Leicester Warwick Medical School

Haemostasis Thrombosis
and Embolism
Dr. Kevin West
kpw2@le.ac.uk
Department of Pathology
 Why don’t you bleed to
death from a minor injury?
 Objectives 1

• Haemostasis
 Objectives 2

• Thrombosis
– definition
– predisposing factors
– effects
– outcomes
– common clinical examples
 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
 Haemostasis

Successful haemostasis depends on

• vessel wall
• platelets
• coagulation system
• fibrinolytic system
 Blood Vessels

• constrict to limit blood loss

• arteries, veins, capillaries
• mechanism not fully understood
 Platelets

• adhere to damaged vessel wall

• adhere to each other
• form a platelet plug
• platelet release reaction
 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
 Coagulation

• Cascade
• Series of inactive components
converted to active components
• Prothrombin Thrombin

Fibrinogen Fibrin
 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
 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

 Fibrinolysis

• Breakdown of fibrin
• Plasminogen Plasmin

Plasminogen activators

• Fibrinolytic therapy widely used

– streptokinase
– tPA
 Endothelium

• Anti-thrombotic
– plasminogen activators
– prostacyclin
– nitric oxide
– thrombomodulin
 Thrombosis

• Definition

Thrombosis is the formation of a solid

mass of blood within the circulatory
system
 Why does thrombosis occur?

• Abnormalities of the vessel wall

– atheroma
– direct injury
– inflammation
 Why does thrombosis occur?

• Abnormalities of blood flow

– stagnation
– turbulence
• Abnormalities of blood components
– smokers
– post-partum
– post-op
 Appearances of thrombi

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

• Venous
– soft
– gelatinous
– deep red
– higher cell content
 Outcomes of thrombosis

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

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

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

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

• Embolism
– part of thrombus breaks off
– travels through bloodstream
– lodges at distant site
 Effects of thrombosis

• Arterial • Venous
– ischaemia – congestion
– infarction – oedema
– depends on site and – ischaemia
collateral circulation – infarction
Coronary artery thrombosis
Coronary artery thrombosis
 Rudolf Virchow

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

 Embolism

• Other types
– air
– amniotic fluid
– nitrogen
– medical equipment
– tumour cells
 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
 Deep vein thrombosis

• predisposing factors
– immobility/bed rest
– post-operative
– pregnancy and post-
partum
– oral contraceptives
– severe burns
– cardiac failure
– disseminated cancer
 Can DVT be prevented?

• high risk patients must be identified and

offered prophylaxis
– heparin sub-cutaneously
– leg compression during surgery
 Can DVT be treated?

• intravenous heparin
• oral warfarin
 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
Pulmonary embolism