1. Thrombosis Dr Aarathi Rau

2. Hemostasis Normal hemostasis: the end result of a set of well regulated processes that accomplish fluid blood in the normal blood vessel Rapid & localized hemostatic plug at the site of vessel injury.

3. Normal hemostasis Arteriolar constriction Exposure of extracellualar matrix (ECM) beneath the endothelium Adherence of platelets to form platelet plug Activation of platelets & degranulation (ADP,thrombin, thromboxane A2) Tissue factor (from injury) stimulate coagulation cascade Fibrin clot & platelets form secondary hemostatic plug Limit size of clot by fibrinolysis

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5. Thrombosis Definition: the pathological process characterized by intravascular clotting in a living person. Thrombus: intravascular clot Formed from the constituents of blood Occurs in an uninjured vessel or after relatively minor injury.

6. Virchows triad Endothelial injury Stasis or abnormal blood flow hypercoagulability

7. Endothelium PROTHROMBOTIC vWF---platelet adherence Thromboplastin PAF-----------fibrin formation inhibitors pf Plasminogen activator ( PA I)--- depresses fibrinolysis ANTITHROMBOTIC Antiplatelet: NO,PGI 2 – vasodilators block platelet adherence & aggregation Anti coagulant Thrombomodulin Antithrombin III-interferes with clotting Tissue type Plasminogen activator (t PA) promotes fibrin lysis

8. Causes of endothelial injury Hemodynaminc injury e.g. hypertension Atherosclerosis Inflammation (thrombophlebitis) Autoimmune diseases e.g.Polyarteritis nodosa (PAN) Metabolic:hyperlipidemia,homocystinemia Trauma Infections

9. Altered blood flow Turbulent flow (disruption of normal laminar flow)- arterial stasis (venous) Platelets & WBC’s in contact with endothelial cells

11. Effects of altered blood flow Activation of endothelial cells so that procoagulant > anticoagulant Prevent removal of platelets and Prevent fresh anticoagulants from blood reaching endothelium Stasis-dilated veins Mechanical damage of endothelium

12. Altered composition of blood Hypercoagulability Heriditary: deficiency of Protein C/S,Factor V Leiden,Antithrombin III (AT III) Hyperhomocystinemia (acquired or congential ) Acquired tissue damage -  thromboplastin Tumour, bacteria,smoking Autoimmune :SLE,PAN Antiphospholipid antibodies

14. Formation of a thrombus Virchows triad predisposes Platelets adhering to site of endothelial injury Fibrin RBC’s +Fibrin+Platelets Lines of Zahn Propogation

15. Morphology of thrombus Lines of Zahn platelets+ fibrin alternating with fibrin + RBC’s+ platelets Attached to vessel wall Friable along the lines of Zahn Moulded to blood vessel

17. Site of Thrombi Arterial -Coronary, cerebral, femoral Site of endothelial injury (AS), turbulence (bifurcation) Venous- Lower extremities(90%)-superficial /deep veins of legs Ovarian,periuterine,portal hepatic vein in sites of stasis

18. Site of Thrombi (cont.) Cardiac (usual mural) –ventricles: site of endothelial injury, MI, dilated cardiomyopathy –atria: occur in sites of stasis, Atrial Fibrillation Heart Valves (vegetations) –infective endocarditis –non-bacterial thrombotic endocarditis –Verrucous (Libman-Sacks )endocarditis

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23. Arterial Vs Venous thrombus Arterial –lines of Zahn more prominent paler in colour usually occlusive, retrograde propagation Venous –less prominent lines of Zahn red/ darker in colour(like clotted blood) Invariably occlusive, propagate in direction of blood flow/towards the heart Post mortem clot: not friable, not attached to blood vessel, currant jelly, chicken fat

24. Fate of /Outcome of thrombus Dissolution-fibrinolysis of RECENT thrombi Propagation-grow downstream Embolization-detach& travel elsewhere in circulation Organization-granulation tissue grows into the thrombus Recanalization-blood vessels fuse into larger channels allowing resumption of blood flow.

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26. Common causes of thrombosis T –Tissue damage H- Heriditary -deficiency of ProteinC/S, Factor V Leiden,Antithrombin III R- Rest O –Obstetric M- Malignancy (Trosseau syndrome ) B- Blood flow disturbances I- Immune mechanisms SLE,Antipholspolipid Ab, PAN

27. Clinical importance of thrombi Cause obstruction of arteries and veins Possible source of emboli

28. Clinical complications Arterial & cardiac thrombosis-Infarction, CAD Systemic Embolization Venous obstruction –Oedema,DVT Pulmonary Emboli Infection –secondary infection,mycotic aneurysm Inflammation of vessel wall –thrombophlebitis Trosseau syndrome-migratory thrombophlebitis associated with internal malignancy due to procoagulant substances.

29. MCQ’s In which of the following conditions are lines of Zahn seen? Post mortem clot Primary platelet clot Corraline thrombus Clot in sample bottle

30. In which of the following conditions are lines of Zahn seen? Post mortem clot Primary platelet clot Corraline thrombus √ Clot in sample bottle

31. Which is the earliest step in the formation of a thrombus? Formation of fibrin Adherence of platelets to vascular sub endothelium Activation of clotting factor VII Trapping of RBC’s

32. Which is the earliest step in the formation of a thrombus? Formation of fibrin Adherence of platelets to vascular sub endothelium √ Activation of clotting factor VII Trapping of RBC’s

33. SHORT ANSWER QUESTIONS Fate of a thrombus Virchows triad Predisposing factors for thrombosis Difference between post-mortem clot and thrombus

34. CLINICAL IMPORTANCE Major cause of morbidity and mortality