Thrombosis and Embolism (Session 5) Flashcards
What is a thrombus?
- A solid mass formed from the constituents of blood
- within the circulatory system (heart or vessels)
- during life.
Why is thrombosis technically not the same as a ‘clot’?
- Thrombosis forms inside the circulatory system (heart or vessels) and a clot is a mass of blood formed outside the vessel wall
What is thrombosis?
Thrombosis is the process of formation of a thrombus.
When does thrombosis occur?
When normal haemostatic mechanisms are turned on inappropriately.
What did Virchow state?
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)
What are the 3 components of Virchow’s triad?
- Changes in the vascular wall (endothelial damage)
- Changes in blood flow (slow or turbulent flow)
- Changes in the blood (hypercoagulability)
Where do arterial or cardiac thrombi usually occur?
- At a site of endothelial injury
- At a site of turbulence.
Where are venous thrombi often seen?
where there is stasis (slowing or pooling of blood)
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?
- 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
What are pregnant women at an increased risk of?
Why?
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.
Give 6 examples of when endothelial damage can occur
- 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.
Describe how endothelial damage can lead to thrombus formation
- 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.
1) What effect does slow blood flow have on the thrombus formation? (3)
2) Therefore where is thrombosis more commonly seen?
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.
Name 2 patients that are predisposed to thrombosis aside from pregnant women
Describe why
- 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.
1) What can cause blood stasis? (3)
2) What can cause turbulent blood flow? (5)
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)
What can turbulent blood flow itself produce?
endothelial damage.
1) In pregnancy, after surgery, fractures or burns, what are there increased circulating levels of?
2) This means that the blood is…
1) Fibrinogen and factor VIII (8)
2) Hypercoagulable
Which conditions result in more hyper coagulable blood? (9)
- 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
Why does smoking lead to hypercoaulability?
as it is known to activate Hageman factor (factor XII)
Name some inherited disorders that can led to hypercoagulability (4)
- Factor V Leiden
- Antithrombin III deficiency
- Protein C deficiency or protein S deficiency
Describe how thrombus formation occurs
- 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.
1) What kind of structure is a thrombus?
2) The laminations…
3) What are they called?
4) Where are they more obvious?
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.
Compare post-mortem clots to pre-mortem clots
- 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
Why is it important for pathologists to be able to differentiate between pre-mortem and post mortem ‘clots’?
so that they can be sure when death is due to a thrombus or thromboembolism.
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
What is Thrombophlebitis?
- Painful superficial thrombi which have associated inflammation in the wall of the vein.
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.
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.
State the 5 outcomes for thrombi
- Resolution
- Propagation
- Organisation
- Recanalisation
- Embolisation
What is thrombi resolution?
the thrombus is dissolved