Lecture - Blood (Faed Thrombosis 2)

Question 1

Just remind yourself how Protein C and S inhibit blood coagulation

Answer 1

Okay so from what I remember, you have thrombin binding to thrombomodulin (which is present on endothelium) and then protein C is activated to protein Ca (aPC) and then that will work together with its cofactor protein S to inhibit factors 5a and 8a

Question 2

Inherited thrombophilia

So from last lecture, you know that this is when you have an increased risk for thrombosis

1. What are some common vs uncommon inherited thrombophilia mutations?

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2. There is a factor __ ______ which 3% of European population have (not common in other populations), what is it?
   - what’s its inheritance?
   - what sort of mutation is it? (truncation, inversion etc)
   - what does it bind tightly to? This will lead to what? So how does this impact thromobosis?
   - how much of a risk factor is it for heterozygous state and homozygous state?
   - in gist: what does factor 5 leiden bind to and then how does it increase risk for venous thrombosis? Does it impact arterial thrombosis? (slide 9)
3. How do you test for Factor 5 Leiden?

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4. Prothrombin mutation
   - high or low risk for venous thrombosis?
   - what gene abnormality and what type of mutation?
   - what does this result in? So like, what’s gonna happen to venous thrombosis?

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5. Deficiency of antithrombin, protein C or S (all anti-coagulating factors)
   - what’s the pattern of inheritance?
   - are homozygous states mild or not?

Answer 2

4. So like, it’ll increase the thrombin concentration and you’ll get increased thrombin burst and then fibrin production is increased so platelet activation is increased so like, increase risk for venous thrombosis

Question 3

Clinical approach to assessing a pateint with a possible (deep) venous thrombosis:

1. What’s the clinical evaluation - what’s the basic things you’d want to ask and test?
2. Treat it with what? Why? What duration?
3. What is a long term consequences of DVT? What sort of symptoms?

Clinical Risk Score assessment for lower limb venous thrombosis

1. Is the diagnosis self-evident? So what do you use (plus two other things). Look at slide 21 for the thing you’d use and then slide 22 to see the research studies of it . What are the messages you took about the clinical evaluation of DVT?
   - when do you not need to do the d-dimer test since you know it’ll be positve?

Taking Clinical History: suspected venous thrombosis:

-what sort of questions would you want to ask?

Answer 3

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Question 4

Labratory evalulation of thrombophilia

1. What are the first line lab investigations?
2. Give a summary of all the points raised about D-dimers

Imaging evaluation of pateints with suspected thromobsis

1. Comfirmation of venous thrombosis from 2 types of imaging studies:
   - what’s the relaibility of each? Like which one is the gold standard. If it is gold standard then why is it not always used?
   - Since both are imperfect in some way, what should you stratify cases by?

Simplified strategy:

1. If you get high probability in the Wells clinical score, what should you use to confirm and check the extent of DVT? In this situaiton, will D-dimer be performed?
2. If you get moderate probability, what should you request? (if no other…..) and also one more sort of evaluation
3. If you get a low probability then what should you request? (if……). You should use ultrasound only if what? What happens if the symptoms persist?

Diagnosis of pulmonary embolus (PE)

1. Something present somewhere in the body means high risk for pulmonary emobli - what is it? Active treatment of what is needed to prevent more emboli?
2. What are other sources of the pulmonary emobolus?
3. What do you use to evaluate lungs? What scan? How does it work?

Further evaluation of thrombophilia:

1. When is the investigation of possible thrombophilia only appropriate?
2. What should you beware of?
3. What other antibody test can you do? (think back to what leads to thrombophilia)

Answer 4

2. So you can do the D-dimer test (which is also done for assessing risk of venous thrombosis but I guess having thrombophilia is a leading factor to venous thrombosis). The D-dimer concentration is increased after venous thrombosis and many other conditions (so you dont need to do it when you know that raised levels are present eg due to surgery, inflam, trauma, DIC etc). The D-dimer test will be of no use if any of these are present since you dont know if the positive test is present due to DVT or becuase of these conditions. If you get a normal D-dimer level then you more or less won’t have DVT. If you have a normal D-dimer level, you can’t have ‘high probablilty’ on the Wells score.

Question 5

Very briefly, what’s the pharmacologically based and other approaches to prevention and treatment of thrombosis?

Answer 5

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Question 6

Prevention and treatment of thrombosis:

Principles of treatment with anticoagulants

1. Prevent arterial or venous thrombosis if what?
   - what do you use it during? What level of anticlotting do you need to actually stop the clotting?
2. Treatment of thrombosis and embolism
   - prevents what?
   - removes something but limited scope exists of this. How is this different in arterial vs venous thrombi?
3. So the anticoagulant drugs are well established in the treatment and prevention of what and not as effective for preventing what?
4. So what is used to prevent arterial thrombosis?

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Using Heprain (UFH) as an anticoagulant:

1. Major thromboembolism treatment for what? How is this related to warfarin? How is it given?
2. You can give it prophylactically to prevent what? How is it given? Who is it given to?
3. What are the main risks of UFH?

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Low molecular weight heprain (LMWH) as anticoagulant:

1. What is this derived from?
2. It has reduced effect but it retains a certain effect that is the main action needed to stop further thromobses - what’re they?
3. Does it require lab monitoring? So who can it be used with? How is it given?

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Warfarin as aticoagulant:

1. How does it work?
2. Start warfarin with care and under what?
3. Why may it produce an increased thrombotic risk for ~3 days?
4. Slow i____ eg for atrial fibrillation
   - atrium not emptying because of what? = atrial fibrillation
   - where will the thrombus form then?
   - so if they embolise, what do you have a risk of?
5. So you start at lower dose level and increase it slowly so you have what?
6. When do you give fast induction? What else is required?
7. How do you test the warfarin effect? What’s te formula?
8. What’s the therapeutic range for warfarin?
9. Okay so what are the complications and problems with warfarin? There’s 4 main ones

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New oral anticoagulatants

-drugs that interact with the active enzyme site of coagulation factors eg d______ - it’s not used widely used as an alternative to warfarin

Answer 6

5. Slow reduction in coagulation factors and Protein C and S?

Question 7

Prevention and treatment of thrombosis

Using fibrinolysis to treat thrombosis

Fibrinolytic agents:

1. When are fibrinolytic agents usually only effective?
2. What are the two types of fibrolytic agents and:
   - what’re they made of?
   - cost?
   - where do both work? Slide 41
   - wha’s it used in?

Question 8

Prevention and treatment of thrombosis

Platelets and anti-platelet agents

-there are three, what are they? How do they work?

Answer 8

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