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