<p> Normal Hemostasis: Objectives</p><p>1. Describe the roles of the normal hemostatic processes.</p><p> a. Vasoconstriction  Activation of the soluble coagulation system  fibrin clot (red thrombus)  Platelet stimulation  adhesion (usually to collagen) aggregation (of platelets)  Platelet plug (white thrombus)</p><p>2. Describe the two systems contributing to normal hemostasis.</p><p> a. The Soluble System (procoagulant proteins)</p><p> a.i. Proteins include:</p><p> a.i.1. Fibrinogen</p><p> a.i.2. Von Willebrand Factor (sticky glue for platelets)</p><p> b. The Cellular System (platelets)</p><p> b.i. Platelets</p><p> b.i.1. Suppliers of procoagulant proteins</p><p> b.i.2. Catalysts to reactions of the soluble coagulation system (stim. clotting)</p><p> b.i.3. Hemostasis, inflammatory response, tissue repair, and atherogenesis</p><p>3. Describe the normal production, structure, and function of platelets.</p><p> a. Production of platelets:</p><p> a.i. Pluripotent stem cell in bone marrow produces megokaryocyte</p><p> a.ii. Fragments off of the megokaryocyte’s cytoplasm</p><p> a.iii. Normal platelet count: 100,000-450,000/uL of blood</p><p> a.iv. Thrombopoietin: regulates megokaryocyte development and platelet prod.</p><p> a.iv.1. Primarily produced in the liver (a fraction is in the kidney)</p><p> b. Structure of platelets:</p><p> b.i. Contractile microfilaments extend thru submembranous space throughout the platelet cytoplasm</p><p> b.i.1. Responsible for dramatic shape changes which accompany platelet activation Normal Hemostasis: Objectives</p><p> b.ii. 4 types of granules:</p><p> b.ii.1. Alpha, dense, lysosomes, and peroxisomes</p><p> b.ii.2. Alpha-granules:</p><p> b.ii.2.a. Most abundant</p><p> b.ii.2.b. Contain both platelet specific and nonspecific peptides</p><p> b.ii.2.b.i. Contribute to and modulate coagulation inflammation, immunity, and tissue repair</p><p> b.ii.3. Dense-granules:</p><p> b.ii.3.a. Rich repositories of:</p><p> b.ii.3.a.i. Serotonin and ADP</p><p> b.ii.3.a.i.1. Leads to aggregation of platelets</p><p> b.ii.3.a.ii. ATP</p><p> b.ii.3.a.ii.1. Leads to anti-aggregation</p><p> b.ii.3.a.iii. Calcium</p><p> b.ii.3.a.iii.1. An essential coagulation factor</p><p> c. Function of platelets:</p><p> c.i. Hemostasis (promotion of immediate hemostasis)</p><p> c.i.1. By platelet adhesion and platelet aggregation (forms platelet plug)</p><p> c.ii. Inflammation response</p><p> c.iii. Tissue Repair</p><p> c.iii.1. Local release of vasocaonstrictors to decrease blood flow to injured area</p><p> c.iii.2. Catalysis of reaction of the soluble coagulation cascade leading to fibrin clot formation</p><p> c.iv. Atherogenesis</p><p>4. Describe the initial steps to evaluate the integrity of platelet structure and function. Normal Hemostasis: Objectives</p><p> a. Platelet count: part of the CBC (100,000-450,000 platelets/uL blood)</p><p> b. MPV (Platelet volume measurement)</p><p> b.i. Platelet volume increases when production accelerates</p><p> c. Platelet Function: whole blood platelet function or bleeding time</p><p> c.i. Assess coagulation effectiveness</p><p> d. Platelet aggregometry (expensive)</p><p>5. Explain the role of the vascular endothelium in normal hemostasis.</p><p> a. A vascular break or injury causes a hemostatic plug to form (platelet-fibrin meshwork)</p><p>6. Describe the intrinsic, extrinsic, and common pathways of coagulation being aware of which coagulation factors are a part of each pathway.</p><p> a. Intrinsic Pathway:</p><p> a.i. Components:</p><p> a.i.1. F XII (12)</p><p> a.i.1.a. Notices negatively charged surfaces, esp Collagen</p><p> a.i.1.a.i. Begins intrinsic cascade</p><p> a.i.2. F XI (11)</p><p> a.i.2.a. Activated by small amount of F XII</p><p> a.i.3. F IX (9)</p><p> a.i.4. F VIII (8) – low = hemophilia</p><p> a.i.5. PK (PreKallikrein) – inflammation</p><p> a.i.5.a. Leads to kaliikrein activation, which leads to HK activation</p><p> a.i.6. HK (high molecular weight Kininogen) – inflammation</p><p> a.i.6.a. Then: activation of blood coagulation, fibrinolysis, completment pathway, inflammation Normal Hemostasis: Objectives</p><p> b. Extrinsic Pathway:</p><p> b.i. The major pathway of activation of coagulation in vivo</p><p> b.ii. Components:</p><p> b.ii.1. Tissue Factor (TF, F III) factor 3</p><p> b.ii.1.a. Functions as a cofactor/receptor which (in presence of Ca) activates Factor VII</p><p> b.ii.2. Tissue factor inhibitor</p><p> b.ii.3. Plasma Factor VII (7)</p><p> b.ii.3.a. Requires vitamin K for synthesis</p><p> b.ii.4. Activated VII leads to Factor IX and (or straight to) Factor X activation</p><p> b.iii. Tissue Plasminogen Activator (t-PA)</p><p> b.iii.1. Inhibits clot formation by its release from endothelial cells</p><p> c. Common Pathway:</p><p> c.i. Prothrombin Complex (F X, F V in the presence of Ca)</p><p> c.i.1. Leads to Prothrombin FII  Thrombin (FII)</p><p> c.ii. Thrombin leads to: Fibrinogen  Fibrin </p><p> c.ii.1. Fibrin monomer (activated from fibrinogen  fibrin)</p><p> c.ii.1.a. Factor XIII (13) leads to fibrin polymers</p><p> c.ii.1.a.i. Fibrin polymers anchor the filaments</p><p>7. Understand and be able to describe the role of the Vitamin K in hemostasis.</p><p> a. Vit K is necessary for post-ribosomal CARBOXYLATION of the terminal glutamic acid residues of all Vit K dependent proteins</p><p> b. Vitamin K-Dependent Coagulation Proteins: (1972)</p><p> b.i. F X</p><p> b.ii. F IX</p><p> b.iii. F VII Normal Hemostasis: Objectives</p><p> b.iv. F II</p><p> c. Vitamin K-Dependent Anti-coagulation proteins:</p><p> c.i. Protein C and Protein S</p><p> c.i.1. Inactivate cofactors V and VIII </p><p> c.i.2. Prevent Clotting</p><p>8. Innumerate and describe the major mechanisms which regulate the hemostatic process including:</p><p> a. Antithrombin III: Do not affect factors V and VIII</p><p> a.i. Quick anti-clotting abilities to slow down all the clotting pathways</p><p> b. Protein C: Inactivates cofactors V and VIII to prevent clotting</p><p> c. Protein S: Inactivates cofactors V and VIII to prevent clotting</p><p> d. Plasminogen-Plasmin System: breaks down and inhibits fibrin polymerization</p><p> d.i. Products of split fibrin are anticoagulants</p><p> d.ii. Example is: t-PA</p>