Thrombosis, embolism, ischaemia and infarction Flashcards
What are arteries lined by?
Endothelial cells - a teflon coating on the inside of blood vessels
What is laminar flow?
A nice organised stream of flow with cells in the middle and plasma at the edges
Cells travel in the centre of arterial vessels and dont touch the sides
Why are clots quite rare?
Due to laminar flow and endothelial cells which are not ‘sticky’ when healthy
What happens if we damage the endothelium?
Lose teflon coating from wall of artery which contains lots of collagen which is naturally sticky to cells.
Endothelial cells lift up into stream of the blood in the vessel causing turbulent flow rather than laminar flow
What happens in turbulent flow?
Platelets heavily attracted to collagen so come in and bind to the collagen
Tell me about platelets
Positive feedback - platelet aggregation
What are the role of platelets in thrombosis
- No nucleus, derived from megakaryocytes
- Contain alpha granules and dense granules
- Alpha granules are involved in platelet adhesion, e.g. fibrinogen
- Dense granules cause platelets to aggregate, e.g. ADP
- Platelets are activated, releasing their granules when they come into contact with collagen
- If this happens within an intact vessel, a thrombus is formed
Thrombus formation
Red blood cells caught up in platelet aggregation, get entrapped causes thrombus formation
Clotting factors like fibrin - inactive form fibrinogen - polymerises into fibrin by chemicals released by platelets
More platelet aggregate more platelet aggregating factor released
More fibrin causes more fibrinogen to polymerise into fibrin
Could cause thrombus that blocks of a vessel
Thrombosis formation
- First stage is platelet aggregation, which starts the clotting cascade
- These both have positive feedback loops > hard to stop
- Thrombosis is caused by 3 major factors > Virchow’s triad
Typically thrombi are formed by 2 of these factors
Thrombosis definition
The formation of a solid mass of blood constituents formed within intact vascular system during life
How does an arterial thrombosis form?
An atheromatous plaque will result in a change in the vessel wall
1. Atheromatous plaque may have a fatty streak
2. Over time, the plaque grows and protrudes into the lumen causing a degree of turbulence in blood flow
3. This turbulence results in the loss of intimal cells
4. Fibrin deposition and platelet clumping occurs
5. Once this has started, the process is self-perpetuating, leading to the formation of the platelet layer (first layer of thrombus)
6. This layer allows for the precipitation of a fibrin meshwork in which RBCs get trapped
7. The structure protrudes further into the lumen causing more turbulence and more platelet deposition
8. Thrombi grow in the direction of blood flow propagation
What happens in venous thrombosis
- There is lower blood pressure in veins and atheroma do not occur
- lack of smooth muscle cells, no smooth muscle proliferation
- Thrombi begin at valves
- Valves produce a degree of turbulence, and can be damaged, e.g. trauma, stasis
- When blood pressure falls, flow through the veins slows, allowing for a thrombus to form
What are the clinical features of an arterial thrombosis?
-Loss of pulse distal to thrombus
-Area becomes cold, pale and painful
-Possible gangrene
The clinical features of venous thrombi
Tender
Area becomes reddened and swollen
Clinical examples of thrombosis
Myocardial infarction in LAD
Thrombosis: Virchow’s triangle
Change in vessel wall (endothelial damage)
Change in blood flow
Change in blood constituents
What is the fate of thrombi?
- Resolve
Best case scenario
Body dissolves and clears it - Organised
Becomes a scar
Results in slight narrowing of the vessel lumen - Recanalisation
Intimal cells may proliferate
Capillaries may grow into the thrombus and fuse to form larger vessels - Embolus
Fragments of the thrombus break off into the circulation
What is an embolism
Mass of material in the vascular system able to become lodged within vessel and block it.
Is the process of a solid mass in the blood being carried through the circulation to a place where it gets stuck and blocks the vessel.
What is an arterial embolism
- A Systemic embolism
- Arterial emboli can travel anywhere downstream of its entry point
- Mural thrombi in the left ventricle can go anywhere
- Cholesterol crystals from an atheromatous plaque in the descending aorta can go to any lower limb or renal artery
What is a venous pulmonary embolism?
In the venous system, emboli travel to the vena cava and lodge in the pulmonary arteries
This results in a PE
What happens in small venous emboli?
May occur unnoticed
Can cause idiopathic pulmonary hypertension
What can happen in a large venous emboli?
Can result in acute respiratory or cardiac problems
Resolve slowly
Result in chest pain and shortness of breath
What can happen in a massive emboli?
Result in sudden death
Long thrombi derived from the leg veins
Often impacted across the bifurcation of one of the pulmonary arteries
What is the most common cause of an embolus
Thrombus
e.g a deep venous thrombosis of the leg veins
which breaks off and embolises through the large veins and
right side of the heart to the lungs
What are the less common causes of an embolus?
Air, cholesterol crystals, tumours, amniotic fluid, fat
What happens if an embolus enters the venous system?
- Will travel to the vena cava through right side of heart and lodge somewhere in pulmonary arteries
- Cannot go through arterial circulation because blood vessels in lungs split down to capillary size so lungs act as a filter for any venous emboli
What is ischaemia?
Reduction in blood flow to a tissue without any other implications
What is an infarction?
Reduction in blood flow with subsequent death of cells
What is an infarction usually caused by?
Usually a macroscopic event caused by thrombosis of an artery e.g thrombus in the left anterior descending coronary artery causing infarction of the anterior wall of the left ventricle
What is a reperfusion injury?
Damage to tissue during re-oxygenation
Why are many organs very susceptible to an infarction?
Most organs in the human body have only a single artery supplying them (end arterial supply) so they are very susceptible to infarction of this supply is interrupted.
Which organs have dual arterial supply?
A few organs have a dual arterial supply so are much less susceptible to infarction: liver - with portal venous and hepatic artery supplies, lung - with pulmonary venous and bronchial artery
supplies, brain around the circle of Willis with multiple arterial supplies.
What plays the most important role in thrombosis? (Especially arterial)
Platelets
Arterial circulation
High pressure platelet rich
Venous circulation
Low pressure Fibrin rich
Driving force in venous circulation?
Fibrin
Presentations of arterial thrombosis:
Myocardial infarction
CVA
Peripheral vascular disease,
Others
Angina
Cerebral – TIA, strokes
Coronary arterial thrombosis treatment
Aspirin and other antiplatelets
LMWH or Fondraparinux – safer than heparin
Thrombolytic therapy: streptokinase, tissue plasminogen activator
Reperfusion – Catheter directed treatments and stents
Aspirin inhibits platelet function
TPA generates plasmin, degrades fibrin
What type of heparin is used usually - fractionated or unfractionated?
Unfractionated
Why not use anticoagulants here?
Increase risk of bleeding
Cerebral arterial thrombosis treatment
Aspirin, other anti-platelets
Thrombolysis
- catheter directed treatments
Reperfusion
Why is heparin not used in cerebral artery thrombosis treatment?
No heparin or systemic heparin - risk of bleeding and haemorrhage
Difference between venous and arterial circulation
Venous side lower flow smaller pressure system
Thrombosis here driven by fibrin
Where does venous thrombosis often happen?
Peripheral –Ileofemoral, femoro-popliteal
Other sites – Cerebral, Visceral
Venous thrombosis - diagnosis
Signs and symptoms-very non specific
Blood tests –D-dimer –sensitive but not specific
Imaging-usually required
What is venous thrombosis caused by?
Smoking
Trauma
What reduces venous flow?
immobility – venous flow relies on you moving
Virchow’s triad
blood flow/endothelium/blood constituents
What causes Virchow’s triad that could lead to thrombosis?
Surgery
Immobilisation
Oestrogens: OC, HRT
Malignancy - play role in immobility and endothelial damage
Long haul flights
Blood constituent problems - genetic
Factor V Leiden (5%)
PT20210A (3%)
Antithrombin deficiency
Protein C deficiency
Protein S deficiency
Anti-phospholipid syndrome
unique coagulation defect which predisposes arterial thrombosis
Venous thrombosis treatment
Heparin or LMWH
Warfarin
DOAC
Endo-vascular
Surgical
When would treatment of DVT be more aggressive?
When its big enough to cause a PE
Prevention of venous thrombosis:
Mechanical or chemical thromboprophylaxsis
Also early mobilisation and good hydration
What can we do to encourage blood flow – get them moving also use compression stocking – helps with venous return – encourages blood flow
Heparin
Glycoaminoglycan
Binds to antithrombin and increases its activity
Indirect thrombin inhibitor
most important anticoagulant
short half life 4 hours
Monitor with APTT, aim ratio 1.8-2.8
Given by continuous infusion
Low molecular weight heparin (LMWH)
Smaller molecule, less variation in dose and renally excreted
Once daily, weight-adjusted dose given subcutaneously
Used for treatment and prophylaxsis
Don’t need to monitor them as half life is predictable – have to take renal function into account – otherwise accumulation of LMWH
What is HIT?
heparin induced thrombocytopenia
if you give heparin if they’ve had in the past high doses of heparin then at higher risk of Developing HIT – affects platelets – platelet count really drops – drops drastically
Warfarin
Orally active
Prevents synthesis of active factors II, VII, IX and X (1972)
Antagonist of vitamin K
Long half life (36 hours)
Prolongs the prothrombin time
Difficult to use
Need to monitor
Reverse by giving vitamin K
New Oral Anticoagulant Drugs (NOAC/DOAC)
Orally active – like aspirin and warfarin
Directly acting on factor II or X
No blood tests or monitoring
Shorter half lives
Used for extended thromboprophylasis and treatment of AF and DVT/PE ( equivalent to INR 2-3, not higher, so not heart valves)
Not used in pregnancy
Where are NOAC/DOAC’s not used?
Metal heart valves - risk of thrombosis is really high
Pregnancy
Aspirin
Inhibits cyclo-oxygenase irreversibly
Act for lifetime of platelet, 7-10 days
Inhibits thromboxane formation and hence platelet aggregation
Used in arterial thrombosis, 75-300 mg od
Other antiplatelets
Clopidogrel -inhibits ADP induced platelet aggregation by irreversibly binding to the p2y12 receptors
Ticagrelor – p2y12 receptor antagonist
Prasugrel – p2y12 receptor antagonist
DVT/ PE
Deep vein of the legs
Normal blood flow in vein
Blood clot (thrombus) occurs - deep vein thrombosis
DVT incidence
25,000 people a year die of DVT and PE a year in UK
50% preventable, premature mortality
More than RTA, AIDS and breast cancer combined
Risk factors for DVT
Surgery,
immobility,
leg fracture
POPOC pill,
HRT,
Pregnancy
Long haul flights/ travel (rare)
inherited thrombophilia- genetic predisposition; 5% population, familial
Signs and symptoms of DVT
Symptoms: leg pain, swelling
Signs: tenderness, swelling, warmth, discolouration
Complications of DVT
Phlegmasia alba dolens and phlegmasia cerulae dolens, PE
Why does a DVT lead to ischaemia?
rare complication – does happen – can cause limb loss – you get all the veins thrombosed – all small tibial veins thrombose – leads in increased compartment pressures – causes pressure of small arterioles leading to ischaemia/ infarction – massive rise in compartment pressure
Investigations for DVT?
D-dimer: normal excludes diagnosis
positive does not confirm diagnosis
Ultrasound compression – gold standard
CT or MR venogram
catheter venogram
DVT treatment
LMW Heparin s/c od for min 5 days
Oral warfarin, INR 2-3, (2.5) for 3-6 months
DOAC/NOAC
Compression stockings
Treat/ seek underlying cause: malignancy, thrombophilia, compression
Re-cannalisation
Endovenous:
Chemical
Mechanical
Mechanico-chemical
Stents – used all the time – in venous side stents evolving and developing
Prevention of DVT
Mechanical- hydration and early mobilisation, Compression stockings, Foot pumps
Chemical- LMW Heparin
Who are at high risk for thromboprophylaxis?
hip and knee, pelvis, malignancy, risk factors, prolonged immobility
All immobile medical, many surgical/ O+G Daltrparin s/c od. No monitoring
What is pulmnary embolism
A consequence of DVT – clot breaks up and goes up to the lungs – when these patients present with suspicion of PE – most likely DVT underlying
Symptoms of PE?
breathlessness
pleuritic chest pain
may have signs/ symptoms of DVT
may have risk factors
no other diagnosis more likely
Signs of PE?
tachycardia
tachypnoea
pleural rub
those of precipitating cause
none of alternative diagnosis
Differential diagnosis of PE?
chest pain and sob
Consider also musculoskeletal, infection, malignancy, pneumothorax, cardiac, gastro causes
PE initial investigations
CXR usually normal
ECG sinus tachy, (QI,SI,TIII)
Blood gases: type 1 resp failure, decreased O2 and CO2
Mainly done to exclude alternative causes
Further investigations of PE?
D-dimer: normal excludes diagnosis
CTPA spiral CT with contrast, visualise major segmental thrombi
Ventilation/ Perfusion scan: mismatch defects
Treatment of PE
Supportive treatment
LMW Heparin s/c od weight adjusted 5/7
Oral warfarin INR 2-3 (2.5) for 6 months
DOAC
Treat underlying cause
Prevention of PE
Early mobilisation and hydration
Mechanical
Chemical
IVC filters
Anticoagulation
