1. Leicester Warwick Medical School Department of Pathology
Haemostasis Thrombosis and Embolism
Dr. Kevin West
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. Appearances of thrombi
Venous
soft
gelatinous
deep red
higher cell content

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

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
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