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Leicester Warwick Medical School Haemostasis Thrombosis and Embolism Dr. Kevin West Department of Pathology.

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Presentation on theme: "Leicester Warwick Medical School Haemostasis Thrombosis and Embolism Dr. Kevin West Department of Pathology."— Presentation transcript:

1 Leicester Warwick Medical School 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 A 2 cause platelet aggregation 5HT, platelet factor 3 also released PF3 important in coagulation Platelets coalesce after aggregation

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

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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

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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

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

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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 –ischaemia –infarction –depends on site and collateral circulation Venous –congestion –oedema –ischaemia –infarction

32 Coronary artery thrombosis

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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

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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

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