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

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

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%)

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

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

Hemopoiesis

DEVELOPMENT OF PLATELET

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

Hemostasis

Coagulation Factors Liver and Endothelial cell

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)

2. Stages of platelet plug formation Platelet adhesion Platelet activation ADP Thromboxane formation (TXA2) Both cause platelet aggregation Platelet aggregation leads to platelet plug

Platelet Plug Formation

3. Blood Coagulation 3. Blood coagulation A blood clot forms via series of reactions Blood coagulation mechanism are 1. Intrinsic pathway 2. Extrinsic pathway

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

Blood Coagulation See Intrinsic Pathway

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

Blood Coagulation See Extrinsic Pathway

Clot Pathways Intrinsic and Extrinsic

Clot under microscope

SUMMARY

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

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

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

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)

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

Important A thrombus is an abnormal blood clot inside the blood vessel An embolus is a blood clot moving through the blood vessels

Clinical Application

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

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)

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

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.

HEMOPHILIA It’s a X linked recessive disease Females are carriers Male suffer from disease.

Hemophilia B Hemophilia B results from deficiencies in factor IX.

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