adhere to first layer of aggregated platelets
3) Blood coagulation (clotting)
Transformation of blood from liquid into a solid gel
Much rarer occurrence of bleeding from mediumto large-size vessels usually cannot be stopped by
the body’s hemostatic mechanisms alone.
Bleeding from a severed artery is more profuse and
therefore more dangerous than venous bleeding.
First-aid measures for a severed artery include
applying external pressure to the wound.
Hemorrhage from a traumatized vein can often be
stopped simply by elevating the bleeding body part
or applying mild external compression is usually
adequate.
VASCULAR SPASM (Vasoconstriction):
A cut or torn blood vessel immediately constricts.
Vascular spasm reduces blood flow through an injured vessel by
a paracrine released locally from (endothelium) of the injured vessel.
This constriction, or vascular spasm, slows blood flow through the defect and
thus minimizes blood loss.
Also the opposing endothelial surfaces of the vessel are pressed together
and adhere to each other, further sealing off the damaged vessel.
These physical measures alone cannot completely prevent further blood
loss, but they minimize blood flow through the break in the vessel until the
other hemostatic measures can actually plug up the hole.
HEMOSTSTIC PLATELET PLUG
Platelets aggregate to form a plug at a vessel tear or cut.
Platelets normally do not stick to the smooth endothelial surface of blood
vessels, but when this lining is disrupted because of vessel injury, platelets
adhere to and are activated by the exposed collagen.
When platelets passing by in the blood are exposed to collagen, they
become adhered to the collagen by means of integrin,
This adhesion prevents these platelets from being swept forward in the
circulation.
This layer of stuck platelets forms the foundation of a hemostatic platelet
plug at the site of the defect.
Platelet plug
•
Thus formation of a platelet plug involves the three successive, closely integrated
events of;
•
adhesion ,
•
activation and
•
aggregation
Functions of aggregated platelets :
1) Actin-myosin complex contract to strengthen the loose plug
2) Release several powerful vasoconstrictors eg. Serotonin, epinephrine,
thromboxane A2
3) Platelet plug release chemicals like platelet factor3 (PF3) enhancing
blood clotting
CLOT FORMATION
CLOTTING FACTORS
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Factor I = Fibrinogen
Factor II = Prothrombin
Factor III = Tissue factor
Factor IV = Calcium
Factor V = Labile factor
Factor VI - Does not exist
Factor VII = Stable factor
Factor VIII = Antihemophilic factor A
Factor IX = Antihemophilic factor B or Christmas factor
Factor X = Stuart Prower factor
Factor XI = Antihemophilic factor C
Factor XII = Hageman factor
Factor XIII = Fibrin stabilising factor
Clot Formation
• Reinforces platelet plug and converts blood in
the vicinity of vessel injury into a non flowing
gel
• Clotting factors are always present in blood
plasma in inactive precursor form
– Vessel damage that exposes collagen initiates
cascade of reactions that involve successive
activation of clotting factors , finally
• Convert fibrinogen  fibrin by means of the intrinsic
clotting pathway
The original fibrin web is rather weak, because the fibrin strands are only
loosely interlaced. However, chemical linkages rapidly form between adjacent
strands to strengthen and stabilize the clot meshwork.
This cross-linkage process is catalyzed by a clotting factor known as factor XIII
(fibrin-stabilizing factor), which normally is present in the plasma in inactive
form.
Fibrin is the stretchiest natural protein. This highly elastic property accounts
for the extraordinary stretchiness of blood clots.
On average fibrin fibers can be passively stretched to 2.8 times their original
length and still snap back to their starting length and can be stretched to 4.3
times their original length before they break.
Clotting Cascade
• Series of steps involving 12 plasma clotting factors that lead to final
conversion of fibrinogen into a stabilized fibrin mesh
• May be triggered by
– Intrinsic pathway
• Involves seven separate steps
• Set off when factor XII (Hageman factor) is activated by coming into
contact with exposed collagen in injured vessel or foreign surface
such as glass test tube.
– Extrinsic pathway
• Requires only 4 steps
• Requires contact with tissue factors external to the blood
• Tissue thromboplastin (factor III) released from traumatized tissue
activate factor VII. Tissue thromboplastin and activated factor VII
activates factor X.
Clot Pathways
CLOT RETRACTION
• Once a clot is formed, contraction of platelets
within the clot shrinks the fibrin mesh, bringing
the edges of damage vessel close to each other.
• During clot retraction, fluid is squeezed from the
clot, thus making it semisolid & more strong.
• This fluid is SERUM, which is plasma minus
fibrinogen and other clotting factors that have
been removed during clotting.
Role of thrombin
FIBRINOLYSIS
• Fibrinolysis:
• means dissolution of excess of clot
• to prevent blockage of small blood vessels
Abnormal Blood Clotting
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Thrombus
– Abnormal intravasculaar clot attached to a vessel wall
Emboli
– Freely floating clots
Factors that can cause thromboembolism
– Roughened vessel surfaces associated with atherosclerosis
– Imbalances in the clotting-anticlotting systems
– Slow-moving blood
– Occasionally triggered by release of tissue thromboplastin into blood from
large amounts of traumatized tissue
EXCESSIV BLEEDING:
Hemophilia
– Excessive bleeding caused by deficiency of one of the factors in the
clotting cascade (factor VIII or IX)
– Hemophilia A - Def. of factor VIII
– Hemophilia B - Def. of factor IX
PURPURA
• occurs due to decrease in no. of
platelets(thrombocytopenia)
• Small pin point or dot capillary hemorrhages
are visible in the skin
• Vitamin K deficiency can cause bleeding
tendency, due to incomplete activation of vit.
K dependent factors (factors II, VII, IX and X)
HEMOPHILIA
Hemarthrosis
THANKS
WITH BEST WISHES