5 Thrombosis and Embolism Flashcards
Define thrombosis
Thrombosis:
- is the process leading to the formation of thrombus
Define thrombus
Thrombus:
- is a solid mass composed of blood constituents that have been aggregated together in blood flowing in the lumen of a blood vessel
State the main constituents of a thrombus
- Platelets
- Fibrin
Describe what occurs during the physiological formation of a thrombus
- Primary haemostasis
- Secondary Haemostasis
Describe primary haemostasis (as the first stage of physiological formation of a thrombus)
Primary haemostasis
- Vessel wall is breached
- Circulating platelets aggregate to plug the gap
- Platelets release factors that trigger the coagulation cascade
Describe secondary haemostasis (as the second stage of physiological formation of a thrombus)
Secondary Haemostasis
- Coagulation cascade converts fibrinogen to large molecules of insoluble fibrin
- Long fibrin molecules bind together platelets and entrapped white and red blood cells
Describe the course of the coagulation pathway, and how different pathways are activated, as well as how they all end in the same end result (common pathway)
The coagulation cascade is composed of the intrinsic and extrinsic pathways, which both lead to the common pathway (X -> Xa);
- where Thrombin converts fibrinogen to fibrin (clot)
Intrinsic - contact activation with collagen (Factor XII - XIIa to XI to IX to X)
Extrinsic - damage to blood vessel or release of Tissue factor (Factor VII to VIIa, X to Xa)
Common - Xa converts Prothrombin (II) to thrombin (which then converts fibrinogen to fibrin)
Define the process of Fibrinolysis
Fibrin holds thrombin together
Fibrinolysis - Fibrin is broken down, where the thrombus ‘dissolves’
- Plasmin is the active enzyme that fragments Fibrin
- The fragmented fibrin is called ‘Fibrin degradation products’ - FDP
Describe the process of Fibrinolysis
Plasma contains the inactive proenzyme plasminogen
- Plasminogen is converted to plasmin by plasminogen activators
> particularly tissue plasminogen activator (t-PA), which is secreted by endothelial cells and urokinase
When fibrin is formed, plasminogen and t-PA bind to it
- The t-PA converts nearby plasminogen to plasmin
- Which then begins to degrade the fibrin
THIS controls the size of the Thrombus
Describe the role of the feedback mechanism loops that govern the breakdown of clots, including the role of Plasmin, t-PA and other species
Plasmin makes more plasmin by t-PA
- BUT both plasmin activators (t-PA and urokinase) are inhibited by plasminogen activator inhibitor 1 + 2
- Plasmin itself is inhibited by antiplasmin
- Products of plasmin breakdown (FDP’s) also compete with thrombin to convert less fibrinogen to fibrin
Breakdown of clots occur like this
Define and describe a pathological thrombus
A pathological thrombus occurs when the thrombus enlarges beyond vessel healing requirements and continues to grow
Beyond a certain thrombus size and rate of development, the intrinsic fibrinolytic system is incapable of controlling the size to which the thrombus grows
Describe the D-dimer test
D-dimers are Fibrin Degradation Products (FDP)
- they are detected by mAb tests to D fragment
- D-dimer levels are seen to be elevated in the blood during thrombosis
This is a ‘rule-out test’
- so negative tests means coagulation isn’t activated
BUT, a positive test May mean coagulation cascade is activated, or other factors we know
Describe what a positive D-dimer test may indicate
A positive test in presence of active thrombosis:
- Pulmonary embolus
- Deep vein thrombosis (DVT)
- Aortic Dissection
BUT, this test is best used as a test of EXCLUSION
A false-positive test can be found in:
- Inflammation
- Malignancy
- Trauma
- Pregnancy
- Recent surgery
- Liver disease
Describe what factors may predispose someone to thrombus formation
Virchow’s triad:
- Damage to vessel wall - especially endothelium
- Stasis - slow or turbulent blood flow
- Hypercoagulability - change in the character of blood (especially increased platelets, increased RBC’s, increased viscosity)
Describe where a pathological thrombus occurs
- Arteries - main predisposing factors are vessel wall damage
- Veins - stasis most important (low pressure + flow systems)
- Heart
> Ventricles - chamber wall damage most important
> Atrium - stasis most important (AF)
> Heart Valves - valve surface damage most important (Endocarditis, congenital)
Describe a thrombus in an artery,
and what effect it may have on a patient
A thrombus can form an atheroma in a coronary artery
- There will be an atheromatous plaque
- There will be the thrombus (which may fill the lumen)
Effect on patient:
- Myocardium distal to this occlusion point will infarct, so the px will have a MI, and the myocardium will undergo necrosis
Describe a thrombosis in a vein,
and what effect it may have on a patient
A thrombosis can occur in a vein with no visible wall damage
Effect on the patient:
- Not the same infarction as seen in artery:
- Prevents venous drainage of a territory or organ
- Causing congestion + increased venous pressure within the organ
- This leads to infarction
- Haemorrhagic infarction
- Embolisation
Describe a thrombus on the wall of a heart,
and what effect it may have on a patient
The thrombus can form over a damaged endocardium:
- This is usually consequential on a myocardial infarction that causes thinning and disruption of the endothelium, as it heals over to form a scar
- And that then forms a nidus bethrombus
Effect on the patient:
- If thrombus stays in the ventricular cavity (nothing much) - could lead to Myocardial infarction
> severity means a reduction in the ejection of blood
- BUT the thrombus MAY break off and embolise into the systemic arterial circulation
- MOST common - L ventricular embolism is to go to the cerebral artery - stroke
Describe a thrombus on a heart valve,
and what effect it may have on a patient
A thrombus may form on the damaged endocardium of the mitral valve:
- AV valve on the left side of the heart, there may be a vegetational disruption on endothelium on the valve,
- due to infective processes
- So. there is thrombus formation on vegetation
Effect on the patient:
- LV thrombus - embolisation of the L AV valve,
- break off into systemic circulation - [Stroke]
- Coronary artery (through aortic valve) - myocardial infarction
SO, when the thrombus embolises into any organ in the systemic circulation, it can lead to damaging that organ
Describe some common outcomes for a pathological thrombus
- It may be lysed by intrinsic fibrinolysis - RARE
- It may completely block the lumen (occlusion)
- It may undergo organisation + recanalisation
- It may extend locally (propagation)
- It may fragment or detach completely + travel elsewhere in the circulation (THROMBO-EMBOLISM)
Describe what happens when a thrombus occludes a vessel?
- In an artery, thrombotic occlusion stops the flow of blood and cuts off oxygen supply - INFARCTION
- In a vein occlusion prevents drainage of tissue, blood then pools, cannot escape - CONGESTION + infarction (that is often haemorrhagic)
Describe the process of organisation of thrombi + recanalisation
- New vessels grow into the thrombus
- Vascular granulation tissue develops
- Fibroblasts invade + deposit collagen
- Fibrovascular granulation tissue develops
This is an organised thrombus.
- Sometimes, the vessels link up + some degree of recanalisation occurs
Define + describe embolism
Embolism is the transference of abnormal material by the bloodstream with eventual impaction of the material in a vessel distal to its site of origin
The most important materials to embolise are:
- Thrombus
- Cancer cells (metastasis)
Define and describe thromboembolism:
Thromboembolism
- A thrombus can break off and pass in the blood stream to a distal site, where they can impact and occlude a distal vessel
It can have a different effect, depending on whether the thrombus originates in the L or R side of the heart
- or in a systemic artery OR vein
Describe what a thrombus in an artery of the L side of the heart can embolise to
(and what distal branches may it block)
A thrombus in an artery or the L side of the heart embolises into the systemic arterial system
The thromboembolism may block distal branches:
- of Brain arteries - Stroke
- of Lower limb arteries - Gangrene of leg
- of Mesenteric arteries - Bowel infarct
- of Renal arteries - Kidney infarct
- of Splenic arteries - Splenic infarct
Describe what a thrombus in a systemic vein can embolise to
and what the impact on the patient might be
A thrombus in a systemic vein eventually embolises to a pulmonary artery (pulmonary embolism)
The impact on the patient depends on the size of the embolus:
- Small embolus - small peripheral lung infarct
- Large embolus - sudden death
Describe what a VTE risk assessment is, and its use in the clinical setting
Venous thromboembolism assessment
- given to px on entry to the hospital, as VTE is common in hospital
VTE risk assessments:
- Assess the level of mobility (as it is going to be reduced)
- Look for patient-related risk factors for thrombosis
- Look for patient-related risk factors for bleeding
So, judgements must be made to balance the risk of thrombosis vs bleeding
- in order to treat with prophylactic therapy to prevent DVT
> e.g. as much mobilisation as possible
> stockings (venous return increases)
> flowtron (inflatable cuffs on the leg that goes up and down to mimic contraction of calf muscles - to promote return of venous blood from leg - [in ICU]
Describe factors that are going to make people most likely at risk of Venous Thromboembolism
- Active cancer/cancer treatment
- Age > 60 years
- Dehydration
- Known thrombophilias
- Obesity (BMI > 30kg/m^2)
- One or more significant medical co-morbidities
> Heart disease, metabolic, endocrine or respiratory pathologies, acute infectious diseases, inflammatory conditions
Describe some other risk factors for Venous TE
- Personal history or 1st degree relative with a history of VTE
- Hormone replacement therapy (HRT)
- Use of oestrogen-containing contraceptive therapy
- Varicose veins with phlebitis
- Pregnancy or < 6 weeks post-partum
Name some other non-thrombotic materials to embolise
Thrombus and malignant tumour are the most important materials to embolise
Others include:
- Fat and marrow
- Air
- Nitrogen
- Amniotic fluid
Describe fat embolism
Long bone fracture (femur, pelvis)
- Marrow and fat can enter circulation
- can travel to the lungs
- Or systemically travel to the brain (resulting in reduced consciousness)
Describe nitrogen embolism
Rising too quickly once diving deep
- Causes gas + nitrogen to dissolve into tissues at high pressure
- Once pressure rapidly reduces, bubbles precipitate in different tissues (Boyle’s law)
To prevent this:
- decompression needs to happen slowly
Describe clinical presentations of nitrogen embolism
- Severe joint pains (in the shoulder)
- Neurological (headache, visual disturbance)
- Itchy skin, oedema skin
- Issues with the spinal cord, or paraplegia
Describe treatments for nitrogen embolism
- Hyperbaric pressure
(high pressure in a chamber - to force bubbles into solution and stop precipitating, and gradually decrease the pressure)
Describe air embolism
Air can get into circulation (introduced in cannulation in venous to outside)
- Lungs - barotrauma - too high air pressure - can enter through air spaces into blood
- Brain - dark black speck (black is air) - air in circulation in the brain
Risk
- Tubes + equipment into the coronary artery (femoral artery) - air can enter into proximal aorta + enter into the brain
Describe amniotic embolism
Rare - 1 in 20,000
Foetal cells can embolise into the maternal circulation
- this can be very bad - can lead to systemic circulatory failure - can be very serious with widespread clotting and bleeding
