Thrombosis and Embolism (Session 5) Flashcards
1
Q
What is a thrombus?
A
- A solid mass formed from the constituents of blood
- within the circulatory system (heart or vessels)
- during life.
2
Q
Why is thrombosis technically not the same as a ‘clot’?
A
- Thrombosis forms inside the circulatory system (heart or vessels) and a clot is a mass of blood formed outside the vessel wall
3
Q
What is thrombosis?
A
Thrombosis is the process of formation of a thrombus.
4
Q
When does thrombosis occur?
A
When normal haemostatic mechanisms are turned on inappropriately.
5
Q
What did Virchow state?
A
Thrombosis depends 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 (hypercoagulability)
6
Q
What are the 3 components of Virchow’s triad?
A
- Changes in the vascular wall (endothelial damage)
- Changes in blood flow (slow or turbulent flow)
- Changes in the blood (hypercoagulability)
7
Q
Where do arterial or cardiac thrombi usually occur?
A
- At a site of endothelial injury
- At a site of turbulence.
8
Q
Where are venous thrombi often seen?
A
where there is stasis (slowing or pooling of blood)
9
Q
1) What is enough to produce a thrombus (in regards to Virchow’s triad?
2) Give an example
3) Where are these 2 things present?
A
- Two of three from the triad are enough to produce a thrombus
2) e.g., stasis and hypercoagulability without endothelial damage will result in a thrombus.
3) In pregnancy
10
Q
What are pregnant women at an increased risk of?
Why?
A
1) Increased risk of thrombi in the lower limbs in pregnancy.
2) 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.
11
Q
Give 6 examples of when endothelial damage can occur
A
- After myocardial infarction (there is damage to the 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.
12
Q
Describe how endothelial damage can lead to thrombus formation
A
- As in clotting, 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.
13
Q
1) What effect does slow blood flow have on the thrombus formation? (3)
2) Therefore where is thrombosis more commonly seen?
A
1)
- Gives platelets a better chance to stick to the endothelium
- Gives clotting factors a chance to accumulate.
- Allows thrombi to grow more easily.
2) Thrombosis is more frequent in veins as…
- They have slower flow
- The valves produce eddies and pockets of stagnant blood.
14
Q
Name 2 patients that are predisposed to thrombosis aside from pregnant women
Describe why
A
- Patients with cardiac failure
- Patients patients on bed rest or who are immobilised
Why?
- Because patients with cardiac failure have slow blood flow
- Patients on bedrest have slow blood flow as the lack of muscular contractions in the calves results in blood stasis.
15
Q
1) What can cause blood stasis? (3)
2) What can cause turbulent blood flow? (5)
A
1)
- Narrowing of the arteries (ie due to atherosclerosis forming or due to arterosclerosis)
- Conditions where we have low blood pressure (ie cardiac failure)
- Immobility (due lack of muscular contractions in the calfs ie)
2)
- Defects in heart wall (ie atherosclerosis causing indentations)
- Defects and heart valves (ie calcification of heart valves)
- Aneurysms
- Atrial fibrillation (irregular heart beat)
- Area of dead cardiac muscle (ie after MI)
16
Q
What can turbulent blood flow itself produce?
A
endothelial damage.
17
Q
1) In pregnancy, after surgery, fractures or burns, what are there increased circulating levels of?
2) This means that the blood is…
A
1) Fibrinogen and factor VIII (8)
2) Hypercoagulable
18
Q
Which conditions result in more hyper coagulable blood? (9)
A
- Pregnancy
- After surgery
- After fractures
- After burns
- Smoking
- Some cancers produce procoagulant substances
- The oral contraceptive pill, particularly older preparations, causes hypercoagulability
- DIC
- Inherited disorders
19
Q
Why does smoking lead to hypercoaulability?
A
as it is known to activate Hageman factor (factor XII)
20
Q
Name some inherited disorders that can led to hypercoagulability (4)
A
- Factor V Leiden
- Antithrombin III deficiency
- Protein C deficiency or protein S deficiency
21
Q
Describe how thrombus formation occurs
A
- Platelets are the smallest formed elements in the blood and so they are more concentrated along the endothelium (similar to water in a stream carrying pebbles and sand – the pebbles flow in the centre of the stream and the sand is deposited along the banks).
- 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.
- As in haemostasis fibrinogen binds the platelets together and fibrin grows out of the platelet layer. The fibrin traps red blood cells.
- In this way a white layer of platelets is covered by a red layer of fibrin and red blood cells. The surface of the red layer is thrombogenic and platelets stick to the exposed fibrin.
- A second white layer of platelets forms and the process continues.
22
Q
1) What kind of structure is a thrombus?
2) The laminations…
3) What are they called?
4) Where are they more obvious?
A
1) A laminated structure
2) Are visible to the naked eye
3) Lines of Zahn
4) In arterial thrombi, as opposed to venous thrombi, as blood flows over the surface of the forming thrombus in arteries.
23
Q
Compare post-mortem clots to pre-mortem clots
A
- Post-mortem clots which form when blood is not flowing are not laminated
- More rubbery and shiny than pre-mortem thrombi
- Are not attached to the intima
24
Q
Why is it important for pathologists to be able to differentiate between pre-mortem and post mortem ‘clots’?
A
so that they can be sure when death is due to a thrombus or thromboembolism.
25
1) Is pain always present when a thrombus forms?
2) What type of thrombus formation usually causes pain?
3) What do you call this?
1) No
2) When thrombi form in superficial veins
3) Thrombophlebiti
26
What is Thrombophlebitis?
- Painful superficial thrombi which have associated inflammation in the wall of the vein.
27
1) What are the 2 types of thrombi?
2) Describe them
3) What do arterial thrombi tend to be like?
4) When occlusive thrombi do form in an artery, it tends to be over...
5) Describe such thrombi in coronary arteries
1) Parietal
Occlusive
2) - Parietal - Attached to the wall of the vessel and restrict the lumen
- Occlusive - when they fill and obstruct the lumen.
3) Parietal
4)over an atherosclerotic plaque that has cracked open
5) no bigger than a match head but can be fatal.
28
1) What do you call a thrombus on a cardiac valve?
2) Describe them
3) Where do they usually form and why?
4) What can happen to them?
5) Which group of people is this particularly common in?
1) Vegetation
2) They can be 2-3 cm long and they easily embolise.
3) 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.
4/5) They can become infected and this is particularly common in intravenous drug abusers.
29
State the 5 outcomes for thrombi
- Resolution
- Propagation
- Organisation
- Recanalisation
- Embolisation
30
What is thrombi resolution?
the thrombus is dissolved
31
What is thrombi propagation?
the thrombus grows
32
What is thrombi organisation?
- The thrombus undergoes fibrous repair and forms a fibrous scar on the wall of
the vessel
33
What is thrombi recanalisation?
- 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
34
What is thrombi embolisation?
- 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.
35
Describe the most common clinical effects of thrombosis
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.
36
What is an embolus?
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.
37
What is embolism?
Sudden blocking of an artery by a thrombus or foreign material which has been brought to its site of lodgement by the blood current (the impaction of an embolus)
38
What are Thromboemboli?
Describe them
- 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.
39
What can emboli be composed of? (10)
- Body fat
- Bone marrow
- Material from atheromatous plaques
- Tumour fragments
- Parasites
- Bubbles of air or other gases
- Debris injected intravenously
- Amniotic fluid
- Medical equipment
- Bits of brain or liver after trauma
40
Describe emboli in veins
- 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.
41
Describe emboli in arteries
- 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
42
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).
43
1) What are most pulmonary emboli like?
2) What can multiple small pulmonary emboli cause?
1) Small and clinically silent
2) Pulmonary hypertension
44
What will large pulmonary emboli, resulting in more than 60% occlusion of the pulmonary circulation cause? (3)
- Sudden death
- Cor pulmonale (right-sided heart failure) or
- Cardiovascular collapse
45
1) What are saddle emboli?
2) Where do they classically occur?
3) What do they result in?
1) Large emboli that become lodged astride the bifurcation of an artery thus blocking both branches
2) at the bifurcation of the pulmonary arteries
3) Sudden death.
46
1) What do thromboembolism in systemic arteries arise from?
2) Where do they embolise to?
1) Left heart, aneurysms and thrombi on ulcerated atherosclerosis.
2) the lower extremities, brain, intestines, kidneys, spleen and arms.
47
Thrombi are often seen in the left heart as:
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).
48
80% of systemic thromboemboli are from...
cardiac mural thrombi (in association with a
myocardial infarction or atrial fibrillation).
49
How common are paradoxical emboli?
Rare
50
What are paradoxical emboli?
They are thromboemboli that form in the systemic veins but embolise to the systemic arteries.
51
Describe the 2 ways that paradoxical emboli are able to bypass the lungs
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).
52
1) What should be considered when a young patient presents with an ischaemic stroke?
2) Why should this be considered
1) paradoxical embolus
2) patients with a stroke are four times more likely to have a patent foramen ovale when compared with the general population. Therefore, a paradoxical embolus should be a consideration when a young patient presents with an ischaemic stroke.
53
1) What is atheroma and where is it present?
2) What happens when a plaque containing atheroma breaks open?
3) When can a plaque containing atheroma break open?
4) What are the effects of emboli on the intestine?
1) Atheroma is a gruel-like necrotic material present in atherosclerotic plaques.
2) Atheroma can be released into the blood when a plaque breaks open.
3) A plaque containing atheroma can break open spontaneously or during surgery or catheterisation for coronary artery disease.
4) Emboli often affect the intestine and present with abdominal pain.
54
What does TIA Stand for?
Transient Ischaemic Attacks (TIAs)
55
What is a Transient ischaemic attack (TIAs)?
episodes of neurological dysfunction that appear suddenly, last minutes to hours and then disappear.
56
1) What causes TIAs?
2) Where does the atheroembolus usually come from?
3) What are they sometimes the result of?
4) Why do neurological symptoms disappear after a short time?
1) TIAs are usually caused by microscopic emboli, usually atheroemboli, to the brain.
2) The atheroembolus usually comes from the carotid arteries.
3) Thromboemboli that arise in the left heart.
4) Neurological symptoms disappear after a short time because the emboli are very small and break up quickly before any lasting damage is done.
57
What are fat and bone marrow emboli?
Fat and bone marrow emboli are clumps of fat and bone marrow cells that travel through the bloodstream and can block blood vessels.
58
What are bone marrow and fat emboli usually a complication of?
When else can they occur?
- Usually a complication of bone fractures
- After liposuction can also occur
59
Describe how fat and bone marrow emboli are formed
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.
60
What kind of symptoms are seen in fat embolism? When do symptoms occur?
Symptoms of fat embolism, such as respiratory distress and neurological symptoms, typically occur one to three days after a bone fracture.
61
1) Why do people with fat embolsim experience respiratory symptoms?
2) What may some droplets do?
3) What symptoms may this lead to?
1) Respiratory symptoms are the result of emboli that lodge in the lungs.
2) 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 (see above) and into organs such as the brain, kidneys and skin
3) agitation, coma, renal failure and a petechial rash.
62
What are the 2 types of air embolism
1) Gas embolism
2) The bends
63
1) Describe how air embolism can occur
2) What is a fatal amount of air to draw in?
3) What happens to the air that is drawn in?
4) When else apart from after trauma can air embolism occur?
1) 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.
2) 100ml
3) The air is transported to the right heart where bubbles gather as a frothy mass that stops the circulation.
4) can also occur during labour as air can enter the uterus and be forced into open veins during uterine contraction.
64
Describe the bends in the vein of gas emboli
- 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 (rather like the bubbles seen when a bottle of champagne is opened).
- The bubbles distort the tissues (which is very painful) and act as emboli in the blood.
65
1) In 'the bends', which gas is a particular problem?
2) Describe the issues it leads to
3) What is the bends called when the lungs are affected ?
1) Nitrogen
2) 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.
3) The chokes
66
1) Describe how 'the bends' is treated
2) What is it important to remember?
3) What is the posture of sufferers with the bends like?
1) by prompt recompression in a special compression chamber to force the gas back into solution. The patient can then undergo slow decompression
2) t 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!
3) Arched back
67
What is amniotic fluid embolism?
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.
68
What symptoms does amniotic fluid embolism cause?
It causes sudden respiratory distress, hypotension, seizures, loss of consciousness and disseminated intravascular coagulation (as amniotic fluid contains prothrombotic substances).
69
Where are Microscopic emboli of foetal origin found?
Give 2 examples
1) In the lungs
2) (e.g., epithelial squames, lanugo hair, meconium (all of which can be present in amniotic fluid))
70
Describe talcum emboli and where they are found
What can they lead to?
1) Microscopic foreign bodies with which drugs have been ‘cut’, e.g., talcum, are found in the lungs of intravenous drug abusers.
2) These can produce a marked foreign body reaction and pulmonary symptoms.
71
Give 5 means of Prevention and Treatment of Thromboembolic Disease
- Generalprophylaxis
- Asprin
- Heparin
- Warfarin
- Filters
72
Describe general prophylaxis of throembolic disease
- This can be achieved either by preventing venous stasis or by preventing hypercoagulability.
- To prevent stasis patients should be encouraged to mobilise early after an operation or illness.
- 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 (see below) are used to prevent hypercoagulability.
73
Describe the role of aspirin in Prevention and Treatment of Thromboembolic Disease
- 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.
74
Describe the role of heparin in Prevention and Treatment of Thromboembolic Disease
- 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
75
Describe the role of warfarin in Prevention and Treatment of Thromboembolic Disease
- Warfarin, like heparin, is used as prophylaxis against thrombosis and also to treat thrombosis.
- Oral medication which interferes with vitamin K metabolism.
- The dosage required is titrated (adjusted) 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).
76
Describe the role of filters in Prevention and Treatment of Thromboembolic Disease
- Pulmonary emboli can be prevented by putting an umbrella-shaped filter in the inferior vena cava.
77
Damage to vessels histology
