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HEMOSTASIS & THROMBOSIS pathology mobs 2nd year
- 1. Hemostasis and Thrombosis 1 Dr. RakeshKumar Gupta, M.D. Asst. Professor Dept of Pathology
- 2. Normal hemostasis isthe result of a set of well- regulated processes that accomplish two important functions: (1)They maintain blood in a fluid, clot-free state in normal vessels; and (2)They are poised to induce a rapid and localized hemostatic plug at a site of vascular injury. 2
- 3. NORMAL HEMOSTASIS 3 The generalsequence of events in hemostasis at the site of vascular injury • Brief arteriolar vasoconstriction, reflex neurogenic and local secretion like endothelin • Primary hemostasis: Exposure of subendothelial ECM platelets to adhere > activated > release secretory granules >aggregation > Hemostatic plug • Secondary hemostasis: Tissue factor + secreted platelet factors > activate coagulation cascade > activation of thrombin> fibrin clot, further platelet recruitment and granule release • Activation of counterregulatory mechanisms, t-PA are set
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- 5. Endothelium Antithrombotic Properties: Antiplatelet,anticoagulant & fibrinolytic effects Prothrombotic Properties: vWF, TNF, IL1, Antifibrinolytic effects 5
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- 8. The fibrinolytic system 8 Thefibrinolytic system, illustrating the plasminogen activators and inhibitors
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- 10. Definition • Thrombus –a blood clot • Thrombosis – a pathological process whereby there is formation of a blood clot in uninjured vasculature or after relatively minor injury 10
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- 12. Dr. Rudolph Virchow 1821-1902 Abnormal BloodFlow Abnormal Vessel Wall Abnormal Blood The Hypercoagulable State •Primary (genetic) •Secondary (acquired) Virchow’s 12
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- 14. Endothelial Injury 14 • Dominantfactor • Sufficient as the sole factor • Examples include – Myocardial infarction – Ulcerated atheromatous plaques – Hemodynamic injury such as hypertension, turbulent flow over heart valves – Endotoxins, inflammation, etc
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- 22. Thrombosis Venous Deep Vein Thrombosis PulmonaryEmbolism Arterial Myocardial Infarction Stroke 22
- 23. Multigenic + Environmental Factors Genetic Associationsand Hemostasis Genetic diagnosis available Genetic therapy feasible Genetic pathogenesis still under investigation Hemophilia Thrombosis Single Gene Mutation Single Gene Disorder 23
- 24. XII XIIa XI XIa IXIXa X Xa II IIa Fibrinogen Fibrin VIIIa+Ca+Pl Va+Ca+Pl TF / VIIa TFPI IIa/Thrombomodulin interaction Protein C Protein S Protein S Fibrinolysis 24
- 25. Loss of FunctionMutations Natural Anticoagulant Proteins Antithrombin Protein C Protein S 0.02 – 0.2% of General Population 1-3% prevalence in Thrombosis Population 25
- 26. Acquired/Environmental Thrombotic Factors 26 Immobility– Blood stasis Surgery Cancer Pregnancy Oral Contracep tion
- 27. Abnormal Blood Flow 27 •Turbulence in arterial flow as a result of changes in the diameter of the vessel leading to non-laminar flow, resulting in: Platelet coming into contact with endothelium. Prevent dilution by fresh flowing blood of activated clotting factors. Retard inflow of clotting factor inhibitors. Promote endothelial cell activation predisposing to local thrombosis.
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- 29. Hypercoagulabili ty 29 • Alteration ofthe coagulation pathway that predisposes to thrombosis • Higher viscosity of blood changing the flow dynamics of blood
- 30. Primary (Genetic) Common Mutation infactor V gene (factor V Leiden) Mutation in prothrombin gene Mutation in methyltetrahydrofolate gene Rare Antithrombin III deficiency Protein C deficiency Protein S deficiency Very rare Fibrinolysis defects 30 Secondary (Acquired) High risk for thrombosis Prolonged bed rest or immobilization Myocardial infarction Atrial fibrillation Tissue damage (surgery, fracture, burns) Cancer Prosthetic cardiac valves Disseminated intravascular coagulation Heparin-induced thrombocytopenia Antiphospholipid antibody syndrome (lupus anticoagulant syndrome) Lower risk for thrombosis Cardiomyopathy Nephrotic syndrome Hyperestrogenic states (pregnancy) Oral contraceptive
- 31. Morphology of thrombus • Thrombimay develop anywhere in the cardiovascular system: within the cardiac chambers; on valve cusps; or in arteries, veins, or capillaries. • They are of variable size and shape • Arterial or cardiac thrombi usually begin at a site of endothelial injury (e.g., atherosclerotic plaque) or turbulence (vessel bifurcation) • Venous thrombi characteristically occur in sites of stasis. • Characteristic of all thromboses – firmly attached at the point of origin • Growth of thrombi: Arterial thrombi – grow in a retrograde direction Venous thrombi - grow in the direction of blood flow • Complication: Embolus. 31
- 32. • Lines ofZahn • Mural thrombi • Arterial thrombi • Venous thrombosis, or phlebothrombosis • Vegetations 32
- 33. Aortic aneurysm withthrombus formation – note the Lines of Zahn 33
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- 36. Vegetations in Infectiveendocarditis involving the aortic valve 36
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- 38. Arterial 38 Venous Usually Occlusive Alwaysocclusive Occlusion of vascular lumen Endothelial injury Present May be absent Firmly adherent Loosely adherent Adhesion to vessel wall Colour Grey white red Consistency Friable Firm Site Coronary, cerebral, femoral Lower limbs, dural sinuses, portal vein
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- 40. Venous thrombi VsPM clots 40 • Postmortem clots are gelatinous • A dark red dependent portion where red cells have settled by gravity and a yellow chicken fat supernatant resembling melted and clotted chicken fat; • They are usually not attached to the underlying wall • In contrast, red thrombi are firmer, almost always have a point of attachment, and on transection reveal vague strands of pale gray fibrin.
- 41. Venous thrombus 41 PM clot Not adherent Adhesionto vessel wall Colour Red / yellow layers Consistency Adherent at one point Red with pale grey fibrin lines on c/s Firm Gelatinous Site Lower limbs, dural sinuses, portal vein Any where in the body Venous thrombi Vs PM clots
- 42. Fate of aThrombus 42 Four events in the ensuing days to weeks: • The thrombus may propagate • The thrombus may become organised and recanalised • The thrombus may become organised and incorporated into the wall of the vessel • The thrombus may be dissolved completely • The thrombus may dislodge and become an embolus or emboli
- 43. Fate of aThrombus 43
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- 48. Classification of Thrombi 48 •Anatomical – Cardiac – Arterial – Venous – Capillary • Morphological – Pale (platelet thrombus) – Red (RBC thrombus) – Mixed (intermittent layers)
- 49. Thrombosis of the descendingaorta extending from the origins of the renal arteries down to the iliac vessels Renal Artery Thrombus 49 Iliac Artery
- 50. A mixed thrombus Redthrombus Pale thrombus 50
- 51. Venous Thrombosis 51 • Twodistinct types – Phlebothrombosis – predisposes to thromboemboli to lungs – Thrombophlebitis – unusual to have associated pulmonary thromboemboli Migratory thrombophlebitis or Trousseau syndrome
- 52. DISSEMINATED INTRAVASCULAR COAGULATION (DIC) 52 DICis not a primary disease but rather a potential complication of any condition associated with widespread activation of thrombin It’s a thrombohemorrhagic disorder Thrombin formation is the main mechanism Both platelets and coagulation factors are depleted Lab findings: Low PLT count, >aPTT, >PT, fragmented RBCs in the smear
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- 55. Effects of Thrombosis 55 •Dependent on location and degree of vascular occlusion. • Effects also dependent on the availability of collateral blood supply and susceptibility of area of supply to interruption of blood supply.
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