Thrombosis

Thrombosis is the inappropriate

activation of clotting occurring in
uninjured or minimally injured vessels.
There are 3 primary influences on the
propensity towards thrombosis
(Virchow’s Triad):
Endothelial injury
Alteration in flow
Hypercoagulability

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 Endothelial injury
This is the dominant influence
Thrombosis results from exposed ECM and tissue factor and platelet adhesion

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 Alteration of Flow
Normal blood flow is laminar with cellular elements located
centrally in the vessel lumen separated from the endothelial wall by
a plasma clear zone. Stasis and turbulent flow disrupt laminar flow
with a number of consequences:
platelets contact endothelium
Stasis elicits thrombosis in the venous system, cardiac chambers
and aneurysmal dilatations.
Plaques disrupt laminar flow in addition to producing endothelial
injury.
Anything that promotes blood viscosity (hyperviscosity syndromes)
promotes stasis (polycythemia, sickle cell, dehydration, etc.).

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 Hypercoagulability
An alteration of coagulation that predisposes to thrombosis, this is the least frequent
cause for thrombosis but allows the simplest opportunity for intervention.

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 Hypercoagulability
Acquired Hypercoagulability:
1. Oral contraceptives or hyper-estrogenic states (pregnancy) create
hypercoagulability by increasing the synthesis of coagulation factors and
deceased production of antithrombin III.
2. Certain malignancies and disseminated cancers release procoagulant tumor
products.
3. Advanced age is associated with increased platelet aggregation.
4. Smoking

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 Morphology of Thrombi
Thrombi may form any where in the vascular
system, they vary in size and shape depending
on their site of origin and how firmly they are
attached at their origin.
Arterial thrombi Click to edit Master text styles
Found in areas of active flow
Second level
● Third level
Commonly show layering of platelets & fibrin (Lines of ● Fourth level
Zahn)
● Fifth level
Cardiac & aortic thrombi tend to be non-occlusive
(↑↑↑flow).
Tend to propagate distally often with embolization (can
propagate retrograde)
Atherosclerotic plaques, endothelial injury, areas of
turbulent flow serve as nidus

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 Venous thrombosis:
1. Characteristically in areas of low/no flow or turbulent flow.
2. Superficial thrombi usually occur in enlarged saphenous veins.
3. Deep vein thrombi (DVT) generally occur in veins proximal to the knee and due to
the abundant collateral venous system are asymptomatic in 50 % of instances prior
to an embolic event. The situations associated with increased risk of DVT are legion,
anything that involves prolonged immobilization (? > 8 hours, particularly associated
with dehydration) CHF, trauma (including surgical), pregnancy and post-partum
states* and malignancy.
4. Often associated with inflammatory changes ( thrombophlebitis).

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 The Fate of the Thrombus
Once formed the thrombus has a limited number of fates:
1. Propagation with subsequent vessel occlusion, depending
on the location and type of vessels the sequelae may be
minor (superficial vein thrombosis) or catastrophic (stroke,
MI, etc.).
2. Embolization to downstream sites (PE)
3. Dissolution by fibrinolytic activity (a therapeutic intervention)
4. Organization & recanalization, endothelial cells, smooth
muscle cells and fibroblasts create vascular channels in the
thombus.

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 Embolism

Embolism refers to any intravascular

mass carried by blood flow to a site
distant from its origin, most arise from
thrombi;
other emboli may consist of fat, gas
bubbles, atherosclerotic debris**,
tumor fragments, bone marrow,
foreign bodies, particulate matter, etc.
Emboli lodge in vessels too small to
permit further passage, the distribution
depending on blood flow drown-
stream from the source.

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 Pulmonary Thromboembolism
PE has a reported incidence of 20-25/100,000
hospitalized patients, >95% of PEs originate
from DVTs. Increased risk with immobilization,
post-op and CHF (venous stasis).
Most PEs (60-80%) are clinically silent.
Obstruction of medium sized pulmonary arteries
may cause pulmonary hemorrhage but
pulmonary infarction is ~rare due to the
bronchial blood supply.
Obstructon of ≥60% of the pulmonary circulation
results in right-heart failure, cardiovascular
collapse or sudden death. (Saddle embolus).
Multiple emboli over time may result in
pulmonary hypertension.

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 Systemic Thromboembolism
Systemic emboli most often arise from intracardiac mural thrombi, often
associated with MI. 25% arise from dilated LA due to valvular disease.
Atherosclerotic plaques are frequently the source of non-cardiac emboli.
The consequences of arterial occlusion depends on collateral circulation and
tissue sensitivity to hypoxia.

Click to edit Master text styles

Second level
● Third level

● Fourth level

● Fifth level

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Common sites of arrest
ICA branches, especially the MCA
Mesenteric artery branches
Renal artery branches (however ~75%
loss of renal function before symptomatic)
Paradoxical emboli
Click to edit Master text styles
Intracardiac (R→L) shunt (patent foramen
ovale or ASD) of emboli can occur Second level
particularly with equalization of pressures ● Third level

(↑ right side with pulmonary hypertension, ● Fourth level

↓ left side CHF, MI, etc.).
● Fifth level

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 Air Embolism
Gas bubbles in the vasculature can cause
obstruction resulting in ischemia, room air may
enter the circulation any time large low pressure
venous structures are disrupted (thoracic, pelvic,
obstetric, lower extremity, neck and spine
procedures), approximately 100 mls of air is
required to be symptomatic.

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 Conclusions
1. Thrombosis is the inappropriate activation of hemostasis
2. Vircow’s triad describes the predisposing factors for thrombosis
1. Endothelial injury/activation
2. Alteration in flow
3. Hypercoaguability
3. Normal endothelial function is a delicate balance between pro- and anti-thrombotic influences,
normally anti-thrombosis predominates.
4. Abnormal flow results in:
1. Stasis
2. Loss of dilution of activated factors
3. Loss of the influx of clot inhibitors
4. Promoting endothelial activation
5. Atherosclerotic plaques elicit
1. Abnormal flow patterns
2. Direct endothelial injury

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 Conclusions
6. Hypercoagulability
Inherited
Acquired
7. Hyperestrogenic states, malignancy, age, smoking, heparin induced,
thrombocytopenia, MI, A-fib, prosthetic valves, etc.
8. Thrombi may propagate, embolize, dissolve, organize and recanalize.
9. Venous thromboembolism
DVT-50% are asymptomatic prior to an embolic event
10. Arterial thrombosis
Often results in obstruction with ischemia unless a collateral circulatory system is readily available
Embolization to distal vasculature
12. DIC causes widespread microthrombi but presents as a bleeding diathesis due to
systemic activation of the fibrinolytic system

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 Conclusions
13.Anything reaching the intravascular system can embolize
Fat
Air
Amniotic fluid
14. PE
~1/2 -3/4ths are silent
Can cause acute right heart failure and death
15. Fat embolism is common (~90%) is severe skeletal trauma,
usually is asymptomatic but can present as acute pulmonary
failure, thrombocytopenia and CNS deterioation 1-3 days post
trauma.
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