Module 15 Introduction to Normal Haemostasis Acknowledgments Ministry of Health Guyana Centers for Disease Control and Prevention CDC Global AIDS Program GAP Guyana Centers for Disease Control and Prevention CDC Atlanta American Society for Clinical Pathology ASCP Learning Objectives After the completion of this unit of instruction the student will be able to Define hemostasis and explain the general interaction of the four 4 primary facets blood vessels platelets plasma coagulation factors and fibrinolysis Differentiate between primary and secondary hemostasis and the types of bleeding patterns associated with each Explain the functions of the vascular system Learning Objectives Discuss the physiological role of platelets in hemostasis including platelet plug formation and the role of platelets in maintaining normal vascular integrity Identify the ultrastructural zones in the platelet their major components and function Describe the series of morphologic and functional changes that occur in platelets following physiologic stimulation adhesion aggregation stabilization of vascular integrity and fibrin clot formation Learning Objectives Explain the interplay of the vasculature and platelets in the process of forming a hemostatic plug List the coagulation factors using both the Roman numeral common name and any synonyms Discuss the physiological role of the coagulation phase within the hemostatic mechanism Diagram and describe the intrinsic extrinsic and common pathway mechanisms of coagulation including all factors involved in the reactions Learning Objectives Explain the interplay of the coagulation system with the vascular and platelet systems to form a hemostatic plug Define fibrinolysis Discuss the physiological role of the fibrinolytic system List the four 4 main components of the fibrinolytic system and the function of each Learning Objectives Describe biochemical inhibitors important in the hemostatic process Identify the role of the protime PT and activated partial thromboplastin time APTT in assessing secondary hemostasis Name the vitamin K dependent factors Haemostasis Haemostasis is the process by which the body spontaneously stops bleeding and maintains blood in the fluid state within the vascular system Haemostatic Systems Vascular Platelets Coagulation Fibrinolytic Types of Haemostatis Primary and Secondary Primary Response of platelets and blood vessels to injury Abnormalities of Primary Hameostasis Mucous membrane and skin bleeding Secondary Haemostasis Process that transforms circulating blood into an insoluble gel Fibrinogen converted to fibrin Abnormalities of Secondary Haemostasis May involve deep tissue bleeding Evaluating Disorders of Haemostasis Family history Patient history Laboratory testing Haemostasis Vascular System Structure Function Composition Endothelial Cell Surface Inert to coagulation factors and platelets Nonwettable Vascular System Structure Basement membrane or subendothelium Submembranous tissue Vascular System Functions Vasoconstriction Diversion of blood flow Initiation of platelet activation Initiation of coagulation Composition of the Vascular System Prostacyclin Inhibits platelet aggregation ADP Promotes platelet aggregation Composition of the Vascular System Tissue thromboplastin tissue factor Initiates fibrin formation Von Willebrand Factor Facilitates platelet adhesion by bridging endothelium to platelet membrane receptor glycoprotein Ib GpIb Composition of the Vascular System Factor V Activates prothrombin in the coagulation system Thrombomodulin Inhibits thrombin Composition of the Vascular System Plasminogen activators Initiate fibrinolysis Heparin sulfate Helps activate antithrombin Platelet Overview Structure and Function Platelet Structure Three zones with unique functions Peripheral Sol gel Organelle Platelet Structure Peripheral zone Stimulus receptor and transmitter region Peripheral Zone Glycocalyx Surface coat Consists of glycoproteins Functions of the Glycocalyx Glycoproteins ABO blood group specificity Tissue compatibility Platelet antigenicity Transmission receptors Peripheral Zone Glycocalyx Platelet membrane Phospholipid bilayer Functions of the Platelet Membrane Receptors GpIb GpIIb IIIa Aggregating agents Platelet Factors PF3 PF4 Arachidonic acid Peripheral Zone Glycocalyx Platelet membrane Open canalicular system OCS Passageways surface to link internal environment with Open Canalicular System OCS Release of stored products Provides large surface area Peripheral Zone Glycocalyx Platelet membrane OCS Submembranous region Specialized microfilaments Platelet Structure Peripheral zone Sol gel zone Cytoskeletal and contractile region Sol Gel Zone Microtubules Surround circumference of platelet Monitor and regulate platelet responses Microfilaments Dispersed in cytoplasm Contain contractile proteins Reorient when platelets activated Help contribute to platelet shape change that occurs when platelets are stimulated Organelle Zone Granules Alpha Most numerous Contain platelet specific proteins and plasma proteins Organelle Zone Granules Alpha Dense bodies Fewer Appear densely opaque with TEM Dense Bodies Contain ADP ATP Calcium Catecholamines Other substances Organelle Zone Granules Alpha Dense bodies Lysosomes Glycogen Organelle Zone Granules Dense tubular system DTS DTS of Organelle Zone of Platelets Storage site for calcium Site of thromboxane and prostaglandin synthesis Organelle Zone Granules DTS Mitochondria 10 60 platelet Generate energy for platelet functions Platelet Function Maintain vascular integrity Nurture endothelial cells Fill in endothelial gaps Form a primary platelet plug Forming a Primary Platelet Plug The AAA reaction Adhere Activate Aggregate Adhesion Platelets stick to exposed subendothelial surface Dependent on GpIb and vWF Activation Platelet shape change Release reaction Contents of granules released Initiate aggregation Activation Platelet shape change Induced by many stimulants Strong stimulus promotes release reaction Aggregation Platelets stick to each other Primary or reversible Initially induced by ADP Secondary Irreversible Aggregation Primary Secondary Mechanism Calcium Fibrinogen GpIIb IIIa Aggregation Primary Secondary Mechanism Amplification and regulation Amplification and Regulation of Aggregation Phospholipase activation frees arachidonic acid Cyclo oxygenase converts arachidonic acid to prostaglandin endoperoxides Pathways of Endoperoxide Metabolism Thromboxane synthetase
View Full Document
Unlocking...