Thrombosis and thromboembolism These slides were kindly provided by AstraZeneca

2. Thrombosis A thrombus is defined as a blood clot comprising platelets, blood cells, coagulation factors and fibrin which forms in the blood vessel and adheres to the vessel wall, frequently causing vascular obstruction. Thrombosis is the formation, development or presence of a thrombus and can occur as a natural wound-healing process, preventing excessive blood loss in response to vessel injury. However, it can also be initiated in the venous system, or become over-activated in the presence of risk factors, such as trauma and stasis during surgery, malignancy and immobilisation. In the arterial system thrombosis occurs in the presence of atherosclerosis. When thrombosis occurs inappropriately, it is a disease state.A thrombus is defined as a blood clot comprising platelets, blood cells, coagulation factors and fibrin which forms in the blood vessel and adheres to the vessel wall, frequently causing vascular obstruction. Thrombosis is the formation, development or presence of a thrombus and can occur as a natural wound-healing process, preventing excessive blood loss in response to vessel injury. However, it can also be initiated in the venous system, or become over-activated in the presence of risk factors, such as trauma and stasis during surgery, malignancy and immobilisation. In the arterial system thrombosis occurs in the presence of atherosclerosis. When thrombosis occurs inappropriately, it is a disease state.

3. Thromboembolism Thromboembolism involves part or all of the thrombus breaking away from the site of origin and being carried in the blood stream until lodged in a different vessel, too small to let it pass. The mass that breaks away from the thrombus and circulates in the blood stream is known as an embolus.Thromboembolism involves part or all of the thrombus breaking away from the site of origin and being carried in the blood stream until lodged in a different vessel, too small to let it pass. The mass that breaks away from the thrombus and circulates in the blood stream is known as an embolus.

4. Thrombi may form in veins, arteries and the heart Thrombi may form in any part of the cardiovascular system, including veins, arteries, the heart and microcirculation. Thrombi may form in any part of the cardiovascular system, including veins, arteries, the heart and microcirculation.

5. Venous thrombi The relative proportions of cells and fibrin are determined by haemodynamics, therefore arterial and venous thrombi differ in composition.The relative proportions of cells and fibrin are determined by haemodynamics, therefore arterial and venous thrombi differ in composition.

6. Arterial thrombi The relative proportions of cells and fibrin are determined by haemodynamics, therefore arterial and venous thrombi differ in composition.The relative proportions of cells and fibrin are determined by haemodynamics, therefore arterial and venous thrombi differ in composition.

7. Thrombosis and thromboembolism The consequences of arterial and venous thrombosis are also different as the thrombi and any resulting emboli occlude vessels and therefore blood flow to different regions of the body. Emboli become lodged in the first small vessels to which they are carried in the blood stream. Thus emboli originating in the venous system or in the right side of the heart commonly become lodged in the lungs, causing pulmonary embolism (PE), while emboli that originate in the large arteries of the left side of the heart frequently become lodged in vessels in the brain, causing stroke.The consequences of arterial and venous thrombosis are also different as the thrombi and any resulting emboli occlude vessels and therefore blood flow to different regions of the body. Emboli become lodged in the first small vessels to which they are carried in the blood stream. Thus emboli originating in the venous system or in the right side of the heart commonly become lodged in the lungs, causing pulmonary embolism (PE), while emboli that originate in the large arteries of the left side of the heart frequently become lodged in vessels in the brain, causing stroke.

8. Venous thromboembolism Venous thrombi originate in the muscular veins or the valve cusp pockets of the deep veins in the leg (deep vein thrombosis, DVT). The low blood flow or stasis favours the development of relatively long thrombi. Unlike the arterial system, the venous circulation of the legs contains extensive additional veins, so called collaterals, and the effects of venous thrombus are therefore less acute and may even go unnoticed.Venous thrombi originate in the muscular veins or the valve cusp pockets of the deep veins in the leg (deep vein thrombosis, DVT). The low blood flow or stasis favours the development of relatively long thrombi. Unlike the arterial system, the venous circulation of the legs contains extensive additional veins, so called collaterals, and the effects of venous thrombus are therefore less acute and may even go unnoticed.

9. Venous thromboembolism The end of the long thrombus in the deep veins �The end of the long thrombus in the deep veins �

10. Venous thromboembolism �embolises in the pulmonary circulation, which can lead to a life-threatening acute pulmonary embolism and/or the long-term condition pulmonary hypertension.�embolises in the pulmonary circulation, which can lead to a life-threatening acute pulmonary embolism and/or the long-term condition pulmonary hypertension.

11. Venous thromboembolism

12. Arterial thromboembolism Arterial thrombosis is most commonly triggered by the spontaneous or mechanical rupture of atherosclerotic plaques, which occurs in most major arteries including the aorta, carotid, iliofemoral and the coronary arteries.Arterial thrombosis is most commonly triggered by the spontaneous or mechanical rupture of atherosclerotic plaques, which occurs in most major arteries including the aorta, carotid, iliofemoral and the coronary arteries.

13. Arterial thromboembolism Arterial thrombosis is most commonly triggered by the spontaneous or mechanical rupture of atherosclerotic plaques, which occurs in most major arteries including the aorta, carotid, iliofemoral and the coronary arteries.Arterial thrombosis is most commonly triggered by the spontaneous or mechanical rupture of atherosclerotic plaques, which occurs in most major arteries including the aorta, carotid, iliofemoral and the coronary arteries.

14. Arterial thromboembolism The resulting thrombi extend into the lumen and the plaque, often becoming incorporated into the vessel wall where they can further accelerate the growth of the atherosclerotic plaque. As the thrombosis progresses, blood flow is reduced and wall shear is increased, promoting further platelet and fibrin disposition and therefore further growth of the thrombi. Growth of thrombi and/or atherosclerotic plaques often leads to complete occlusion of the vessel. In addition, emboli may form and become lodged downstream, occluding smaller vessels. Obstruction of blood flow results in tissue ischaemia in organs such as the heart, brain or in extremities. The three principal categories of diesase associated with arterial thrombosis are: coronary artery disease cerebrovascular disease peripheral arterial occlusive disease (PAOD).The resulting thrombi extend into the lumen and the plaque, often becoming incorporated into the vessel wall where they can further accelerate the growth of the atherosclerotic plaque. As the thrombosis progresses, blood flow is reduced and wall shear is increased, promoting further platelet and fibrin disposition and therefore further growth of the thrombi. Growth of thrombi and/or atherosclerotic plaques often leads to complete occlusion of the vessel. In addition, emboli may form and become lodged downstream, occluding smaller vessels. Obstruction of blood flow results in tissue ischaemia in organs such as the heart, brain or in extremities. The three principal categories of diesase associated with arterial thrombosis are: coronary artery disease cerebrovascular disease peripheral arterial occlusive disease (PAOD).

15. Arterial thromboembolism The resulting thrombi extend into the lumen and the plaque, often becoming incorporated into the vessel wall where they can further accelerate the growth of the atherosclerotic plaque. As the thrombosis progresses, blood flow is reduced and wall shear is increased, promoting further platelet and fibrin disposition and therefore further growth of the thrombi. Growth of thrombi and/or atherosclerotic plaques often leads to complete occlusion of the vessel. In addition, emboli may form and become lodged downstream, occluding smaller vessels. Obstruction of blood flow results in tissue ischaemia in organs such as the heart, brain or in extremities. The three principal categories of diesase associated with arterial thrombosis are: coronary artery disease cerebrovascular disease peripheral arterial occlusive disease (PAOD). The resulting thrombi extend into the lumen and the plaque, often becoming incorporated into the vessel wall where they can further accelerate the growth of the atherosclerotic plaque. As the thrombosis progresses, blood flow is reduced and wall shear is increased, promoting further platelet and fibrin disposition and therefore further growth of the thrombi. Growth of thrombi and/or atherosclerotic plaques often leads to complete occlusion of the vessel. In addition, emboli may form and become lodged downstream, occluding smaller vessels. Obstruction of blood flow results in tissue ischaemia in organs such as the heart, brain or in extremities. The three principal categories of diesase associated with arterial thrombosis are: coronary artery disease cerebrovascular disease peripheral arterial occlusive disease (PAOD).

16. Arterial thromboembolism The resulting thrombi extend into the lumen and the plaque, often becoming incorporated into the vessel wall where they can further accelerate the growth of the atherosclerotic plaque. As the thrombosis progresses, blood flow is reduced and wall shear is increased, promoting further platelet and fibrin disposition and therefore further growth of the thrombi. Growth of thrombi and/or atherosclerotic plaques often leads to complete occlusion of the vessel. In addition, emboli may form and become lodged downstream, occluding smaller vessels. Obstruction of blood flow results in tissue ischaemia in organs such as the heart, brain or in extremities. The three principal categories of diesase associated with arterial thrombosis are: coronary artery disease cerebrovascular disease peripheral arterial occlusive disease (PAOD). The resulting thrombi extend into the lumen and the plaque, often becoming incorporated into the vessel wall where they can further accelerate the growth of the atherosclerotic plaque. As the thrombosis progresses, blood flow is reduced and wall shear is increased, promoting further platelet and fibrin disposition and therefore further growth of the thrombi. Growth of thrombi and/or atherosclerotic plaques often leads to complete occlusion of the vessel. In addition, emboli may form and become lodged downstream, occluding smaller vessels. Obstruction of blood flow results in tissue ischaemia in organs such as the heart, brain or in extremities. The three principal categories of diesase associated with arterial thrombosis are: coronary artery disease cerebrovascular disease peripheral arterial occlusive disease (PAOD).

17. Arterial thromboembolism The resulting thrombi extend into the lumen and the plaque, often becoming incorporated into the vessel wall where they can further accelerate the growth of the atherosclerotic plaque. As the thrombosis progresses, blood flow is reduced and wall shear is increased, promoting further platelet and fibrin disposition and therefore further growth of the thrombi. Growth of thrombi and/or atherosclerotic plaques often leads to complete occlusion of the vessel. In addition, emboli may form and become lodged downstream, occluding smaller vessels. Obstruction of blood flow results in tissue ischaemia in organs such as the heart, brain or in extremities. The three principal categories of diesase associated with arterial thrombosis are: coronary artery disease cerebrovascular disease peripheral arterial occlusive disease (PAOD). The resulting thrombi extend into the lumen and the plaque, often becoming incorporated into the vessel wall where they can further accelerate the growth of the atherosclerotic plaque. As the thrombosis progresses, blood flow is reduced and wall shear is increased, promoting further platelet and fibrin disposition and therefore further growth of the thrombi. Growth of thrombi and/or atherosclerotic plaques often leads to complete occlusion of the vessel. In addition, emboli may form and become lodged downstream, occluding smaller vessels. Obstruction of blood flow results in tissue ischaemia in organs such as the heart, brain or in extremities. The three principal categories of diesase associated with arterial thrombosis are: coronary artery disease cerebrovascular disease peripheral arterial occlusive disease (PAOD).

18. Arterial thromboembolism The resulting thrombi extend into the lumen and the plaque, often becoming incorporated into the vessel wall where they can further accelerate the growth of the atherosclerotic plaque. As the thrombosis progresses, blood flow is reduced and wall shear is increased, promoting further platelet and fibrin disposition and therefore further growth of the thrombi. Growth of thrombi and/or atherosclerotic plaques often leads to complete occlusion of the vessel. In addition, emboli may form and become lodged downstream, occluding smaller vessels. Obstruction of blood flow results in tissue ischaemia in organs such as the heart, brain or in extremities. The three principal categories of diesase associated with arterial thrombosis are: coronary artery disease cerebrovascular disease peripheral arterial occlusive disease (PAOD). The resulting thrombi extend into the lumen and the plaque, often becoming incorporated into the vessel wall where they can further accelerate the growth of the atherosclerotic plaque. As the thrombosis progresses, blood flow is reduced and wall shear is increased, promoting further platelet and fibrin disposition and therefore further growth of the thrombi. Growth of thrombi and/or atherosclerotic plaques often leads to complete occlusion of the vessel. In addition, emboli may form and become lodged downstream, occluding smaller vessels. Obstruction of blood flow results in tissue ischaemia in organs such as the heart, brain or in extremities. The three principal categories of diesase associated with arterial thrombosis are: coronary artery disease cerebrovascular disease peripheral arterial occlusive disease (PAOD).

19. Arterial thromboembolism The resulting thrombi extend into the lumen and the plaque, often becoming incorporated into the vessel wall where they can further accelerate the growth of the atherosclerotic plaque. As the thrombosis progresses, blood flow is reduced and wall shear is increased, promoting further platelet and fibrin disposition and therefore further growth of the thrombi. Growth of thrombi and/or atherosclerotic plaques often leads to complete occlusion of the vessel. In addition, emboli may form and become lodged downstream, occluding smaller vessels. Obstruction of blood flow results in tissue ischaemia in organs such as the heart, brain or in extremities. The three principal categories of diesase associated with arterial thrombosis are: coronary artery disease cerebrovascular disease peripheral arterial occlusive disease (PAOD). The resulting thrombi extend into the lumen and the plaque, often becoming incorporated into the vessel wall where they can further accelerate the growth of the atherosclerotic plaque. As the thrombosis progresses, blood flow is reduced and wall shear is increased, promoting further platelet and fibrin disposition and therefore further growth of the thrombi. Growth of thrombi and/or atherosclerotic plaques often leads to complete occlusion of the vessel. In addition, emboli may form and become lodged downstream, occluding smaller vessels. Obstruction of blood flow results in tissue ischaemia in organs such as the heart, brain or in extremities. The three principal categories of diesase associated with arterial thrombosis are: coronary artery disease cerebrovascular disease peripheral arterial occlusive disease (PAOD).

20. Intracardiac thrombosis Intracardiac thrombi commonly develop in the left atrial appendage due to atrial fibrillation, on inflamed, damaged or prosthetic valves, on endocardium adjacent to a region of myocardial infarction and in a dilated or dyskinetic (irregularly contracting) chamber. Activation of the coagulation cascade is the principal mechanism in the pathogenesis of intracardiac thrombi, but platelet activation also plays a significant role.Intracardiac thrombi commonly develop in the left atrial appendage due to atrial fibrillation, on inflamed, damaged or prosthetic valves, on endocardium adjacent to a region of myocardial infarction and in a dilated or dyskinetic (irregularly contracting) chamber. Activation of the coagulation cascade is the principal mechanism in the pathogenesis of intracardiac thrombi, but platelet activation also plays a significant role.

21. Intracardiac thrombosis Generaly, thrombi are asymptomatic when confined to the heart, but complications arise when part of the thrombus embolises to the cerebral or systemic circulation. Atrial fibrillation results in abnormal blood flow and stasis in the atria, condintions that predispose to thrombi generation in the left atrial appendage. Embolisation to the cerebral circulation and subsequent stroke is a recognised life-threatening complication of atrial fibrillation. Generaly, thrombi are asymptomatic when confined to the heart, but complications arise when part of the thrombus embolises to the cerebral or systemic circulation. Atrial fibrillation results in abnormal blood flow and stasis in the atria, condintions that predispose to thrombi generation in the left atrial appendage. Embolisation to the cerebral circulation and subsequent stroke is a recognised life-threatening complication of atrial fibrillation.