Hemostasis in Pathology
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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.
Hemostasis in Pathology
- 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 hemostasisBlood vessels- vasoconstrictionPlateletsCoagulationFibrinolytic systemInhibitor of coagulation
- 3. Blood vesselsEndothelial vessels activateCoagulation cascadeFibrinolytic systemsProtein C systemsvWF
- 4. Properties of blood vesselsProthrombotic prop.vWFTissue factor –factor 3 + thromboplastinFibrinolysis inhibitor- PAIs
- 5. Antithrombotic prop.Antiplatelet effect- prostacyclins, nitric oxideAnticoagulant effect –thrombomodulinThrombomodulin inactivates thrombin to make it an anticoagulant!Fibrinolysis properties- t-PAClear fibrin deposits from endothelial surfaces.
- 6. Role of plateletsPlatelet adhere to exposed subendotheliat collagenAdhered platelet undergo release reaction resulting in formation of aggregation.1. adhesion-vWF- glycoprotein Ib assoc.2. secretion/release- Ca2+ , ADP, thromboxane A23.aggregation-glycoprotein 2b- 3a receptorsConformational changes of GP2b-3a allows platelet to bind fibrinogens.
- 7. 2 pathways of coagulationIntrinsicExtrinsic*final common pathway=Prothrombin thrombin
- 8. Assessment of the pathwaysPT(prothrombin time)- extrinsic pathwayFactor 7, 10, 2, 5PTT(partial thromboplastin time-intrinsic pathwayFactor 12, 11, 9, 8, 10, 5, 2 + fibrinogen
- 9. Control of coagulationAntithrombinprotein C and SFibrinolytic cascadePlasminogenplasmin FSP (fibrin split products)D-dimer is the most important FSP
- 10. Summary of hemostasisPrimary hemostasisBV constrictionPlatelet plug formationSecondary hemostasisActivation of clotting cascadeDeposition &stabilisation of fibrin
- 11. Tertiary hemostasisDissolution of fibrin clotRemoval of fibrin plug
- 12. Bleeding disordersVascular abnormalitiesPlatelet disordersCF (clotting factor) disordersDIC (disseminated intravascular coagulation)
- 13. Vascular abnormalitiesInfectionEg: meningococcemia,rickettsiosses, infective endocarditisDrug reactionHereditary hemorrhagic telangiectesiaAutosomal dominant inheritanceCushing syndromeHeroch-scholeinpurpuraSystemic hypersensitivity disease of unknown causePolyarthralgia and acute glomerulonephritisPalpable purpuric rash, coliclyabdomnal pain=treated with steroids
- 14. ITP
- 15. ITP (idipathicthrombocutopenicpurpura)Autoimmune disorder accelerated destruction of sensitized platelets by phagocytic cells in the RES.*very2 important
- 16. Clasification of ITPChildren / adult onsetAcute / chronicPrimary / secondary (idiopathic)
- 17. Acute-children (post-infection)Chronic-adult (> female, 20-40 yrs. Old)Autoimmune disordersAntiplateletAb (IgG)IgG coated platelets removed by spleen> megakaryocytes in bone marrow*blood picture !!! Very important.
- 18. Characteristic of ITPSudden onset of bruising / petechiaeCase history of infectious diseaseAppear respiratory tract infection in about 3 weeks prior to onset of bleedingDangerous-intracerebellar hemorrhage<20,000 platelet count.
- 19. ITP bone marrow aspirate
- 20. Additional infost-PA most important plasminogen. plasminogen is activated by streptokinase.To prevent excessive thrombi destruction, free plasminogen quickly bind to α2-antiplasmin.
- 21. PAIsEndothelial 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.