Vascular Disturbances II

Thrombosis and Embolism

2nd Year Pathology 2010

 Thromboembolic events
Activation of coagulation system Solid mass of
blood constituents formed within the vasculature
Thrombosis formation of blood clot at site of
coagulation system activation
Embolism migration through the vasculature to a
distant site
Cause tissue damage by occlusion of blood vessels
Result in ischaemia and infarction

2nd Year Pathology 2010

 Thromboembolic events
ischaemia
lack of oxygen due to impaired blood supply
results in reversible cell injury or irreversible injury and
necrosis (infarction)
depends on duration & tissues metabolic needs
infarction
tissue necrosis due to ischaemia
Major causes of morbidity & mortality
myocardial infarction, stroke, pulmonary embolism

2nd Year Pathology 2010

 Thrombosis
Inappropriate activation of haemostatic
mechanisms
E.g. uninjured vessel or very minor injury
Definition:
formation of solid mass of blood constituents within
vascular system in life
Virchows triad:
1. changes in the vessel wall
2. changes in blood flow
3. changes in the blood constituents

2nd Year Pathology 2010

 Changes in the vessel wall
Primarily damage to intimal surface (endothelium)
Causes of endothelial cell injury:
ulcerated atherosclerotic plaques
scarred valves in endocarditis / prosthetic valves
radiation, cigarette smoke, cholesterol/lipids
Results of endothelial cell injury:
exposed subendothelial extracellular matrix
platelet activation
activation of coagulation cascade
depletion of antiplatelet, anticoagulant and fibrinolytic functions
endothelial activation activation of procoagulant functions

2nd Year Pathology 2010

 Endothelium
Antithrombotic functions Procoagulant functions
Antiplatelet
Adenosine diphosphatase
( ADP)
Prostacyclin and nitric Production of vWF
oxide (also vasodilation) Production of tissue factor
Anticoagulant Binding of factors IXa and
Heparin-like molecules Xa
(activate antithrombin III)
Thrombomodulin
(activates protein C)
Protein S synthesis
Fibrinolytic
t-PA

2nd Year Pathology 2010

 Changes in blood flow
Normal flow is laminar
cells in centre of blood stream
clear zone of plasma adjacent to endothelium
Disrupted flow is static or turbulent
Stasis
Platelets in contact with endothelium
Prevent dilution of clotting factors
Retard inflow of clotting factor inhibitors
e.g. myocardial infarct, aneurysm, atrial fibrillation,
hyperviscosity syndromes
Turbulence
Eddy currents with local pockets of stasis
Promote endothelial cell injury
e.g. ulcerated atherosclerotic plaque
2nd Year Pathology 2010
 Changes in blood constituents
Hypercoagulability
Leads to recurrent venous thrombosis, arterial thrombosis,
recurrent abortion and stillbirths
Inherited (see table overleaf) or Acquired (below)
oral contraceptive use
pregnancy / hyperoestrogenic states
malignancy - elaboration of a procoagulant factor, leading to arterial
and venous thrombosis (Trousseaus syndrome)
tissue damage surgery, trauma, burns
Hyperviscosity
predisposes to stasis in small vessels
polycythaemia) / deformed RBCs (sickle cell anaemia)
Presence of endothelial cell toxins
toxins in cigarette smoke, high levels of lipid or cholesterol
predispose to endothelial cell injury
2nd Year Pathology 2010
 Anti-phospholipid autoantibodies bind plasma proteins with affinity for
syndrome phospholipid surfaces, including coagulation factors
associated with SLE
Factor V Leiden most common inherited form of hypercoagulability
mutation present in 5% of Caucasians
mutant factor V resistant to protein C inactivation
Elevated factor VIII as common as factor V Leiden mutation
genetic and environmental factors including OCP use
Protein C, Protein S, autosomal dominantly inherited deficiencies of
antithrombin III anticoagulant factors
deficiencies
Homocystinemia elevated plasma homocysteine levels
also increased rick of atherosclerosis
Prothrombin mutation increases the level and activity of prothrombin

Plasminogen Plasminogen or tissue plasminogen activator

abnormalities deficiency, plasminogen activator inhibitor excess
features resemble protein C or S deficiency
Sticky platelet autosomal dominant disorder, precipitated by stress
syndrome
2nd Year Pathology 2010
 Thrombus Formation
Atherosclerotic plaque
1. initial fatty streak
2. plaque enlarges (smoking/hyperlipidaemia)
3. turbulence (due to protrusion into lumen)
4. loss of endothelium & exposure of collagen
5. platelet adherence & activation
6. fibrin meshwork deposition with RBC entrapment
7. more turbulence, more platelet adherence, more fibrin
deposition
8. thrombus of alternating layers of platelets, fibrin and
red blood cells
2nd Year Pathology 2010
 Arterial Thrombi
Large vessels (aorta, heart) - nonocclusive / mural
Smaller vessels (coronary arteries, leg arteries) - often
occlusive
Classically have alternating white and red layers
called lines of Zahn
alternating layers of pale platelets and darker RBCs
e.g. aneurysmal sacs, infarcted left ventricle, damaged
heart valves, atherosclerotic plaques
Consequences:
Ischaemia in tissues distal to thrombus with possible necrosis
(infarction)
May embolize due to rapid flow

2nd Year Pathology 2010

 Arterial Thrombi

Non-occlusive thrombi in wall of atherosclerotic aorta

2nd Year Pathology 2010
 Arterial Thrombi

Occlusive thrombus in wall of atherosclerotic coronary artery

2nd Year Pathology 2010
 Arterial Thrombi

a b

Alternating layers of a) platelets and fibrin and b) red blood cells

2nd Year Pathology 2010
 Venous Thrombi
Sites of stasis, commonly veins of lower extremity
Red - More enmeshed erythrocytes, less platelets
Occlusive
Predisposing factors
Bed rest, immobilization, heart failure, surgery, trauma,
pregnancy, hypercoagulable states
Consequences:
Rarely cause ischaemia if affect arterial supply
More commonly embolize

2nd Year Pathology 2010

 Fate of Thrombi
1. Dissolution
by fibrinolysis
2. Propagation
along length of vessel complete vessel occlusion
3. Embolization
4. Recanalization
capillaries invade thrombus to re-establish blood flow
5. Organization
Inflammation and fibrosis replacement by scar, may obliterate
vessel lumen

Recent thrombi may be completely dissolved

Older thrombi more resistent to fibrinolysis
(extensive fibrin polymerization)
2nd Year Pathology 2010
 Consequences of Thrombosis
Arterial Thrombosis
Obstruction:
Myocardial infarction due to coronary artery thrombosis
Cerebral infarction (Stroke) due to carotid artery thrombosis
Acute lower limb ischaemia & infarction due to femoral/popliteal
artery thrombosis
Embolization:
Cardiac/aortic mural thrombi emboli to brain, kidneys, spleen
Venous Thrombosis e.g. deep leg veins
Obstruction:
Local congestion, swelling, pain, tenderness
Oedema and impaired venous drainage
Infection & varicose ulcers
Embolization
Thrombi at or above knee pulmonary emboli
2nd Year Pathology 2010
 Consequences of Thrombosis

Acute myocardial infarct secondary to coronary artery thrombosis

2nd Year Pathology 2010
 Embolism
Any intravascular mass (solid, liquid or gas)
carried by blood to site distant from point of origin
Most derived from thrombi (thromboembolism)
Lodge in vessels too small to permit further
passage
partial / complete vascular occlusion
distal tissue ischaemia & infarction

2nd Year Pathology 2010

 Pulmonary Thromboembolism
Arise from thrombi in systemic venous circulation
leg veins (95%)
pelvic veins
intracranial venous sinuses
Risk factors as for venous thrombosis
Effects are two-fold:
Possible infarction of lung tissue supplied by infarct
Interruption of oxygenation of blood within this area
Interruption of right ventricular outflow
Effects depend on size
2nd Year Pathology 2010
 Pulmonary Thromboembolism

Embolus migrates from deep leg veins through venous system to

2nd Year Pathology 2010
pulmonary circulation
 Pulmonary Thromboembolism
Small:
silent due to collateral bronchial artery flow
organization with cumulative damage (idiopathic
pulmonary hypertension)
Medium:
pulmonary infarct with acute respiratory and cardiac
symptoms
Large:
right heart failure & collapse (>60% pulm circ)
Massive:
sudden death e.g. saddle embolus
2nd Year Pathology 2010
 Systemic Thromboembolism
Arise in arterial system (heart/large arteries)
Atheromatous plaque with thrombus
Valve vegetation
Atrial thrombus (Atrial Fibrillation)
Old myocardial infarct (adynamic)
Recent myocardial infarct (loss of endothelium)

Rarely paradoxical embolus from venous system

(through septal defect in heart)

2nd Year Pathology 2010

 Systemic Thromboembolism
Travel in systemic circulation
Cause arterial occlusion, distal ischaemia &
infarction
brain - stroke, neurological deficit / death
renal/splenic infarcts may be asymptomatic, seen as
ischaemic scars at autopsy
intestine - mesenteric emboli cause intestinal infarction,
can be lethal
limbs - ischaemic foot (dry gangrene)

2nd Year Pathology 2010

 Other Forms of Embolism
Fat embolism
Next most common after thromoemboli
Fracture of long bones / Burns / Trauma
Can cause severe pulmonary insufficiency
Air embolism
Gas bubbles obstructing vascular flow
Surgical /obstetric procedures / Chest wall injury
Decompression sickness
Gases dissolve in blood at high pressure
Come out as bubbles during rapid decompression
N2 bubbles remain - muscle, jts, lungs, brain, heart

2nd Year Pathology 2010

 Other Forms of Embolism
Atheromatous plaque embolism
Platelet emboli
Infective emboli (infective endocarditis)
Tumour emboli
Foreign material (talc in IVDU)
Amniotic fluid embolism
amniotic fluid forced into uterine veins @ delivery,
causing respiratory distress

2nd Year Pathology 2010

 Summary
Thrombosis
Normal haemostatic mechanisms
Pathogenesis: Virchows triad
Arterial vs Venous Thrombi
Fate of Thrombi
Embolism
Types of embolus
Systemic vs Pulmonary Embolism
Other Causes of Vascular Insufficiency
Consequences of Vascular Insufficiency
2nd Year Pathology 2010