Haemostasis, Thrombosis and Embolism Flashcards
What does haemostasis do?
Stop blood
What does successful haemostasis depend on?
The vessel wall
Platelets
Coagulation system
Fibrinolytic system
What does the coagulation system do?
Promotes the formation of a solid mass of blood
What does the fibrinolytic system do?
Acts against the coagulation system to make sure that you don’t end up with too much blood clotting
Why are tight control mechanisms required?
To ensure that there’s no over- or under- activity
How to blood vessels contribute to haemostasis?
They constrict to reduce blood loss
How does constriction of blood levels contribute to haemostasis?
If the hole is made smaller, they reduce the volume of blood coming out
Which vessels can contribute to reducing the amount of blood loss?
All
What are platelets?
Subcellular fragments
What are platelets derived from?
Cells in the bone marrow called megakaryocytes
What to platelets do?
Adhere to one another and to the damaged vessel wall, promoting the coagulation of blood.
They participate in the platelet release reaction.
What is the purpose of the platelet release reaction?
Once the platelets are stuck, they release certain molecules that are helpful in forming and expanding the platelet plug, and activating the coagulation system
What happens in the platelet release reaction?
ATP is converted to ADP (and therefore this is an energy dependant reaction). The ADP, along with thromboxane A2, cause platelet aggregation. 5HT and platelet factor 3 are also released
Why is PF3 important in coagulation?
It activates the cascade mechanism aiming to produce fibrin
What happens to platelets after aggregation?
They coalesce
How does coagulation occur?
As a cascade, with amplification
What happens in the coagulation cascade?
A series of inactive components are converted to active components.
Prothrombin is converted to thrombin, which is then used to convert fibrinogen to fibrin
What is fibrin?
A solid mass that’s formed at the end of coagulation cascade, that has a major contribution to the process of haemostasis
How can the coagulation cascade be useful therapeutically?
It can be manipulated to have the desired effect
How much blood is needed to produce enough thrombin to convert all the fibrinogen in the body to fibrin?
1ml
Why is tight regulation of the clotting cascade required?
If left unchecked, the blood would go solid
What is needed to regulate coagulation?
A balance of procoagulant and anticoagulant forces
What controls coagulation?
Thrombin inhibitors
Fibrinolysis
Endothelium
What are thrombin inhibitors?
Things that reduce the action of thrombin
Give 5 examples of thrombin inhibitors
Antithrombin III α1 anti-trypsin α2 macroglobulin Protein C Protein S
What may inherited deficiency of antithrombin III lead to?
Thrombosis
What may inherited deficiency of protein C and S lead to?
Thrombosis
What is fibrinolysis?
The breakdown of fibrin
How is plasminogen converted to plasmin?
By plasminogen activators
Where is fibrinolytic therapy used?
To enhance the fibrinolytic mechanism, getting stuff to break down
Give 2 examples of fibrinolytic factors
Streptokinase
tPA
What anti-coagulation mechanisms does endothelium have?
Plasminogen activators
Prostacyclin
Nitric oxide
Thrombomodulin
What is thrombosis?
The formation of a solid mass of blood within the circulatory system during life
Why can thrombosis be hard to identify?
Can sometimes be hard to tell if thrombus formed before or after death
What can thrombosis occur due to?
Abnormalities in vessel wall
Abnormalities in blood flow
Abnormalities of blood components
What abnormalities in the vessel wall can cause thrombosis?
Atheroma
Direct injury
Inflammation
What abnormalities in blood flow can cause thrombosis?
Stagnation
Turbulence
What abnormalities of blood components can lead to thrombosis?
Alteration of coagubility of blood
What can alter the coagubility of blood?
Smokers
Post-partum
Post-op
Why is the coagubility of blood altered post-partum?
There needs to be a good haemostatic mechanism, as after a baby, there is a raw area where the placenta has come away that’s prone to haemorrhage
How to arterial thrombi appear?
Pale Granular Lines of Zahn Lower cell content Still have residual lumen Curved shape on either side
What produces lines of Zahn?
The tendency to get lying down of layers
How does the cell content of arterial thrombi differ from arterial?
Arterial have lower cell content, but more fibrin
What does the appearance of arterial thrombi depend on?
Particular constituents of blood
Why do arterial thrombi have a curved shape on either side?
Where the artery has swollen and bulged out
How do venous thrombi appear?
Soft
Gelatinous
Deep red
Higher cell content
What are the potential outcomes of thrombosis?
Lysis Propagation Organisation Recanalistion Embolism
What is likely to be happening with regards to thrombi at all times in the body?
They are being formed, but get dealt with so don’t get bigger
What happens in lysis of thrombi?
Complete dissolution
When does lysis of thrombi occur?
When the fibrinolytic system is active
What happens when lysis of thrombi occur?
Blood flow is re-established
When is lysis of thrombi likely?
When thrombi are small
What is propagation of thrombi?
The progressive spread of thrombosis
What happens in propagation of thrombi?
It gets bigger in the direction of blood flow, so away from the starting point
What is the result in propagation of thrombi?
The thrombi spreads distally in arteries, and proximally in veins
What happens when you get a thrombus in a vein?
Up until the next vein joints, there is stagnation of the blood- no movement, as there is a blockage, so nothing pushing it. When you get the next branch coming in, there is turbulent flow, due to there being no normal flow behind, so there if formation of a new thrombus. This starts a chain reaction, giving an increase in size of thrombus
What is the problem with thrombi in veins?
As you move back towards the heart, the veins get bigger, so ones that are blocked get bigger, and so does the thrombus. This means that you can get a thrombus that occludes the femoral veins
What happens to the size of the thrombus in propagation?
It gets wider, not longer
What can happen to a propagated thrombus?
It can become detached, forming an embolus
What happens in organisation of thrombi?
Reparative process, where you get an ingrowth of fibroblasts and capillaries
What does organisation of thrombi lead to?
The formation of scar tissue
What is the problem with organisation of thrombi?
The lumen continues to be obstructed, and there is no restoration of flow
What happens in recanalisation of thrombi?
Blood flow is re-established, but incompletely, as one or more channels is formed through organising thrombus
What is the result of recanalisation?
Means you don’t get the same level of flow as you would through normal lumen
What happens in embolism?
Part of the thrombus breaks off, travels through blood stream and lodges at a distant site
When does a pulmonary embolism occur?
When a thrombus starts in deep veins, breaks off, gets to heart and lodges in lungs
What does arterial thrombosis lead to?
Ischaemia and infarction
Why does arterial thrombosis lead to ischaemia and infarction?
Because there is reduced flow to artery, so eventually the tissue supplied by that artery will die
What does the final outcome of arterial thrombosis depend on?
The exact site
If collateral circulation has developed
When is the development of collateral circulation more likely to have occurred?
When there’s been a progressive increase in arterial disease
What is more likely with a sudden occlusion of a previously healthy artery?
The outcome of ischaemia and infarction
What is the problem with functional end arteries?
They have no collateral circulation, so if they get blocked, theres nothing else that can supply blood
What does venous thrombosis lead to?
Congestion and oedema
Why do venous thrombosis lead to congestion and oedema?
Because they’re unable to drain the tissue, so there’s an increase in hydrostatic pressure in the vessels, eventually producing stagnant flow
What must happen before veins can push fluid out of them?
There must be sufficient hydrostatic pressure for blood to get to tissue via veins
What happens if pressure builds reaching arterial pressure?
There will be no flow, and therefore ischaemia and infarction will occur
What is an embolism?
A blockage of a blood vessel by a solid, liquid or gas at a site distant from it’s origin
What types of emboli are there?
Thrombo-emboli Air Amniotic fluid Nitrogen Medical equipment Tumour cells Cholesterol
What % of emboli are thrombo-emboli?
> 90%
How much air is needed to give an air embolism?
About 150ml
When can a large amount of air enter the bloodstream?
If the jugular is cut
What can a jugular cut lead to?
It can produce froth, which cannot be pumped around the circulatory system
When do amniotic fluid embolisms occur?
In illegal terminations of pregnancies
Can also occur after normal pregnancies or miscarriage
When do nitrogen emboli occur?
When you come up to quickly after diving
Why do nitrogen emboli occur when you come up too quickly after diving
Because the nitrogen comes out of the blood, giving gaseous nitrogen which can get stuck
How can medical equipment cause an embolus?
Can break off, circulate and get stuck somewhere
What happens when you block an arterial channel?
There is always a risk damage
What happens to thrombo-emboli from systemic veins?
They pass to the lungs, causing pulmonary emboli
What happens to thrombo-emboli from the heart?
They pass via the aorta to renal, mesenteric, or any other artery
What happens to thrombo-emboli from atheromatous carotid arteries?
They pass to the brain
What happens to thrombi-emboli from an atheromatous abdominal aorta?
They pass to the arteries of the legs
What are the predisposing factors to a deep vein thrombosis?
Loosing the calf pump, so if legs aren’t moving normally
Things causing hypercoagubility
Cardiac failure
Disseminated cancer
What can cause the loss of the calf pump
Immobility/bed rest
Any long journey where legs are compressed
What causes hypercoagubility?
Pregnancy Post-partum
Oral contraceptive
Severe burns
Why does the oral contraceptive cause hypercoagubility?
Oestrogen affects coagulation
What must happen if a patient is at high risk of DVT?
They must be identified and offered prophylaxis
What prophylaxis might a patient at high risk of DVT be given?
Sub-cutaneous heparin
How can DVT be prevented during surgery?
Using leg compression, which mimics the muscular pump of the calves, expelling blood from the venous circulation so you don’t get a stagnation effect
How are DVTs treated?
IV heparin
Warfarin
What does IV heparin do?
Prevents the thrombus from getting bigger, but doesn’t dissolve it
What does warfarin do?
Inhibits certain coagulation factors
Reduces opportunity for thrombus to get bigger
What constitutes a massive pulmonary embolism?
> 60% reduction in blood flow
What is the outcome of a massive PE?
It’s rapidly fatal
What constitutes a major PE?
When medium sized vessels are blocked
What are the symptoms of a major PE?
Shortness of breath
May cough
Blood stained sputum
What constitutes a minor PE?
When a small peripheral pulmonary artery is blocked
What are the symptoms of a minor PE?
May be asymptomatic
Present with minor shortness of breath
Who do minor PE’s occur particularly in?
Young, fit people
When may minor PE’s have an impact?
If already have CVS or pulmonary problems
What do recurrent minor PE’s lead to?
Pulmonary hypertension
What does cerebral embolisms occur with?
Carotid atheroma
What happens in a cerebral embolism?
Piece of thrombus formed on atheromatous plaque moves up into cerebral circulation
What gives a warning of a cerebral embolism?
Where really tiny bits of thrombus produces a transient ischaemic attack
What must be done if someone has a TIA?
They must be anti-coagulated to reduce risk of stroke
May have carotid surgery
When do fat embolisms occur?
When a long bone gets broken, and some of the fat (sometimes bone marrow) gets into the circulation
How can fat embolisms present?
Profound neurological problems
Confusion
