Normal hemostasis

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Normal hemostasis

  1. 1. Normal Hemostasis Maintenance of fluidity of blood while in vessel and formation ofhemostatic plug on vascular injury
  2. 2. • Steps in hemostasis: 1.Vasoconstriction due to local neural response, and release of endothelin from the endothelium 2.Primary hemostatic plug: due to platelet adhesion, activation, degranulation(ADP, TXA2) and recruitment of other platelets 3.Secondary hemostasis due to activation of coagulation cascade by tissue factor and phospholipid via extrinsic pathway- the end result being fibrin which traps the cells in the blood forming a clot 4.Counter regulation: a.t-PA which activates plasmin( fibrinolytic cascade) b.PAI: plasminogen activator inhibitor c.Antithrombin III, protein c, protein S, thrombomodulin, PGI2, nitric oxide and ADPase
  3. 3. Anti-coagulant effects• HEPARIN-like molecules expressed on endothelial membrane – cofactors for antithrombin III to inactivate thrombin and other factors like IXa and Xa• Thrombomodulin expressed on endothelial surface binds thromin and the complex• Activates protein C which in presence of protein S breaks Va and VIIIa• Tissue factor pathway inhibitor• Fibrinolytic effects - t-PA synthesized by endothelial cells promote fibrinolytic activity to clear fibrin deposits from endothelial surfaces
  4. 4. • Once activated the coagulation cascade must be restricted to the local site of vascular injury to prevent clotting of the entire vascular tree.• Regulated by three types of natural anticoagulants•• Anti thrombin III• Protein C and Protein S• TFPI•• With onset of coagulation cascade, fibrinolytic cascade is also activated to limit the the size of final clot• Primarily accomplished by plasmin

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