PSL301H Lecture 5: Hemostasis 2025 (PDF)

PSL301H Lecture 5: Hemostasis Learning objectives Describe the three phases of hemostasis Write out all three pathways in the coagulation cascade Explain how anticoagulants act Predict the effect of an excess or inadequate levels of clotting factors on the coagulation pathways Understa...

PSL301H Lecture 5: Hemostasis Learning objectives Describe the three phases of hemostasis Write out all three pathways in the coagulation cascade Explain how anticoagulants act Predict the effect of an excess or inadequate levels of clotting factors on the coagulation pathways Understand some of the clinical relevance of coagulation Recall: Hematopoiesis  Platelets are needed for blood clotting Half-life of platelets = 10 days Thrombopoietin increases platelet numbers  Three phases of hemostasis 3. Coagulation phase 1. Vascular phase 2. Platelet phase  1) Vascular phase Neurogenic and myogenic control Vasoconstriction prolonged by: Serotonin Endothelin-1 Thromoboxane A2 2. Platelet phase Exposed collagen - Binds & activates platelets Factors released from platelet Factors attract more platelets Platelets aggregate; form plug  Platelet phase details Exposed collagen via vonWillebrand - Binds & activates factor platelets Factors released e.g. ADP, platelet from platelet activating factor (PAF), serotonin, Factors attract more platelets thromboxane A2 Platelets aggregate; form plug von Willebrand factor made by endothelial cells and platelets. Binds to both collagen and platelets. ADP PAF Platelet Serotonin aggregation Vasoconstriction Thromboxane A2 Platelet activation Note: Without injury platelets are NOT activated Prostacyclin (prostaglandin I2, PGI2) and nitric oxide (NO) - prevent platelet adhesion and are vasodilators 3. Coagulation cascade  Common pathway details Inactive plasma clotting factors (white boxes) converted to active enzymes.  Extrinsic pathway von Willebrand factor regulates levels of VIII Vitamin K needed for the synthesis of thrombin, VII, IX and X Anticoagulant called Coumadin (Warfarin) – blocks the action of Vitamin K Instrinsic pathway Summary But problems with this model e.g. Individuals with factor IX or factor VIII deficiency have severe bleeding even though their extrinsic and common pathways are normal and should be sufficient to promote clotting Newer model: Cell-based theory of coagulation  Cell-based: Initiation phase Cell membrane of smooth muscle cells or fibroblasts in sub-endothelial layer Exposure of tissue factor (TF) starts this phase produces small amount of thrombin https://cmijournal.files.wordpress.com/2016/04/53-58-cell-based-model.pdf  Amplification phase Thrombin activates factors V, XI, and VIII on surface of platelets https://cmijournal.files.wordpress.com/2016/04/53-58-cell-based-model.pdf  Propagation phase Active factors on the surface of platelets form tenase and then prothrombinase results in LARGE amounts of thrombin = thrombin burst Thrombin cleaves fibrinogen and factor XIII to result in fibrin formation and crosslinking https://cmijournal.files.wordpress.com/2016/04/53-58-cell-based-model.pdf How is the clot removed after healing has taken place? tPA released slowly by damaged endothelium  Physiological anticoagulants Name Released from Activated Function by Plasminogen/ Liver tPA and Breaksdown fibrin plasmin thrombin Tissue Many tissues Normally Activates plasminogen present plasminogen activator (tPA) Antithrombin III Liver Heparin Blocks IX, X, XI, XII, thrombin Prostacyclin Endothelial N/A Inhibits platelet cells aggregation Summary The three phases of hemostasis are the vascular, platelet and coagulation phases The three pathways in the coagulation cascade are the common, extrinsic and intrinsic pathways The cell-based theory of coagulation involves the initiation, amplification and propagation phases Anticoagulants act by causing the production of plasmin, blocking the action of thrombin or by inhibiting the synthesis of blood clotting factors. Understand some of the clinical relevance of coagulation