Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

4 hemostasis&thrombosis

2,233 views

Published on

for Undergraduate medical students (MBBS)

Published in: Health & Medicine
  • Be the first to comment

4 hemostasis&thrombosis

  1. 1. Hemostasis and ThrombosisHemostasis and Thrombosis Dr.CSBR.Prasad, M.D.
  2. 2. Normal hemostasis is the 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.
  3. 3. NORMAL HEMOSTASISNORMAL HEMOSTASIS The general sequence of events in hemostasis at the site of vascular injury • There is a brief period of arteriolar vasoconstriction, reflex neurogenic mechanisms and local secretion of factors such as endothelin • Primary hemostasis: Exposure of subendothelial extracellular matrix (ECM) platelets to adhere > activated > release secretory granules > aggregation > Hemostatic plug • Secondary hemostasis: Tissue factor + secreted platelet factors > activate the coagulation cascade > activation of thrombin fibrin clot, resulting in local fibrin deposition. further platelet recruitment and granule release • Activation of counterregulatory mechanisms, t-PA are set into motion to limit the hemostatic plug to the site of injury
  4. 4. Diagrammatic representation of the normal hemostatic process: A, transient vasoconstriction: B, Platelets adhere to exposed extracellular matrix (ECM) via von Willebrand factor (vWF) and are activated, undergoing a shape change and granule release; released adenosine diphosphate (ADP) and thromboxane A2 (TxA2) lead to further platelet aggregation to form the primary hemostatic plug. C, Local activation of the coagulation cascade (involving tissue factor and platelet phospholipids) results in fibrin polymerization, "cementing" the platelets into a definitive secondary hemostatic plug. D, Counter-regulatory mechanisms, such as release of tissue type plasminogen activator (t-PA) (fibrinolytic) and thrombomodulin (interfering with the coagulation cascade), limit the hemostatic process to the site of injury.
  5. 5. EndotheliumEndothelium Antithrombotic Properties: Antiplatelet, anticoagulant & fibrinolytic effects Prothrombotic Properties: vWF, TNF, IL1, Antifibrinolytic effects
  6. 6. PlateletsPlatelets
  7. 7. CoagulationCoagulation cascadecascade
  8. 8. The fibrinolytic system The fibrinolytic system, illustrating the plasminogen activators and inhibitors
  9. 9. ThrombosisThrombosis
  10. 10. Components of Blood • Plasma – proteins, electrolytes and water • Cells – RBCs, WBCs & PLTs
  11. 11. 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.
  12. 12. Procoagulant Factors Anticoagulant Factors The Hemostatic Balance
  13. 13. Definition • Embolus – A detached intravascular solid, liquid or gaseous mass that is carried by the blood to a site distant from its point of origin.
  14. 14. Dr. Rudolph Virchow 1821-1902 Abnormal Blood Flow Abnormal Vessel Wall Abnormal Blood The Hypercoagulable State •Primary (genetic) •Secondary (acquired) Virchow’s triad
  15. 15. ENDOTHELIAL INJURY ABNORMAL BLOOD FLOW HYPERCOAGULABILITY THROMBOSIS
  16. 16. Endothelial InjuryEndothelial Injury • Dominant factor • 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
  17. 17. Atherosclerosis involving aorta Normal aorta for comparison
  18. 18. Arterial Thrombosis
  19. 19. Polyarteritis nodosa (PAN)
  20. 20. Polyarteritis nodosa (PAN)
  21. 21. Giant cell arteritis
  22. 22. Thrombosis Venous Deep Vein Thrombosis Pulmonary Embolism Arterial Myocardial Infarction Stroke
  23. 23. Hemophilia Single Gene Mutation Thrombosis Multigenic + Environmental Factors Genetic Associations and Hemostasis Genetic diagnosis available Genetic therapy feasible Genetic pathogenesis still under investigation Single Gene Disorder
  24. 24. XII XIIa XI XIa IX IXa 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
  25. 25. Loss of Function Mutations Natural Anticoagulant Proteins Antithrombin Protein C Protein S 0.02 – 0.2% of General Population 1-3% prevalence in Thrombosis Population Stronger Risk Factors For VTE ~ 10 to 25-fold
  26. 26. Acquired/Environmental Thrombotic Factors Immobility – Blood stasis Surgery Cancer Pregnancy Oral Contraception Hormone Replacement Therapy
  27. 27. Abnormal Blood FlowAbnormal Blood Flow • 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.
  28. 28. Hypercoagulability • Alteration of the coagulation pathway that predisposes to thrombosis • Higher viscosity of blood changing the flow dynamics of blood
  29. 29. Primary (Genetic) Common Mutation in factor 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 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 use Sickle cell anemia Smoking
  30. 30. Morphology of thrombusMorphology of thrombus • Thrombi may 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. 31. • Lines of Zahn • Mural thrombi • Arterial thrombi • Venous thrombosis, or phlebothrombosis • Vegetations
  32. 32. Aortic aneurysm with thrombus formation – note the Lines of Zahn
  33. 33. “Lines of Zahn"
  34. 34. Vegetations in Infective endocarditis involving the aortic valve
  35. 35. Infected prosthetic valve with vegetations
  36. 36. Libman-Sacks endocarditis
  37. 37. ArterialArterial VenousVenous Occlusion of vascular lumen Usually Occlusive Always occlusive Endothelial injury Present May be absent Adhesion to vessel wall Firmly adherent Loosely adherent Colour Grey white red Consistency Friable Firm Site Coronary, cerebral, femoral Lower limbs, dural sinuses, portal vein
  38. 38. Venous thrombiVenous thrombi VsVs PM clotsPM clots • 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.
  39. 39. VenousVenous thrombusthrombus PM clotPM clot Adhesion to vessel wall Adherent at one point Not adherent Colour Red with pale grey fibrin lines on c/s Red / yellow layers Consistency Firm Gelatinous Site Lower limbs, dural sinuses, portal vein Any where in the body Venous thrombiVenous thrombi VsVs PM clotsPM clots
  40. 40. Fate of a ThrombusFate of a Thrombus 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
  41. 41. Fate of a ThrombusFate of a Thrombus
  42. 42. Propagation of Thrombus
  43. 43. Cerebral Embolism Formation
  44. 44. Classification of ThrombiClassification of Thrombi • Anatomical – Cardiac – Arterial – Venous – Capillary • Morphological – Pale (platelet thrombus) – Red (RBC thrombus) – Mixed (intermittent layers)
  45. 45. Thrombosis of the descending aorta extending from the origins of the renal arteries down to the iliac vessels Renal Artery Iliac Artery Thrombus
  46. 46. A mixed thrombus Red thrombus Pale thrombus
  47. 47. Venous ThrombosisVenous Thrombosis • Two distinct types – Phlebothrombosis – predisposes to thromboemboli to lungs – Thrombophlebitis – unusual to have associated pulmonary thromboemboli Migratory thrombophlebitis or Trousseau syndrome
  48. 48. DISSEMINATED INTRAVASCULARDISSEMINATED INTRAVASCULAR COAGULATION (DIC)COAGULATION (DIC) DIC is 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
  49. 49. Effects of ThrombosisEffects of Thrombosis • 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.
  50. 50. E N D

×