Leicester Warwick Medical School

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Leicester Warwick Medical School
Haemostasis Thrombosis and Embolism Dr. Kevin
West kpw2_at_le.ac.uk Department of Pathology
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Why dont you bleed to death from a minor injury?
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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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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.
• gt90 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 gt60 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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