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PLATELET AND HEMOSTASIS

Dr. ZahoorLecture - 6 HMIM BLOCK 224

1Objectives 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

2Platelets Platelets are cell fragments Formed in bone marrow from megakaryocytesPlatelet lack nuclei Normal count 150-350,000 /mm3 Platelet diameter 2-4 m Life span 8-12 days Stored in spleen (30%)

33Active cytoplasm

Cytoplasm has Actin + myosinEnzyme synthesis + storage of calciumSynthesis of prostaglandins Dense granules containing ADP, Thromboxine II, serotonin

Liver produces hormone thrombopoietin which increases the number of platelets 4Platelets

Membrane

- coat of glycoproteins adhesion to injured area - phospholipids activation of intrinsic pathway of coagulation - adenylate cyclase cAMP activate other plateletsPlatelets55Hemopoiesis6

DEVELOPMENT OF PLATELET7Hemostasis8 Hemostasis refers to the stoppage of bleeding Actions that limit or prevent blood loss include:1. Blood vessel spasm2. Platelet plug formation3. Blood coagulation

Hemostasis910Coagulation Factors

Liver and Endothelial cell1. Blood Vessel Spasm111. Blood vessel spasmTriggered 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)

112. Stages of platelet plug formationPlatelet adhesion

Platelet activationADPThromboxane formation (TXA2) Both cause platelet aggregation

Platelet aggregation leads to platelet plug12Platelet Plug Formation13

133. Blood Coagulation143. Blood coagulation A blood clot forms via series of reactions

Blood coagulation mechanism are 1. Intrinsic pathway 2. Extrinsic pathway 14Clotting Cascade Series of steps involving 12 plasma clotting factors that lead to final conversion of fibrinogen into a stabilized fibrin mesh Intrinsic pathwayInvolves 7 separate stepsStarts when factor XII (Hageman factor) is activated by coming into contact with exposed collagen in injured vessel or foreign surface such as glass test tube15Blood Coagulation16

See Intrinsic Pathway16Clotting Cascade Extrinsic pathwayRequires only 4 stepsRequires contact with tissue factors external to the bloodTissue thromboplastin Factot III released from traumatized tissue directly activates factor X Factor III and factor VII are required1718

Blood CoagulationSee Extrinsic Pathway18

19Clot Pathways Intrinsic and Extrinsic19Clot under microscope20

20SUMMARY21

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what are the factors that prevent blood clotting in healthy person ?22Factors 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

23Inhibits platelet aggregation Factors that prevent a blood coagulation in healthy person Plasmin plasma protein produced by liver, is present in blood in an inactive form plasminogentPA Tissue plasminogen activator from tissue converts plasminogen to plasmin which causes degradation of fibrinApplied tPA genetically engineered is used in myocardial infarction to dissolve thrombus in coronary artery

24Factors 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)

25Fate of Blood Clots26 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

26ImportantA 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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28Clinical Application2929Abnormal Blood ClottingThrombusAbnormal intravasculaar clot attached to a vessel wallEmboliFreely floating clotsFactors that can cause thromboembolismRoughened vessel surfaces associated with atherosclerosisImbalances in the clotting-anticlotting systemsSlow-moving blood 30I. Hepatic failurealmost all clotting factors are made in the liverII. Vitamin K deficiencyrequired for II (prothrombin), VII, IX, and XIII. HemophiliaFactor VIII (hemophilia A 1/10,000),

IV. Factor IX (hemophilia B 1/100,000)Coagulation Defects3131Bleeding Disorder - ThrombocytopeniaThrombocytopenia (decrease platelet) There is bleeding in small capillaries and blood vessels, mucosa, skinITP Idiopathic thrombocytopenic purpura - autoimmune (common)PURPURIC SPOTS ON SKIN : minute hemorrhages in subcutaneous tissue

32Thrombocytopenic Purpura32HemophiliaIt is an X-linked disorder resulting from a deficiency in factor VIIIHemophilia Ais 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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HEMOPHILIAIts a X linked recessive diseaseFemales are carriersMale suffer from disease.34Hemophilia BHemophilia Bresults from deficiencies in factor IX.

35Thank you36