Session 5 - Haemostasis Flashcards
How is an appropriate level of haemostasis achieved?
-Through the balance of procoagulants and anticoagulants
What is the result of increased anticoagulants?
-Excessive bleeding (haemophilia)
What is the result of excessive procoagulants?
-Thrombosis
What are the main factors in haemostasis?
- Vessel walls
- Platelets
- Coagulation system
- Fibrinolytic system
What is the mechanism of haemostasis?
1) Severed artery contracts which decreases the pressure down stream to limit flow
2) Fragile primary haemostatic plug of activated platelets forms in seconds to minutes, sticking to the injured vessel and surrounding CT
3) Secondary haemostatic plug forms as fibrin filaments stabilise the platelet plug (approx 30 mins)
What becomes of a secondary haemostatic plug?
-Becomes organised and replaced by granulation tissue and a small scar
What is the problem for haemostasis for people with a los platelet count or non-functional platelets?
-They cannot form the primary haemostatic plug
What is the problem for haemostasis in haemophiliacs?
-They cannot form the secondary haemostatic plug as they have functioning platelts but impaired clotting so cant produce fibrin
What do platelets adhere to within the damaged vessel and how?
-Adhere to the subendothelium, specifically to von willebrand factor which is concentrated on the subendothelium basement membrane
How does the haemostatic plug grow?
- Aggregation with other platelets which are stabilised by fibrin
- Swelling
- Secretion of factors which aid clotting
List some factors secreted by platelets which aid clotting
- Fibrinogen
- ADP (activates more platelets)
- Thromboxane A2 (powerful platelet aggregator)
List some platelet activators
- ADP
- Collage surfaces in extravascular areas
- Thrombin
- Adrenaline
What role does serotonin (5-HT) play in haemostasis?
-Vasoconstrictor
Why is tissue factor important in haemostasis?
-Exposed in damaged BVs and initiates extrinsic clotting cascade
What activates fibrinogen?
-Thrombin proteolytically cleaves fibrinogen to fibrin
Why is thrombin under high control?
-It cannot circulate in an active state or blood would be solid
What is the difference between the activation of intrinsic and extrinsic pathways of clotting?
- Intrinsic -> Triggered by a negatively charged surface eg glass/subendothelium -> no vessels need to be broken open
- Extrinsic -> activation relies on tissue factor from damaged cells bring released when blood is spilled
How does retraction/contraction of a clot occur?
-As platelets die they clind to the fibrin filaments and pull by their actin-myosin system
What is the purpose of retraction/contraction?
- Toughen the clot by squeezing out fluid
- Pull together the sides of small wounds
What is the difference between anticoagulants and fibrinolysis?
- Anticoagulants oppose the formation of fibrin
- Fibrinolysis destroys the fibrin clot after it has been formed
Name some natural anticoagulants
- Protein C
- Protein S
- Antithrombin III
What happens if you lack some of the body’s natural anticoagulants?
-repeated episodes of thrombosis
What is the purpose of the fibrinolytic system?
-Break down fibrin
What is the active molecule which breaks down fibrin?
-Plasmin
How is plasmin activated?
-From the inactive precursor plaminogen by plasminogen activators such as tPA and urokinase
What is streptokinase?
-A therapeutic plasmonigen activator obtained from streptococci
When are plasminogen activators used therapeutically?
- To dissovle fibrin and thus thrombi/thromboemboli
- To attack fibrinogen to cause a general depletion
Why is recombinant tPA better to use than streptokinase?
-Streptokinase is antigenic, tPA isnt
What happens to a vessel wall when it is severed?
-It constricts to limit blood loss and trap platelets
What factors do vessel endothelia possess which favours clotting?
- Produces von willebrand factor for platelet adhesion
- Favours the coagulation cascage
- Opposes fibrinolysis
What antithrombotic properties do vessel endothelia secrete?
- Plasminogen activators
- Prostacyclin (inhibits platelet aggregation)
- NO
- Thrombomodulin (opposes thrombin)
What is a thrombus?
-A clot which has formed inappropriately in the heart or vessels, from the constituents of blood, during life
What are the three fundamental predisposing factors to thrombosis?
Hint: Virchows triad
- Changes in the vascular wall (endothelial damage)
- Changes in blood flow (slow or tubrulent flow)
- Changes in blood (hypercoagulability)
Are all three of virchows triad necessary for a clot?
-No, it can be a combination of 2
How does endothelial damage predispose to thrombosis?
-Platelet exposure to von willebrand factor/Factor VIII complex
Provide examples of causes of endothelial damage
- Direct trauma
- Inflammation
- Surgery
- Atherosclerotic plaques which rupture
Why isn’t endothelial damage enough to cause a clot in arteries?
-The platelet thrombi do not grow due to swift current washing away the platelets and chemical mediators
Why does sluggish/turbulent flow predispose to thrombus?
-Plateslets have a higher chance of sticking to clotting factors and accumulating
Why does post-partum increase the chances of thrombosis in the lower limbs?
- Stasis of blood due to pressure on large veins of the pelvis
- Blood is hypercoagulable
In what situations is blood hypercoagulable?
- Pregnancy
- Post-operatively
- Smoking
Why is thrombus formation more frequent in veins?
-They have slower flow and the valves produce pockets of stagnant blood
How are lines of zahn formed?
-White platelet layer produces fibrin
-Fibrin traps RBCs producing red layer
-Surface of this layer is thrombogenic as platelets stick to it
-A second white layer of platelets forms
Process continues
Do clots which form after death have lines of zahn?
-No
What is a parietal thrombus?
-Thrombus which restricts the lumen
What is an occlusive thrombus?
-Thrombus which fills and obsrtucts the lumen
What are the possible fates of a thrombi?
- Resolution (thrombus dissolved)
- Propagation
- Organisation
- Recanalisation
- Embolism
- Occlusion
What is propagation of a thrombus?
- Progressive spread and enlargement
- Distally in arteries
- Proximally in veins (can be very large by the time it reaches femoral vein)
What is organisation of a thrombus?
-A reparative process when there is ingrowth of fibroblasts and endothelial cells to produce a fibrous scar on the vessel wall
What is recanalisation of a thrombus?
-Channels are formed through the thrombus to re-establish bloodflow (usually not complete)
What is an embolism?
-The blockage of a blood vessel by solid, liquid or gas, at a site distant from its origin
Why are arterial thrombi often parietal?
-Fast flowing blood prevents occlusion
What is the function of haemostasis?
-To stop bleeding (haemorrhage)
Describe the appearance of arterial thrombi
- Pale
- Granular
- Lines of zahn
- Low cell content
Describe the appearance of a venous thrombus
- Soft
- Gelatinous
- Deep red due high cell content
Why does a venous thrombi cause a pulmonary embolism?
- Part of thrombus breaks off and travels towards the heart
- In doing so the emboli grows in size as it passes through the large, slow-flowing veins
- In the heart it is pumped from the RV into the lungs where it causes obsrtuction due to the small vessels
How is DVT treated?
-Initially with intravenous heparin and oral warfarin to prevent propagation
What is the cause of a massive PE?
- Large emboli becoming lodges in the bifurcation of the pulmonary artery (saddle emboli)
- Ususally fatal
Where do most of the thrombi, which cause a PE arise?
-Popliteal vein of deep veins of the thigh (femoral/iliac)
What is the consequence of recurrent minor PEs?
-Pulmonary hypertension
What are the consequences of an arterial thrombus?
-Ischaemia or infarction dependant on site and collateral circulation
What are the possible consequences of venous thrombi?
-Congestion, oedema, ischeamia and infarction
What are possible types of emboli?
- Thrombo-emboli
- Air (syringe)
- Amniotic fluid
- Nitrogen (divers, the bends)
- Medical equiptment
- Tumour cells
- Fat
What are the most likely places of embolism if the origin was the heart?
-Renal, mesenteric of hepatic arteries
How does an embolism get to the brain?
- From atheromatous carotid arteries
- From the auricles of the heart
Name some predisposing factors to DVT
-Immobility, bed rest, post-operative,pregnancy/post partum, oral contracemptives, severe burns, cardiac failure
How is DVT managed during surgery?
-High risk pateints identified and offered prophylaxis (leg compression stockings, heparin)
What is a latrogenic ebolism?
-When oily substance is injected into artery instead of vein
When can fat embolism occur in the lung?
-On inhalation of carbon
How can PEs be prevented?
-Putting an umberella-shaped filter in the inferior vena cava
How is asprin antithrombogenic?
- Irreversible acetylates an enzyme in platelets which is needed to produce thromboxane
- Decreased platelet aggeragtion
What is disseminated intravascular coagulation and when does it occur?
- A condition where blood clots throughout the circulation and clotting and haemorrhage occur as clotting factors are used up causing susceptibility to haemorrhage
- Complication of primary event which triggers clotting eg sepsis, sevee trauma, shock, tumour, snakebite
What are clinical signs of disseminated intravascular coagulation?
- Microvasculat thrombosis causing neurological impairment, gangrene of the skin, renal failure and respiratory distress
- Haemorrhage causing intracerebral bleeding, petechiae, haematuria, gi bleeding
Why is the left heart a common site of thrombus formation?
- Infarcts commonly affect the LV causing thrombosis in the ventricular cavity
- Vegetations are common on valves of the LH
- Atrial fibrilation results in decreased atrial contraction, dilation of the LA-> stagnantion of blood with thrombus resulting
What is a paradoxical embolism? How do these occur?
- An embolus which has arisen in the systemic veins but embolises in the systemic arteries
- Small emboli can pass through arterio-venous anastamoses in pulmonary circulation
- Latge emboli pass through defects in the septa of the heart durinf coughing/lifting/straining as RH pressure increases
How does an atheromatous embolism arise?
-Atherosclerotic plaque ruptures and necrotic material released into bloodstream
What is a transient ischaemic attack?
- Episodes if neurological dysfunction which appear suddenly, last minutes to hours, then disappear
- Often caused by atheroembolism in brain from carotid vessels of LH
How do fat or BM emboli usually occur?
- Following a bone fracture
- BM released from break and sucked in to torn vessels
Why is air embolism lethal?
-Bubbles gather in the right heart as a frothy mass which stops the circulation
Why does the bends occur?
- Underwater, the body tissues and blood become saturated with nitrogen at a high pressure
- If a diver resurfaces too quickly, dissolved nitrogen come out of solution and is released into the body causing a gas embolus
What are the symptoms of amniotic fluid elbolism?
-Sudden respiratory distress and collapse
