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- PLATELET AND HEMOSTASIS Dr. Zahoor Lecture - 6 HMIM BLOCK 224
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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 2
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- Platelets Platelets are cell fragments Formed in bone marrow
from megakaryocytes Platelet lack nuclei Normal count 150-350,000
/mm 3 Platelet diameter 2-4 m Life span 8-12 days Stored in spleen
(30%) 3
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- 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 4
Platelets
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- Membrane - coat of glycoproteins adhesion to injured area -
phospholipids activation of intrinsic pathway of coagulation -
adenylate cyclase cAMP activate other platelets Platelets 5
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- Hemopoiesis 6
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- DEVELOPMENT OF PLATELET 7
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- Hemostasis 8 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 9
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- 10 Coagulation Factors Liver and Endothelial cell
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- 1. Blood Vessel Spasm 11 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 (TX A2 ) Both cause
platelet aggregation 3. Platelet aggregation leads to platelet plug
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- Platelet Plug Formation 13
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- 3. Blood Coagulation 14 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 15
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- Blood Coagulation 16 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 17
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- 18 Blood Coagulation See Extrinsic Pathway
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- 19 Clot Pathways Intrinsic and Extrinsic
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- Clot under microscope 20
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- SUMMARY 21
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- what are the factors that prevent blood clotting in healthy
person ? 22
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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(PGI 2 )- ADP dephosphatase 23 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 24
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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) 25
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- Fate of Blood Clots 26 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 30
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- 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) Coagulation Defects 31
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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 32 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. 33
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- HEMOPHILIA Its a X linked recessive disease Females are
carriers Male suffer from disease. 34
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- Hemophilia B Hemophilia B results from deficiencies in factor
IX. 35
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- Thank you 36