Thrombosis

Reference: Robbin's Basic Pathology 10th edition

1. thrombosis Mehak Naz B.S Radiology Submitted to : Mr. Abdul Wahid

2. outlines Introduction Morphology Pathogenesis Fate of Thrombus Treatment

3. introduction Thrombosis The formation or presence of a blood clot in a blood vessel is called Thrombosis . I t is normal for the body to produce clotting factors like platelets and fibrin when a blood vessel is injured, to prevent an excessive loss of blood from the body. If this effect is over productive it can obstruct the flow of blood and form an embolus that moves around the blood stream . Thrombus A thrombus is a blood clot that forms in a vessel and remains there.

4. thrombus Development of Thrombus Thrombi may develop anywhere in the cardiovascular system Within the cardiac chambers On valve cusps Or in vessels i.e. arteries veins or capillaries. Arterial or cardiac thrombi typically arise at the sites of endothelial injury(e.g. atherosclerotic plaque) or turbulence (e.g. bifurcation of vessels) Venous thrombi occurs at the site of stasis.

5. thrombus Size and Shape They are of variable size and shape Characteristic All thrombi are firmly attached at the point of origin. Growth of Thrombi Arterial thrombi Grow in retrograde direction Venous thrombi Extends in the direction of blood flow

6. thrombus Complication Embolus Thrombi are focally attached to the underlying vascular surface and tend to propagate toward the heart. The propagating portion of thrombus tends to be poorly attached and therefore prone to fragmentation and migration through the blood as embolus.

7. Morphology Lines of Zahn Mural thrombi Arterial thrombi Venous thrombi Postmortem clots Vegetation

8. Lines of zahn Grossly and microscopically apparent laminations of thrombi called Lines Of Zahn These represent pale platelet and fibrin layers alternating with darker red cell rich layers. Signify that thrombus is formed in flowing blood Presence can distinguish ante mortem thrombosis from the bland nonlaminated clots.

9. Mural thrombi Occurs in heart chambers or in the aortic lumen Precursors of Cardiac Mural Thrombi Abnormal myocardial contraction Arrhythmias Dilated cardiomyopathy Myocardial infarction Endomyocardial injury Myocarditis Catheter trauma Precursors of Aortic Thrombosis Atherosclerotic plaque Aneurismal dilation

10. Mural thrombi

11. Arterial thrombi Also known as cardiac thrombi Frequently occlusive Superimposed on an atherosclerotic plaque or other forms of vascular injury( vasculitis, trauma). Usually begins at sites of turbulence or endothelial injury Composed of meshwork of platelets, fibrin, red cells and degenerating leukocytes. Common sites of frequency: Coronary>cerebral>femoral arteries

12. Venous thrombi Also known as phlebothrombosis Usually occurs at sites of stasis Extends in direction of blood flow almost invariably occlusive These are formed in the sluggish venous circulation ,they tend to contain more enmeshed RBCs leading to the moniker red or stasis thrombi. Venous thrombi may not be well attached and are prone to detachment, creating emboli. The veins of lower extremities are most commonly affected.(90% of venous thrombosis)

13. Postmortem clots They have two portions Dependent portion gelatinous with dark red dependent portion where red cells are settled, Upper portion yellow chicken fat upper portion Usually not attached to underlying wall

14. Vegetation Thrombi on heart valves are called vegetation Causes Infective endocarditis Can be either due to blood borne bacteria or fungi adhering to previously damaged valves or can directly cause valve damage. Sterile vegetation also can develop on non infected valves in hyper coagulable states –non bacterial thrombotic endocarditis Libman sacks endocarditis sterile verrucuous endocarditis occurring in systemic lupus erythematosus.

15. Thrombosis in vessels Features Arterial thrombosis Venous thrombosis Sites Turbulence or endothelial injury Stasis Occlusive Frequently Almost always Appearance (+) lines of Zahn More enmeshed RBC’s and platelets Common sites of involvement Coronary>cerebral>femoral artery Lower extremity veins 90%

16. Pathogenesis of thrombus The primary abnormalities that lead to intravascular thrombosis are Endothelial injury Stasis or turbulent blood flow Hypercoagulability of the blood These three causes are referred as Virchow's triad.

17. Endothelial injury Most important factor in arterial thrombosis Includes thrombus formation in heart and arterial circulation , where the high rates of blood flow impede clot formation. Severe endothelial injury may triggers thrombosis by exposing Von Willebrand factor and tissue factor. Inflammation and other noxious stimuli also promote thrombosis by shifting the pattern of gene expression in endothelium to one that is prothrombic This change is sometimes refers to as endothelial activation or dysfunction.

18. Endothelial injury major prothrombic changes

19. Endothelial injury Examples include Myocardial infarction Hemodynamic injury such as hypertension turbulent flow over heart valves Endotoxins, inflammation Hyper cholestrolemia etc

20. Abnormal blood flow Turbulence or chaotic blood flow contributes to arterial and cardiac thrombosis by causing endothelial injury or dysfunction. Stasis is the major factor in development of venous thrombi. Normal blood flow is laminar Platelets are found mainly in the center of vessel lumen Separated from the endothelium by a slower moving layer of plasma. By contrast, in stasis and turbulence; Promote endothelial cells activation Disrupt laminar flow Slows washout of activated clotting factors Impedes the inflow of clotting factors inhibitors.

21. Abnormal blood flow Clinical manifestations include aneurysm- aortic and arterial dilation Acute myocardial infarction Rheumatic mitral valve stenosis - results in left arterial dilation Hyper viscosity syndromes such as polycythemia Vera – increase resistance to flow and cause small vessels stasis Sickle cell anemia – causes vascular occlusions

22. Hyper coagulability H ypercoagulability refers to an abnormally high tendency of the blood to clot, and is typically caused by alterations in coagulation factors. Contributes infrequently to arterial or intracardiac thrombosis but an important underlying risk factor for venous thrombosis alteration of the coagulation pathways are divided into two categories Primary genetic disorders Secondary acquired disorders.

23. Hypercoagulability causes

24. Hyper coagulability Primary genetic disorders Factor V mutation Prothrombin mutation Secondary acquired disorders Heparin induced thrombocytopenia syndrome Anti phospholipids antibody syndrome

25. Fate of thrombus If a patient survives an initial thrombotic event, during the ensuring days to weeks the thrombus evolves through some combination of the following four processes Propagation Accumulate more platelets and fibrin thus result to vessel obstruction Embolization Dislodgement and travel to other location Dissolution Result of fibrinolysis Organization and recanalization By ingrowth of endothelial cells ,smooth muscles and fibroblasts ; reestablishment of continuity of original lumen. Older thrombi have extensive fibrin polymerization and tend to become organized.

26. Treatment of thrombosis Thrombosis is most commonly treated with anticoagulants. These drugs don’t breakup existing blood clots from getting bigger and reduce your risk of developing more clots Blood thinners may be taken orally or given by IV or injected subcutaneously. Some examples of these drugs are; Warfarine and vitamin K antagonists can be taken orally Heparin by IV Streptokinase can be administered IV in emergency condition like heart attack. Ultrasound-accelerated thrombolysis can also be used.

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