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PLATELET AND HEMOSTASIS Dr. Zahoor Lecture - 6 HMIM BLOCK 224 1

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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 12

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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 27

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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