Thrombosis

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

4. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM) © 2005 Elsevier

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. 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 Endothelium

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

20. Mural Thrombi Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM) © 2005 Elsevier

23. Arterial Vs Venous thrombus • Arterial –lines of Zahn more prominent paler in colour usually occlusive, retrogradepropagation • 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.

25. Potential Outcomes Of Venous Thrombosis Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM) © 2005 Elsevier

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