Lecture - Blood (Faed Thrombosis 1)

Question 1

Thrombosis - general

1. What is a thrombus? Formation of…..
2. Is it physiological or pathological?
3. What process is it closely linked to a pathological extension of?
4. What’re the constituents of a thrombus? Variable amounts of what things?
5. Aetiology of thrombosis - what is Virchow’s triad? (aka, there are varying combinations of three factors that cause thrombosis - what are they?). Also explain what aspect of these three actually contributes to the pathological extension of homeostasis (aka a thrombus).
6. What are some common and important examples of the intiating factors in thromboses?
   - egs of endocardial injury
   - egs of arterial injry
   - inflammation affecting blood vessels
7. In the example of myocardial infarction, the endothelium survives but it is what?
   - where does stasis occur?
   - patients with MI have multiple risk factors for what?

Answer 1

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Question 2

Part of Virchow’s triad: Arterial blood flow - arteries

1. Loss of laminar flow
   - what flow results if you lose the laminar flow? What does this flow lead to? What does it activate and what does this have an impact on?
   - alteration of ______ in turbulent flow - what does this factor do?
2. There is are sites of turbulence that he mentioned and they have an increased risk for a______ and m_____ thrombosis (what does this mean?)
   - what’s an aortic aneurysm? how is this built up? Why is there no occlusion?
3. Problems arising from stasis:
   - what cell activation is promoted with low blood flow and hypoxic conditions? (aka stasis) and then what will come into contact with the vessel wall to build up the thrombus?
   - what does surgery, trauma and veins in the lower limb have to do with this?
4. Development of venous thrombosis
   - thrombosis is a dynamic process over time. So blood must flow past the developing thrombus for what?
   - is thrombus a clot? Why not? (test tube….)
   - does it propage considerable distances? Why?
   - what can happen to the fragemtns that break off?

Answer 2

3. All these surgery, trauma and veins will release activated coag factors and platelets being present in the circulation and these aren’t washed away or diluted blood flow and won’t be inactivated if the conc increases too rapidly. In surgery, since you’re lying still, the pressure on your calf muscles and lack of movement will promote stasis and that’ll probably lead to the accumulation of activated coagulation factors and activated platelets - small thrombi form and they may propagate. Remember that this happens in combination of endothelial injury and hypercoagubility
4. Okay so there is a developing thrombus since there was an injury site and the platets attached there.

Question 3

Virchow’s traid: Hypercoagubility

1. What does this refer to? Any alternation of…..
2. Often this is multifactorial - what sort of factors is it referring to?

Answer 3

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Question 4

Explain this table

Answer 4

Okay so in arterial thrombosis, you need an endothelial injury to begin the process of a thrombus because this injury will expose the vWF, collagen and TF that will promote the adhesion (and activation) of platelets. The turbulent blood flow will cause worsening of (or cause the) the endothelial injury and activation of adhesion receptors and this will lead to further platelet activation and they’ll impact on the endothelium. In turbulent blood flow, you’ll also have alteration of vWF which will bind to platelets and form platelet strings/clumps. The platelet activation might be partial intitally but may become irreversible.

In venous thrombosis, there will be endothelial injury to initiate the thrombosis development but mostly it’ls like you’ll have stasis which will lead to low BF and hypoxic environment which can start to attach and build up the thrombus (endothelial activation). The stasis will also let the platelets come into contact with the vessel wall and they aren’t washed away so you’ll get acculumulation of activated coag factors and platelets so small thrombi form and may propagate (since thrombi arent very adherent). Need changes in coagubility like having trauma or surgery which will lead to increased coagulation factors, perhaps, that travel and then with the stasis will attach leading to te thrombus and propagation of it.

Question 5

Consequences of thrombosis:

1. Arterial: ischaemia and infarction - when no ______ ______ exists

• In arterial thrombosis causing an infarction, what is a usual predisposing factor? Which triggers what? Formation of what? Extension of what therefore….
• what’s a mural thrombus and what may occur with it? (e_____) Risk for what then?
  2. Consequences of venous thrombosis: pulmonary embolus
• what does this look like? It’s a thrombotic embolus loged in p_____ a______
• go look at slide 18 to see the histology of it
• in the histology of it, what do the area of RBC rich looks like vs fibrin and platelets?
• what is the pulmonary embolus a common adverse effect after? Like, what leads to the venous thrombus causing this embolus

Answer 5

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Question 6

Consequence of venous thrombosis

1. Acute
   - you’ll get 2 local things - what are they? And why do you get each?
   - organisation of thrombosis occurs over months - this leads to something being lost, what is it? What sort of organisation is it talking about it?
   - p_____ embolism may occur but it varies from mild to fatal
2. Chronic
   - why do you get raised venous pressure?
   - so you get v_____ veins (dilated and tortous) since loss of valves
   - you get something around the ankles after minimal trauma - why does this happen?
   - you’ll also get two things that you get in acute - what are they?
3. Why may recurrent thrombosis occur? Often a combination of factors can be identififed but there’s some acquired and inherited t______ (three acquired)
   - receurrnt pulmonary embolism - if this happens, what do you eventually lose a lot of?

Answer 6

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Question 7

Thrombophilia

1. What is it? (Increased risk for what?)
2. What are some common thrombophilia risk factors for arterial thrombosis? (acquired) and what sort of things lead to atherosclerosis from this?
3. Arterial and venous thrombosis have 4 main causes that’re listed here - what are they roughly and why may they cause thrombophilia? (it’s very logical - think about haemostasis what can increase that basically)

Venous thrombosis (before was arterial too)

1. Three sort of things that can lead to this and you’ve dicussed them before in this lecture
2. Go read about VTE in people who take the oral contraceptive and explain the gist of it to a wall

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SO you discussed antiphospholipid syndrome as an acquired cause of thrombophilia - what may these antiphospholipid antibodies cause?

• antiphosphilipid syndrome and the pathogenesis of thrombosis: explain the gist of it but remember that not all antiphospholipid antibodies are pathogenic - the pateint’s history is important
• how would you diagnose the antiphospholipid syndrome?

Answer 7

So in the antiphospholipid syndrome, you’ll have the activation of platelets partly by tubulent blood flow and then you’ll get phospholipid exposed. The autoantibody enchances the activation by binding to the phosphilipid (they’ll react with the phosppholipids on activated platelets and trigger them to complete activation) and that results in thromboses and thrombocytopenia (probably because using up platelets).

Question 8

Heparin-induced thrombocytopenia

1. Alright, explain to me everything you gathered from slide 33
2. How do you diagnose it?
3. What is UFH?

Answer 8

1. Okay so heparin is important in activating antithrombin. Platelet factor 4 is contained in alpha granules and has anti-heprain effect so it promotes coagulation since it inhibits heparin so AT doesnt get activated. Platelet factor 4 is relased when platelets are acticated or partially activated.

In HIT syndrome, the antibody will bind to heprain+PF-4 and somehow that will lead to enchaced platelet activation so you get thromboses and thrombocytopenia. It’ll apparently activate platets, neutrophils and macrophages through Fc receptors:

“The tail of the antibody then binds to the FcγIIa receptor, a protein on the surface of the platelet. This results in platelet activation and the formation of platelet microparticles, which initiate the formation of blood clots; the platelet count falls as a result, leading to thrombocytopenia”

Okay so heparin + PF4 + antibody binds to some protein on surface of platelets and that’ll ccause enchanced activation and then formation of thrombi and then thrombocytopenia.

2. Diagnose like if you have falling platelet counts after starting heprain and there doesnt seem to be any cause for thrombocytopenia -happens if you’re treated with UFH (also known as heprain)
3. UFH is unfractioned heparin. This will bind to AT and increase activity x300 so you get immediate anticoagulation. It has a very short half life - approx 50mins. And just remember that till will increase APTT (since you’re promoting anticoagulation) and so you can monitor the heprain anticoagulant effect with APTT. When you have HIT, then stop UFH immediately and change to an alternative that doesn’t cross react with the antibody (like low molecular weight heprain)