Leicester Warwick Medical School Haemostasis Thrombosis and Embolism Dr. Kevin West [email protected]...
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Transcript of Leicester Warwick Medical School Haemostasis Thrombosis and Embolism Dr. Kevin West [email protected]...
![Page 1: Leicester Warwick Medical School Haemostasis Thrombosis and Embolism Dr. Kevin West kpw2@le.ac.uk Department of Pathology.](https://reader033.fdocuments.net/reader033/viewer/2022050920/551ba22455034669548b46a7/html5/thumbnails/1.jpg)
Leicester Warwick Medical School
Haemostasis Thrombosis and Embolism
Dr. Kevin [email protected]
Department of Pathology
![Page 2: Leicester Warwick Medical School Haemostasis Thrombosis and Embolism Dr. Kevin West kpw2@le.ac.uk Department of Pathology.](https://reader033.fdocuments.net/reader033/viewer/2022050920/551ba22455034669548b46a7/html5/thumbnails/2.jpg)
Why don’t you bleed to death from a minor injury?
![Page 3: Leicester Warwick Medical School Haemostasis Thrombosis and Embolism Dr. Kevin West kpw2@le.ac.uk Department of Pathology.](https://reader033.fdocuments.net/reader033/viewer/2022050920/551ba22455034669548b46a7/html5/thumbnails/3.jpg)
Objectives 1
• Haemostasis
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Objectives 2
• Thrombosis– definition– predisposing factors– effects – outcomes – common clinical examples
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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
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Haemostasis
Successful haemostasis depends on
• vessel wall
• platelets
• coagulation system
• fibrinolytic system
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Blood Vessels
• constrict to limit blood loss
• arteries, veins, capillaries
• mechanism not fully understood
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Platelets
• adhere to damaged vessel wall
• adhere to each other
• form a platelet plug
• platelet release reaction
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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
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Coagulation
• Cascade
• Series of inactive components converted to active components
• Prothrombin Thrombin
Fibrinogen Fibrin
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![Page 14: Leicester Warwick Medical School Haemostasis Thrombosis and Embolism Dr. Kevin West kpw2@le.ac.uk Department of Pathology.](https://reader033.fdocuments.net/reader033/viewer/2022050920/551ba22455034669548b46a7/html5/thumbnails/14.jpg)
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
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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
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Fibrinolysis
• Breakdown of fibrin• Plasminogen Plasmin
Plasminogen activators
• Fibrinolytic therapy widely used– streptokinase– tPA
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Endothelium
• Anti-thrombotic– plasminogen activators– prostacyclin– nitric oxide– thrombomodulin
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Thrombosis
• Definition
Thrombosis is the formation of a solid mass of blood within the circulatory system
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Why does thrombosis occur?
• Abnormalities of the vessel wall– atheroma– direct injury– inflammation
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Why does thrombosis occur?
• Abnormalities of blood flow– stagnation– turbulence
• Abnormalities of blood components– smokers– post-partum– post-op
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Appearances of thrombi
• Arterial– pale– granular– lines of Zahn– lower cell content
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Appearances of thrombi
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Appearances of thrombi
• Venous– soft– gelatinous– deep red– higher cell content
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Outcomes of thrombosis
• Lysis– complete dissolution of thrombus– fibrinolytic system active– bloodflow re-established– most likely when thrombi are small
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Outcomes of thrombosis
• Propagation– progressive spread
of thrombosis– distally in arteries– proximally in veins
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Outcomes of thrombosis
• Organisation– reparative process– ingrowth of
fibroblasts and capillaries (similar to granulation tissue)
– lumen remains obstructed
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Outcomes of thrombosis
• Recanalisation– bloodflow re-
established but usually incompletely
– one or more channels formed through organising thrombus
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Outcomes of thrombosis
• Embolism– part of thrombus breaks off– travels through bloodstream– lodges at distant site
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Effects of thrombosis
• Arterial– ischaemia– infarction– depends on site and
collateral circulation
• Venous– congestion– oedema– ischaemia– infarction
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Coronary artery thrombosis
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Coronary artery thrombosis
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Rudolf Virchow
• b. Pomerania 1821• graduated in
medicine 1843• presented work on
thrombosis 1845 but could not get it published
• founded own journal
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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
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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
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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
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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
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Embolism
• Other types– air– amniotic fluid– nitrogen– medical equipment– tumour cells
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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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Deep vein thrombosis
• predisposing factors– immobility/bed rest– post-operative– pregnancy and post-
partum– oral contraceptives– severe burns – cardiac failure– disseminated cancer
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Can DVT be prevented?
• high risk patients must be identified and offered prophylaxis– heparin sub-cutaneously– leg compression during surgery
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Can DVT be treated?
• intravenous heparin
• oral warfarin
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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
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Pulmonary embolism
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