9. Thrombosis and embolism Flashcards
What is a thrombus?
Solid mass formed from the constituents of the blood within the heart or vessels during life
What is thrombosis and when does it occur?
Process of formation of a thrombus. It occurs when normal haemostatic mechanisms are turned on inappropriately
What is Virchow’s triad?
He said that thrombosis depended on 3 things:
• Changes in the vascular wall (endothelial damage)
• Changes in blood flow (slow or turbulent flow)
• Changes in the blood (hypercoagulability)
It’s said that you only need 2 out of 3 from the triad to produce a thrombus.
Where do arterial or cardiac thrombi usually form?
Usually occur at a site of endothelial injury or turbulence
When do venous thrombi usually form?
Often seen where there is stasis
Why is there an increased risk of thrombi during pregnancy?
- 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
When might endothelial damage 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
- turbulent blood flow
why does endothelial damage lead to thrombi formation? When coupled with endothelial damage which is more likely to result in thrombus formation, swift blood flow or stasis of blood?
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.
Why does abnormal blood flow produce thrombi?
Gives platelets a better chance to stick to the
endothelium and clotting factors a chance to accumulate
Which blood vessels are more likely to develop thrombi and why?
More frequent in veins as they have slower flow
and the valves produce eddies and pockets of stagnant blood
There are certain patients that are more likely to suffer from thrombosis due to slow flowing blood, give examples of these ?
Blood flow will be slow in those suffering from cardiac failure meaning that they’re more at risk of thrombosis.
It is also slow in patients on bed rest or who are immobilised
Why does immobility lead to blood stasis in veins?
The lack of muscular contractions in the calves results in blood stasis
What abnormal features of the heart can cause slow/turbulent flow?
Slow/turbulent flow also occurs
- over ulcerated atherosclerotic plaques
- within aneurysms
- around abnormal heart valves
- in the heart where a section of the myocardium isn’t contracting
What role can turbulent flow have in thrombosis?
Turbulent flow can produce endothelial damage this can then allow thrombi to grow more easily.
What can cause hypercoagubility and how?
• Pregnancy and after surgery, fractures or burns
- increased fibrinogen and factor VIII
• Smoking
- activate Hageman factor (factor XII)
- some Cancers produce procoagulant substances
- The oral contraceptive pill causeshypercoagulability.
- Hypercoagulability is also seen in DIC
Which disorders can cause hypercoagubility?
Inherited disorders such as factor V Leiden, antithrombin III deficiency, protein C deficiency or protein S deficiency
Which part of blood vessels do platelets flow in and what is the implication of this?
More concentrated along the endothelium becauase they are the smallest component of blood
More likely to catch in an eddy behind a valve and aggregate
How does a thrombus form?
- Platelets aggregate.
- 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.
What is the laminated structure of a thrombus called?
Lines of Zahn -visible to the naked eye
In which vessels are the lines of Zahn more visible and why?
Arteries becuase more blood flows over the surface of the growing thrombus
Are lines of Zahn seen in post-mortem clots and why?
No, blood is not flowing.
How are post-mortem clots different to pre-mortem clots?
In post-mortem:
- no lamination (lines of Zahn)
- shiny
- rubbery
- not attached to intima
When do thrombi usually cause pain?
When they form in superficial veins
What is thrombophlebitis?
painful superficial thrombi which, as the name implies, have associated inflammation in the wall of the vein
Compare parietal and occlusive thrombi
Parietal: attached to the wall of the vessel and restrict the lumen
Occlusive: occupies the entire lumen of a vessel and obstructs blood flow
What type of thrombi tend to form in arteries?
Parietal
When do occlusive thrombi usually form in arteries?
Over a ruptured atherosclerotic plaque
What is a thrombus on a cardiac valve called?
Vegetation
Which side of the heart do vegetations usually form and why?
Valves of the left heart as they are exposed to greater pressures and therefore microtrauma which exposes the thrombogenic subendothelial tissue
In which patients is infection of vegetation common?
Intravenous drug users
What are the possible outcomes of a thrombus?
- resolution
- propagation
- organisation
- recanalisation
- embolism
How does resolution of thrombus occur and when does it most usually occur?
- Most likely when thrombi are small
- Complete dissolution of thrombus
- Fibrinolytic system active
- Blood flow re-established
What is propagation of a thrombus?
Progressive spread of thrombus in the direction of blood flow
- distally in arteries
- proximally in veins
What happens in thrombus organisation?
- reparative process
- ingrowth of fibroblasts and capillaries (similar to granulation tissue)
- lumen remains obstructed
What is thrombus recanalisation?
Of an occluding thrombus, new channels lined
with endothelium run through the occlusion and restore blood flow
- the new channels have significantly smaller capacity
What is embolisation?
Part of the thrombus breaks off and embolises
- travels through bloodstream
- lodges at distant site
Thrombi in which veins are a dangerous source of thromboemboli?
Iliac, femoral and popliteal veins
What are the most common clinical effects of thrombosis?
- Occlusion of an artery 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
- 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.
What is an embolus?
Solid, liquid or gas that is carried by the blood and is large enough to become impacted in a vascular lumen
What are thromboemboli?
emboli that arise from thrombi
Give examples of different things emboli can be composed of.
- body fat
- bone marrow
- material from atheromatous plaques
- tumour fragments
- parasites
- bubbles or air or other gases
- debris injected intravenously
- amniotic fluid
- medical equipment
- bits of brain or liver after trauma
What are the clinical effects of thrombi in arterial blood vessels?
- ischaemia
- infarction
- depends on site and collateral circulation
What are the clinical effects of thrombi in venous blood vessels?
- congestion
- oedema
- ischaemia
- infarction
Can emobli form in veins and why?
No, blood flow is from smaller to larger blood vessels
Where will objects carried by the venous blood embolise?
flow to the right heart and embolise in the pulmonary arteries
Where do most PEs arise from?
80% of pulmonary emboli arise from thrombi in the deep veins of the thigh and the popliteal vein
Compare arterial and venous thrombus
Arterial Thrombus:
- Pale
- Granular
- Lines of Zahn
- Lower cell content
Venous thrombus:
- Soft
- Gelatinous
- Deep red
- Higher cell content
What effects do small PEs have?
- most clinically silent
- multiple can cause pulmonary hypertension
Can emboli form in arteries and why?
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.
What effects do large PEs have?
More than 60% occlusion cause:
- sudden death
- cor pulmonale (right-sided heart failure)
- or cardiovascular collapse
What is a saddle embolus?
Large emboli that become lodged astride the bifurcation of an artery thus blocking both branches.
They usually occur at the bifurcation of the pulmonary arteries.
What does a pulmonary saddle embolus result in?
sudden death
Where do thromboemboli in systemic circulation arise from?
From the left heart, aneurysms and thrombi on ulcerated atherosclerosis
Where do thromboemboli in systemic circulation usually embolise?
They embolise to the lower extremities, brain, intestines, kidneys, spleen and arms.
Why do thrombi often form in the left heart?
- 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
What percentage of thromboemboli are from the heart?
80%
What are paradoxical emboli?
Thromboemboli that form in the systemic veins and embolise to the systemic arteries.
What are the complications associated with a pulmonary thromboembolism
There are different levels to a PE
1. In a massive PE…
There’s a 60% reduction in blood flow particularly if it’s a saddle emboli.
This is rapidly fatal and can cause sudden death.
- In a major PE…
Medium sized vessels are blocked.
The patients are short of breath and or cough. They produce blood stained sputum. - In a minor PE…
The small peripheral pulmonary arteries are blocked. This is asymptomatic or can produce minor shortness of breath.
It’s important to note that recurrent minor PEs can lead to pulmonary hypertension.
How might an embolus bypass the lungs in a paradoxical embolus?
- Small emboli are able to pass through the arterio-venous anastomoses in the pulmonary circulation (e.g. fat droplets)
- Larger emboli, through defects in the interventricular septum or a patent foramen ovale during coughing, lifting or straining (increases right side pressure to greater than the left, pushing the thrombus through the defect)
What form of embolus should be considered in young stroke patients and why?
Paradoxical embolus
- Stroke patients 4x more likely to have a patent foramen ovale
What are atheroma emboli?
Atheroma is the gruel-like necrotic material that is present in atherosclerotic plaques. It can be released into the blood when a plaque breaks open.
When might a atherosclerotic plaque break open?
- can happen spontaneously
- during surgery or
- catheterisation for coronary artery disease
What do atheroma emboli usually affect?
often affect the intestine and present with abdominal pain
What is a transient Ischaemic attack (TIA)? What causes them to occur? What effect does this condition have on the patient?
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.
When do bone marrow and fat emboli usually occur?
Usually a complication of bone fractures but fat emboli can also occur after liposuction
How do bone marrow and fat emboli form?
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
What are the symptoms of fat embolism and when do they appear?
respiratory distress and neurological symptoms
- seen one to three days after the fracture
How often do fat emboli from fractures occur?
Occur in 5-10% of patients with pelvic or long bone fractures and mortality is 10-15%
How do symptoms of fat emboli occur?
Respiratory symptoms are the result of emboli that lodge in the lungs.
Some droplets will pass through the lungs via arterio-venous anastomoses 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.
What are the 2 types of gas emboli?
- Air emboli
- The bends
When might air emboli form?
- trauma to chest or neck
- during labour
- IV injections, catheters
How can air emboli form in neck or chest trauma?
Negative air pressure in the veins of the chest and head during inspiration in the upright position
- These veins can draw in air after trauma
The air is transported to the right heart where
bubbles gather as a frothy mass that stops the circulation.
How can air emboli form during labour?
Air can enter the uterus and be forced into open veins during uterine contraction
What is another term for The Bends?
Decompression sickness
What happens in the bends?
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
What do bubbles formed in the bend do?
Bubbles distort the tissues (which is very painful) and act as emboli in the blood
Which gas is particularly important in the bend?
Nitrogen
What are the effects of nitrogen bubbles in the bend?
Nitrogen 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
What is it called when the lungs are affected by the bends/
The chokes (pulmonary decompression sickness)
How is the bends treated?
Treated by prompt recompression in a special compression chamber to force the gas back into solution. The patient can then undergo slow decompression
Why is it important not to fly a patient who has the bends?
Atmospheric pressure is lower at higher altitude and even more gas will be brought out of solution
What are the Predisposing factors for a DVT?
- Immobility/bed rest
- Post-operative
- Pregnancy and post-partum
- Oral contraceptives
- Severe burns
- Cardiac failure
- Disseminated cancer
When and how does amniotic embolism occur
A complication of labour and caesarean section when amniotic fluid enters the maternal circulation through a tear in the amniotic membranes
How often does amniotic embolism occur and what is the mortality
Approximately 1 in 50,000 deliveries and has a mortality rate of 20-40%
What are the symptoms of amniotic emboli?
Sudden respiratory distress, hypotension, seizures, loss of consciousness and disseminated intravascular coagulation
why does amniotic fluid embolus cause DIC?
Amniotic fluid contains prothrombotic substances (thromboplastin)
What may be found in the lungs of a patient with amniotic fluid emoblism?
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
What is talcum emboli and who are they found in?
Microscopic foreign bodies with which drugs have been ‘cut’, e.g., talcum, are found in the lungs of intravenous drug abusers.
What type of symptoms do talcum emboli produce?
These can produce a marked foreign body reaction and pulmonary symptoms
What are the five possible Prevention and Treatment of Thromboembolic Disease?
- General Prophylaxis
- Aspirin
- Heparin
- Warfarin
- Filters
How is general prophylaxis of thromboembolism achieved?
Either by preventing venous stasis or by preventing hypercoagulability
How can stasis be prevented?
- patients should be encouraged to mobilise early after an operation or illness.
- during and after an operation legs can be elevated
- measures to increase venous return such as compression stockings, calf muscle stimulation, and passive calf muscle exercises can be employed
How is hypercoagubility prevented?
Anticoagulants: aspirin, warfarin, heparin
How does aspirin work?
Aspirin is antithrombogenic. 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 and the bleeding time is prolonged
When is aspirin used?
- used in certain patients to reduce the risk of MI and stroke
- prophylactic against deep vein thrombosis in patients who are taking long haul flights.
How does heparin work?
Forms irreversible complexes with antithrombin III resulting in its activation
How is heparin administered?
subcutaneously or intravenously
When is heparin used?
used as prophylaxis against thrombosis and also to treat thrombosis.
How does warfarin work?
Interferes with vitamin K metabolism
- prevents production of vitamin K dependent clotting factors
How is warfarin dosage determined?
Dosage required is titrated to the patients PT test
results, specifically the INR results
When is warfarin used?
used as prophylaxis against thrombosis and also
to treat thrombosis
What are filters?
Pulmonary emboli can be prevented by putting an umbrella-shaped filter in the inferior vena cava.
How can DVT be treated?
- Clot Busters e.g streptokinase, ateplase (recombinant tPA)
- Intravenous heparin type drugs
- Newer generation NOAC (noval oral anticoagulants):
Dabigatran, Rivaroxaban, Apixaban, Edoxaban - Filters in IVC e.g devices in the left atria to stop thrombus formation etc.
- Embolectomy (legs etc for acute limb ischaemia)
- Oral warfarin
