Thrombosis and Embolism

Question 1

What is a thrombus?

Answer 1

A thrombus is a solid mass formed from the constituents of the blood within the heart or vessels during life.

Question 2

What is thrombosis? When does it occur?

Answer 2

Thrombosis is the process of formation of a thrombus. It occurs when normal haemostatic mechanisms are turned on inappropriately.

Question 3

What is Virchow’s triad?

Answer 3

Virchow was the first to call the process thrombosis and he stated that it depended on three things (the triad of Virchow):
● Changes in the vascular wall (endothelial damage)
● Changes in blood flow (slow or turbulent flow)
● Changes in the blood (hyper coagulability)
It seems that two of three from the triad are enough to produce a thrombus, e.g., stasis and hyper coagulability without endothelial damage will result in a thrombus.

Question 4

Where do arterial thrombi usually occur?

Answer 4

Arterial and cardiac thrombi usually occur at a site of endothelial injury or turbulence.

Question 5

Where do venous thrombi usually occur?

Answer 5

Venous thrombi are often seen where there is stasis

Question 6

Why is there an increased risk of thrombi in the lower limbs during pregnancy?

Answer 6

Stasis and hypercoagulability are present in pregnancy when there is stasis due to pressure on the large veins of the pelvis by the gravid uterus and the blood is hypercoagulable. Consequently there is an increased risk of thrombi in the lower limbs in pregnancy.

Question 7

Why might endothelial damage occur?

Answer 7

This can occur in a number of situations including:

• after myocardial infarction (there is damage to area of endothelium overlying the infarct),
• secondary to the haemodynamic stress of hypertension, - on scarred heart valves,
• after trauma or surgery,
• in inflammation
• on the surface of atherosclerotic plaques when they break open.

Question 8

How does endothelial damage lead to thrombus formation?

Answer 8

When there is endothelial damage, platelets adhere to exposed von Willebrand factor/factor VIII
complex. When blood flow is swift, for example in arteries, the platelet thrombi generally don’t grow because the current washes away the platelets, chemical mediators and clotting factors. However if there is also stasis then a thrombus will form.

Question 9

How does abnormal blood flow lead to thrombus formation?

Answer 9

Abnormal blood flow gives platelets a better chance to stick to the endothelium and clotting factors a chance to accumulate.

Question 10

What are the causes of blood hypercoagubility?

Answer 10

• In pregnancy and after surgery, fractures or burns there are increased circulating levels of fibrinogen and factor VIII meaning that the blood is hypercoagulable.
• Smoking also results in hypercoagulability as it is known to activate Hageman factor (factor XII).
• Some cancers produce procoagulant substances.
• The oral contraceptive pill, particularly older preparations, causes hypercoagulability.
• Hypercoagulability is also seen in DIC.
• Hypercoagulability can be the result of inherited disorders such as factor V Leiden, antithrombin III deficiency, protein C deficiency or protein S deficiency.

Question 11

What are platelets?

Answer 11

Platelets are the smallest formed elements in the blood and because of this they are more concentrated along the endothelium. The platelets are therefore more likely to catch in an eddy behind a valve. Here they can form an aggregate and settle on the wall of the vessel, particularly if there is any endothelial injury or the blood flow is slow. Further platelets will join the aggregate. In some situations, for example after surgery, platelets aggregate more easily and the platelet collection will grow more quickly.

Question 12

What are lines of Zahn?

Answer 12

A thrombus is a laminated structure. The laminations are visible to the naked eye and are called lines of Zahn. They are more obvious in arterial thrombi, as opposed to venous thrombi, as blood flows over the surface of the forming thrombus in arteries.

Question 13

How do post-mortem clots differ from regular thrombi?

Answer 13

Post-mortem clots which form when blood is not flowing are not laminated. They are also more rubbery and shiny than pre-mortem thrombi and are not attached to the intima.

Question 14

What is thrombophlebitis?

Answer 14

Pain is not always present when a thrombus forms, although it often is when thrombi form in superficial veins. Thrombophlebitis refers to such painful superficial thrombi which, as the name implies, have associated inflammation in the wall of the vein

Question 15

What are parietal thrombi?

Answer 15

Thrombi are parietal when they are attached to the wall of the vessel and restrict the lumen

Question 16

What are occlusive thrombi?

Answer 16

Occlusive when they fill and obstruct the lumen.

Question 17

What causes occlusive thrombi to form in an artery?

Answer 17

Arterial thrombi tend to remain parietal. When occlusive thrombi do form in an artery it tends to be over an atherosclerotic plaque that has cracked open. Such thrombi in coronary arteries can be no bigger than a match head but can be fatal.

Question 18

What is a vegetation?

Answer 18

A thrombus on a cardiac valve is called a vegetation. They can be 2-3 cm long and they easily embolise. They usually form on the valves of the left heart as they are exposed to greater pressures and therefore microtrauma which exposes the thrombogenic subendothelial tissue. They can become infected and this is particularly common in intravenous drug abusers.

Question 19

What are the outcomes of thrombi?

Answer 19

Outcomes of Thrombi
A number of outcomes are possible:
● Resolution – the thrombus is dissolved
● Propagation – the thrombus grows
● Organisation – the thrombus undergoes fibrous repair and forms a fibrous scar on the wall of the vessel
● Recanalisation –new channels lined with endothelium run through the occlusion and restore blood flow.
● Embolisation – a part of the thrombus breaks off and embolises.

Question 20

What is recanalisation?

Answer 20

Of an occluding thrombus, new channels lined with endothelium run through the occlusion and restore blood flow, although the new channels may have significantly smaller capacity than the original vessel

Question 21

What is embolisation?

Answer 21

A part of the thrombus breaks off and embolises. This is called thromboembolism and is discussed below. Thrombi that form in the large veins of the lower limbs such as the femoral, iliac and popliteal veins are particularly
dangerous sources of thromboemboli.

Question 22

What are the clinical effects of thrombosis?

Answer 22

The most common clinical effects of thrombosis include:
● Occlusion of an artery at the site of the thrombus resulting in ischaemia and infarction, e.g., myocardial infarction.
● Embolisation of part of the thrombus resulting in occlusion of an artery distant to the site of the thrombus, e.g., pulmonary embolism, cerebrovascular accident.
● Congestion and oedema in the venous bed resulting in pain and sometimes skin ulceration.
● Repeated miscarriages due to thrombosis of the uteroplacental vasculature which is often seen in inherited thrombophilias.

Question 23

What is an embolus?

Answer 23

An embolus is a solid, liquid or gas that is carried by the blood and is large enough to become impacted in a vascular lumen

Question 24

What is embolism?

Answer 24

Embolism is the impaction of an embolus. A good
definition for embolism would be ‘Sudden blocking of an artery by a thrombus or foreign material which has been brought to its site of lodgement by the blood current’.

Question 25

What are thromboemboli?

Answer 25

Thromboemboli are emboli that arise from thrombi. They are far and away the most common type of emboli and when they occur are often multiple.

Question 26

Other than thromboemboli, what are the other types of emboli?

Answer 26

Emboli can also be composed of body fat, bone marrow, material from atheromatous plaques, tumour fragments, parasites, bubbles of air or other gases, debris injected intravenously, amniotic fluid, medical equipment or bits of brain or liver after trauma.

Question 27

Why doesn’t embolisation occur in veins?

Answer 27

In veins blood flow is from smaller to larger vessels, hence embolization cannot occur in veins. Objects carried by the blood in veins will therefore go through the right heart and embolise in the pulmonary arteries.

Question 28

Where do emboli occur in the arteries?

Answer 28

In arteries blood flow is from large to small arteries so
that objects carried by the blood in large arteries will become impacted into smaller arteries. Emboli from the left heart or aorta end up anywhere in the systemic circulation but especially in the lower limbs. Approximately 80% of pulmonary emboli arise from thrombi in the deep veins of the thigh and the popliteal vein (rather than the smaller veins of the calf)

Question 29

What are the clinical consequences of small pulmonary emboli?

Answer 29

Most pulmonary emboli are small and are clinically silent. However, multiple small pulmonary emboli can cause
pulmonary hypertension.

Question 30

What are the clinical consequences of large pulmonary emboli?

Answer 30

Large pulmonary emboli, resulting in more than 60% occlusion of the pulmonary circulation will cause sudden death, cor pulmonale (right-sided heart failure)
or cardiovascular collapse.

Question 31

What are saddle emboli?

Answer 31

Large emboli that become lodged astride the bifurcation of an artery thus blocking both branches are called saddle emboli. They classically occur at the bifurcation of the pulmonary arteries and result in sudden death.

Question 32

How do thromboemboli arise?

Answer 32

Thromboemboli in systemic arteries arise from the left heart, aneurysms and thrombi on ulcerated atherosclerosis

Question 33

Where to thromboemboli embolise?

Answer 33

They embolise to the lower extremities, brain, intestines,

kidneys, spleen and arms

Question 34

How are thrombi seen in the left heart?

Answer 34

Thrombi are often seen in the left heart as:
● Infarcts commonly affect the left ventricle. Thrombi can then form on the affected necrotic endothelium in the ventricular cavity. As the heart is beating these often
embolise.
● Atrial fibrillation results in decreased atrial contraction, dilatation of the left atrium, stagnation of blood in the left atrium and hence thrombus formation.
● Vegetations are commoner on valves of the left side of the heart (see above).

Question 35

What are paradoxical emboli?

Answer 35

They are thromboemboli that form in the systemic veins but embolism to the systemic arteries.

Question 36

How do paradoxical emboli bypass the lungs?

Answer 36

They manage to bypass the lungs in one of two ways.
1. Small emboli are able to pass through the arterio-venous anastomoses in the pulmonary circulation (these anastomoses are 20-40 times the diameter of a capillary). Incidentally, this is also the way that fat droplets pass through the lungs in fat embolism.
2. Larger emboli can only enter the systemic circulation by passing through defects in the interventricular septum or a patent foramen ovale during coughing, lifting or
straining (which increases the pressure in the right side of the heart to greater than that in the left, pushing the thrombus through the defect).

Question 37

What is atheroma?

Answer 37

Atheroma is the gruel-like necrotic material that is present in atherosclerotic plaques.

Question 38

What are TIA’s?

Answer 38

Transient ischaemic attacks (TIAs) are episodes of neurological dysfunction that appear suddenly, last minutes to hours and then disappear. They are the result of microscopic emboli, usually atheroemboli, to the brain.

The atheroembolus usually comes from the carotid arteries. Sometimes they are the result of thromboemboli that arise in the left heart. As the emboli are very small they break up quickly before any lasting damage is done
and this is why the neurological symptoms disappear after a short time.

Question 39

What causes fat and bone marrow emboli ?

Answer 39

These are usually a complication of bone fractures but fat emboli can also occur after liposuction. When a bone is fractured the bone marrow fat cells that are injured break up and release oil droplets. These coalesce over a period of a few days and are then sucked into gaping venules that have been torn by the fracture.

Question 40

What are the symptoms of fat embolism?

Answer 40

Respiratory distress and neurological symptoms are seen one to three days after the fracture. They are said to occur in 5-10% of patients with pelvic or long bone fractures and mortality is 10-15%.

Question 41

Why are respiratory symptoms seen with fat emboli?

Answer 41

Respiratory symptoms are the result of emboli that lodge in the lungs. Some droplets however will pass through the lungs in a similar way to small thromboemboli and into organs such as the brain, kidneys and skin where they will cause symptoms such as agitation, coma, renal failure and a petechial rash.

Question 42

What is air embolism?

Answer 42

There is negative pressure in the veins of the chest and head during inspiration in the upright position. These veins can draw in air after, for example, trauma of the neck and chest. A fatal amount of air is approximately 100 mls. The air is transported to the right heart where bubbles gather as a frothy mass that stops the circulation.

Question 43

What are ‘the bends’?

Answer 43

Whilst a diver is breathing air underwater (where the surrounding pressure is higher than that on land) increased amounts of gases (most importantly nitrogen) become dissolved in the blood and body tissues. If a diver surfaces too quickly, the sudden depressurisation
results in dissolved gases coming out of solution and being released into the body as bubbles.The bubbles
distort the tissues (which is very painful) and act as emboli in the blood. Nitrogen is a problem in this regard as it is fat soluble and when it comes out of solution it produces persistent bubbles and focal ischaemia in the lipid-rich tissues, such as the central nervous system, where it was previously dissolved. It also forms bubbles in skeletal muscle and joints, which are very painful, and in lung tissue. When the lungs are affected the condition is called the chokes.

Question 44

What is amniotic fluid embolism?

Answer 44

This is seen as a complication of labour and caesarean section when amniotic fluid enters the maternal circulation through a tear in the amniotic membranes. It occurs in approximately one in 50,000 deliveries and has a mortality rate of 20-40%.

Question 45

What are the symptoms of amniotic fluid embolism?

Answer 45

It causes sudden respiratory distress, hypotension, seizures, loss of consciousness and disseminated
intravascular coagulation (as amniotic fluid contains prothrombotic substances). Microscopic emboli of foetal origin (e.g., epithelial squames, lanugo hair, meconium (all of which can be present in amniotic fluid)) are found in the lungs.

Question 46

What are talcum emboli?

Answer 46

Microscopic foreign bodies with which drugs have been ‘cut’, e.g., talcum, are found in the lungs of intravenous drug abusers. These can produce a marked foreign body reaction and pulmonary symptoms.

Question 47

How is thromboembolic disease prevented and treated?

Answer 47

• General prophylaxis
• Aspirin
• Heparin
• Warfarin
• Filters

Question 48

How is general prophylaxis used to prevent and treat thromboembolic disease?

Answer 48

This can be achieved either by preventing venous stasis or by preventing hyper coagulability. To prevent stasis patients should be encouraged to mobilise early after an operation or llness. During and after an operation legs can be elevated and measures to increase venous return such as compression stockings, calf muscle stimulation, and passive calf muscle exercises can be employed. Anticoagulants are used to prevent hypercoagulability.

Question 49

How is aspirin used to prevent and treat thromboembolic disease?

Answer 49

Aspirin is antithrombogenic. It irreversibly acetylates an enzyme of prostaglandin synthesis (cyclooxygenase) and this means that platelets can’t produce thromboxane A2 which is a powerful platelet aggregator. The formation of a haemostatic plug is inhibited in patients taking aspirin and the bleeding time is prolonged. It is used in certain patients to reduce the risk of myocardial infarction and stroke. It has also been recommended as a prophylactic
against deep vein thrombosis in patients who are taking long haul flights

Question 50

How is heparin used to prevent and treat thromboembolic disease?

Answer 50

Low molecular weight heparin is used as prophylaxis against thrombosis and also to treat thrombosis. It is given subcutaneously or intravenously. It forms irreversible complexes with antithrombin III resulting in its activation.

Question 51

How is warfarin used to prevent and treat thromboembolic disease?

Answer 51

Warfarin, like heparin, is used as prophylaxis against thrombosis and also to treat thrombosis. It is an oral medication which interferes with vitamin K metabolism. The dosage required is titrated to the patients PT test results, specifically the INR results (INR stands for international normalised ratio which is the ratio of the patient’s PT to a normal control).

Question 52

How are filters used to prevent and treat thromboembolic disease?

Answer 52

Pulmonary emboli can be prevented by putting an umbrella-shaped filter in the inferior vena cava.

Question 53

Whys is thrombosis more frequent in veins?

Answer 53

Thrombosis is more frequent in veins as they have slower flow and the valves produce eddies and pockets of stagnant blood.

Question 54

What causes slow/turbulent blood flow in patients?

Answer 54

Blood flow in veins is particularly slow in:
- cardiac failure
- patients on bed rest or who are immobilised as the lack of muscular contractions in the calves results in
blood stasis.
- ulcerated atherosclerotic plaques
- within aneurysms
- around abnormal heart valves
- in the heart where a section of the myocardium isn’t contracting following myocardial infarction.

To exacerbate the problem, turbulent flow can itself produce endothelial damage. Abnormal flow also allows thrombi to grow more easily.

Question 55

When might an atheroma be release into the blood?

Answer 55

It can be released into the blood when a plaque breaks open. This can happen spontaneously and also during surgery or catheterisation for coronary artery disease. Such emboli often affect the intestine and present with abdominal pain.

Question 56

How do air emboli form during labour?

Answer 56

Air embolism can also occur during labour as air can enter the uterus and be forced into open veins during uterine contraction.

Question 57

How is the bends treated?

Answer 57

The bends is treated by prompt recompression in a special compression chamber to force the gas back into solution. The patient can then undergo slow decompression. It is important not to fly the patient to the chamber by helicopter as the atmospheric pressure is lower at altitude and even more gas will be brought out of
solution!