HMIM BLOCK 224
PLATELET AND
HEMOSTASIS
Dr. Zahoor
Lecture - 6
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Objectives
 Define hemostasis
 Platelet production and function
 Describe platelet aggregation
 Describe blood coagulation pathways
 Describe the mechanism of fibrinolysis and repair
 Summarize some common hemostatic disorders
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Platelets
• Platelets are cell fragments Formed in bone marrow
from megakaryocytes
•Platelet lack nuclei
• Normal count 150-350,000 /mm3
• Platelet diameter 2-4 m
• Life span 8-12 days
• Stored in spleen (30%)
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Platelets
 Active cytoplasm
 Cytoplasm has Actin + myosin
 Enzyme synthesis + storage of calcium
 Synthesis of prostaglandins
 Dense granules containing ADP, Thromboxine II, serotonin
- Liver produces hormone thrombopoietin which increases the
number of platelets
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Platelets
Membrane
- coat of glycoproteins
adhesion to injured area
- phospholipids
activation of intrinsic pathway of coagulation
- adenylate cyclase
cAMP
activate other platelets
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Hemopoiesis
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DEVELOPMENT OF PLATELET
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Hemostasis
• Hemostasis refers to the stoppage of
bleeding
• Actions that limit or prevent blood loss
include:
1. Blood vessel spasm
2. Platelet plug formation
3. Blood coagulation
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Hemostasis
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Coagulation Factors
Liver and
Endothelial cell
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1. Blood Vessel Spasm
1. Blood vessel spasm
•Triggered by pain receptors
(vasoconstrictor release from nerve ending)
•Damaged endothelium releases endothelin
that constrict the vessels
•Smooth muscle in blood vessel contracts
•Platelet release serotonin( vasoconstrictor)
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2. Stages of platelet plug formation
1.
Platelet adhesion
2. Platelet activation


ADP
Thromboxane formation (TXA2)
Both cause platelet aggregation
3. Platelet aggregation leads to platelet plug
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Platelet Plug Formation
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3. Blood Coagulation
3. Blood coagulation
• A blood clot forms via series of
reactions
• Blood coagulation mechanism are
1. Intrinsic pathway
2. Extrinsic pathway
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Clotting Cascade
 Series of steps involving 12 plasma clotting factors
that lead to final conversion of fibrinogen into a
stabilized fibrin mesh
 Intrinsic pathway


Involves 7 separate steps
Starts 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
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Blood Coagulation
See Intrinsic Pathway
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Clotting Cascade
Extrinsic pathway




Requires only 4 steps
Requires contact with tissue factors external to
the blood
Tissue thromboplastin – Factot III released
from traumatized tissue directly activates
factor X
Factor III and factor VII are required
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Blood Coagulation
See Extrinsic Pathway
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Clot Pathways
Intrinsic and Extrinsic
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Clot under
microscope
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SUMMARY
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what are the factors that prevent
blood clotting in healthy
person ?
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Factors that prevent a blood coagulation in
healthy person
• The smooth lining of blood vessels
discourages the accumulation of platelets
and clotting factors
 Endothelium releases many factors that act as anti
thrombotic and anticoagulant
Intact endothelium releases
 Prostacyclin(PGI2) ADP
dephosphatase
Inhibits
platelet
aggregation
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Factors that prevent a blood coagulation in
healthy person
 Plasmin – plasma protein produced by
liver, is present in blood in an inactive
form plasminogen
 tPA – Tissue plasminogen activator from
tissue converts plasminogen to plasmin
which causes degradation of fibrin
 Applied – tPA genetically engineered is
used in myocardial infarction to dissolve
thrombus in coronary artery
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Factors that prevent a blood
coagulation in healthy person
 Heparin sulphate – bind and activate
antithrombin III.
Antithrombin III inactivate thrombin.
- Some cells such as basophils and mast
cells secrete heparin (an anticoagulant)
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Fate of Blood Clots
• After a blood clot forms it retracts and pulls
the edges of a broken blood vessel together
while squeezing the fluid serum from the
clot
•Platelet-derived growth factor stimulates
smooth muscle cells and fibroblasts to repair
damaged blood vessel walls
•Plasmin digests the blood clots
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Important
• A thrombus is an abnormal blood clot inside the
blood vessel
• An embolus is a blood clot moving through the blood
vessels
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Abnormal Blood Clotting
 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
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Coagulation Defects
I. Hepatic failure
almost all clotting factors are made in the liver
II. Vitamin K deficiency
required for II (prothrombin), VII, IX, and X
III. Hemophilia
Factor VIII (hemophilia A 1/10,000),
IV. Factor IX (hemophilia B 1/100,000)
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Bleeding Disorder - Thrombocytopenia
 Thrombocytopenia (decrease
platelet)
There is bleeding in small
capillaries and blood vessels,
mucosa, skin
 ITP Idiopathic
thrombocytopenic purpura autoimmune (common)
 PURPURIC SPOTS ON
SKIN : minute hemorrhages
in subcutaneous tissue
Thrombocytopenic Purpura
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Hemophilia
 It is an X-linked disorder resulting from a deficiency in
factor VIII
 Hemophilia A is classic hemophilia (a disease referring to
the inability to clot blood).
 Individuals with deficiencies in factor VIII suffer
 Joint and muscle hemorrhage,
 Easy bruising and
 Prolonged bleeding occurs from wounds.
 Treatment of hemophilia A is accomplished by infusion of
factor VIII concentrates prepared from either human
plasma or by recombinant DNA technology.
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HEMOPHILIA
It’s a X linked
recessive disease
Females are carriers
Male suffer from
disease.
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Hemophilia B
 Hemophilia B results from deficiencies in factor IX.
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Thank you
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