Normal hemostasis involves three key steps: vessel constriction and formation of a platelet plug to stop bleeding (primary hemostasis), activation of the clotting cascade and deposition of fibrin to stabilize the platelet plug (secondary hemostasis), and dissolution of the fibrin clot and removal of the plug (tertiary hemostasis). Bleeding disorders can result from abnormalities in blood vessels, platelets, or clotting factors. Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder where autoantibodies cause accelerated platelet destruction, which can lead to dangerous bleeding especially intracerebral hemorrhage when platelet counts fall below 20,000.
1. What is normal hemostasis? Normal hemostasis- process by which bleeding at any site arrested by the formation of a hemostatic plug. 1. Followed by removal of plug so that normal flow of blood through vessels is maintained.
2. Components of hemostasis Blood vessels- vasoconstriction Platelets Coagulation Fibrinolytic system Inhibitor of coagulation
3. Blood vessels Endothelial vessels activate Coagulation cascade Fibrinolytic systems Protein C systems vWF
4. Properties of blood vessels Prothrombotic prop. vWF Tissue factor –factor 3 + thromboplastin Fibrinolysis inhibitor- PAIs
5. Antithrombotic prop. Antiplatelet effect- prostacyclins, nitric oxide Anticoagulant effect –thrombomodulin Thrombomodulin inactivates thrombin to make it an anticoagulant! Fibrinolysis properties- t-PA Clear fibrin deposits from endothelial surfaces.
6. Role of platelets Platelet adhere to exposed subendotheliat collagen Adhered platelet undergo release reaction resulting in formation of aggregation. 1. adhesion-vWF- glycoprotein Ib assoc. 2. secretion/release- Ca2+ , ADP, thromboxane A2 3.aggregation-glycoprotein 2b- 3a receptors Conformational changes of GP2b-3a allows platelet to bind fibrinogens.
7. 2 pathways of coagulation Intrinsic Extrinsic *final common pathway= Prothrombin thrombin
9. Control of coagulation Antithrombin protein C and S Fibrinolytic cascade Plasminogenplasmin FSP (fibrin split products) D-dimer is the most important FSP
10. Summary of hemostasis Primary hemostasis BV constriction Platelet plug formation Secondary hemostasis Activation of clotting cascade Deposition &stabilisation of fibrin
16. Clasification of ITP Children / adult onset Acute / chronic Primary / secondary (idiopathic)
17. Acute-children (post-infection) Chronic-adult (> female, 20-40 yrs. Old) Autoimmune disorders AntiplateletAb (IgG) IgG coated platelets removed by spleen > megakaryocytes in bone marrow *blood picture !!! Very important.
18. Characteristic of ITP Sudden onset of bruising / petechiae Case history of infectious disease Appear respiratory tract infection in about 3 weeks prior to onset of bleeding Dangerous-intracerebellar hemorrhage <20,000 platelet count.
20. Additional infos t-PA most important plasminogen. plasminogen is activated by streptokinase. To prevent excessive thrombi destruction, free plasminogen quickly bind to α2-antiplasmin.
21. PAIs Endothelial cells regulate anticoagulation balance by secreting PAIs. (plasminogen activation inhibitor) PAI-block fibrinolysis, procoagulationefct. increased by certain cytokines. role in I.V thrombosis accompanying severe inflammation.