Leicester Warwick Medical School

1. Leicester Warwick Medical School Haemostasis Thrombosis and Embolism Dr. Kevin West kpw2@le.ac.uk Department of Pathology

2. Why don’t you bleed to death from a minor injury?

3. Objectives 1 • Haemostasis

4. Objectives 2 • Thrombosis • definition • predisposing factors • effects • outcomes • common clinical examples

5. Objectives 3 • Embolism • definition • thromboembolism • other types of embolism • pathogenesis of DVT and pulmonary embolism • pathophysiology of pulmonary embolism • prevention and treatment of thrombo-embolic disease

6. Haemostasis Successful haemostasis depends on • vessel wall • platelets • coagulation system • fibrinolytic system

7. Blood Vessels • constrict to limit blood loss • arteries, veins, capillaries • mechanism not fully understood

8. Platelets • adhere to damaged vessel wall • adhere to each other • form a platelet plug • platelet release reaction

9. Platelet Release Reaction • ATP ADP • ADP, thromboxane A2 cause platelet aggregation • 5HT, platelet factor 3 also released • PF3 important in coagulation • Platelets coalesce after aggregation

12. Coagulation • Cascade • Series of inactive components converted to active components • Prothrombin Thrombin Fibrinogen Fibrin

14. Coagulation • 1 ml of blood can generate enough thrombin to convert all the fibrinogen in the body to fibrin • Tight regulation therefore required • Balance of procoagulant and anticoagulant forces

15. Control of Coagulation • Thrombin destroys factors V and VIII • Thrombin inhibitors • anti-thrombin III* • alpha 1 anti-trypsin • alpha 2 macroglobulin • protein C and S* * inherited deficiency may thrombosis

16. Fibrinolysis • Breakdown of fibrin • Plasminogen Plasmin Plasminogen activators • Fibrinolytic therapy widely used • streptokinase • tPA

17. Endothelium • Anti-thrombotic • plasminogen activators • prostacyclin • nitric oxide • thrombomodulin

18. Thrombosis • Definition Thrombosis is the formation of a solid mass of blood within the circulatory system

19. Why does thrombosis occur? • Abnormalities of the vessel wall • atheroma • direct injury • inflammation

20. Why does thrombosis occur? • Abnormalities of blood flow • stagnation • turbulence • Abnormalities of blood components • smokers • post-partum • post-op

22. Appearances of thrombi • Arterial • pale • granular • lines of Zahn • lower cell content

23. Appearances of thrombi

24. Venous soft gelatinous deep red higher cell content Appearances of thrombi

25. Outcomes of thrombosis • Lysis • complete dissolution of thrombus • fibrinolytic system active • bloodflow re-established • most likely when thrombi are small

26. Outcomes of thrombosis • Propagation • progressive spread of thrombosis • distally in arteries • proximally in veins

28. Outcomes of thrombosis • Organisation • reparative process • ingrowth of fibroblasts and capillaries (similar to granulation tissue) • lumen remains obstructed

29. Outcomes of thrombosis • Recanalisation • bloodflow re-established but usually incompletely • one or more channels formed through organising thrombus

30. Outcomes of thrombosis • Embolism • part of thrombus breaks off • travels through bloodstream • lodges at distant site

31. Arterial ischaemia infarction depends on site and collateral circulation Venous congestion oedema ischaemia infarction Effects of thrombosis

32. Coronary artery thrombosis

33. Coronary artery thrombosis

34. Rudolf Virchow • b. Pomerania 1821 • graduated in medicine 1843 • presented work on thrombosis 1845 but could not get it published • founded own journal

35. Rudolf Virchow • 1848 studied typhus epidemic in Prussia • Attributed typhus to poor social conditions which upset the government • Became a political activist and was sacked in 1849 after building barricades in Berlin uprising

36. Rudolf Virchow • Appointed Professor of Pathology in Wurzburg • Described leukaemia, pulmonary embolism and much more • 1856 appointed Professor of Pathology in Berlin despite government opposition

37. Rudolf Virchow • 1858 published ‘Cellular Pathology’ one of the most influential medical books ever written • 1880-93 Member of Reichstag • Died aged 81 after fracturing his hip jumping from a moving tram

38. Embolism • Definition Embolism is the blockage of a blood vessel by solid, liquid or gas at a site distant from its origin. >90% of emboli are thrombo-emboli

39. Embolism • Other types • air • amniotic fluid • nitrogen • medical equipment • tumour cells

40. Thrombo-emboli • from systemic veins pass to the lungs = pulmonary emboli • from the heart pass via the aorta to renal, mesenteric, and other femoral arteries • from atheromatous carotid arteries pass to the brain • from atheromatous abdominal aorta pass to arteries of the legs

42. Deep vein thrombosis • predisposing factors • immobility/bed rest • post-operative • pregnancy and post-partum • oral contraceptives • severe burns • cardiac failure • disseminated cancer

43. Can DVT be prevented? • high risk patients must be identified and offered prophylaxis • heparin sub-cutaneously • leg compression during surgery

44. Can DVT be treated? • intravenous heparin • oral warfarin

45. Pulmonary embolism - effects • massive PE >60% reduction in bloodflow rapidly fatal • major PE - medium sized vessels blocked. Patients short of breath +/- cough and blood stained sputum • minor PE - small peripheral pulmonary arteries blocked. Asymptomatic or minor shortness of breath • recurrent minor PEs lead to pulmonary hypertension

46. Pulmonary embolism