Haemostasis and thrombosis -2

Question 1

Oral anti coagulants - commonly used?

Answer 1

Warfarin

Question 2

Heparin - when are they taken?

Answer 2

Inhibits different parts of the coagulation cascade (activates anti-thrombin)
Does this indirectly (exerts its effects via anti-thrombin)
Given by continuous perfusion

Question 3

Low molecular weight heparin - properties and administration

Answer 3

Smaller molecule / purer form
Less variation in dose
Subcutaneous administration and renal excretion
Given once daily, weight adjusted dosing

Question 4

Warfarin - how is it taken? Speed of absorption? When are most of the effects seen?

Answer 4

Orally taken
Rapidly absorbed
Peak effect 3-4 days after starting and impact still seen 4-5 days after stopped taking

Question 5

Side effects of warfarin

Answer 5

Bleeding

Embryopathy

Question 6

What value is the dose based on?

Answer 6

International normalised ratio
Dose based on this value - value for normal patients will be 1.0 so for patients with value of 2.0-3.0 –> will take 2x or 3x as long for the blood to clot
Frequency of monitoring of patient (eg how often blood test must be taken) depends on INR stability

Question 7

When is INR measured? How does INR impact warfarin as a drug

Answer 7

Measured before surgery
Warfarin very inconvenient drug to be on –> especially in the long term
No single dose for every person
Each patient needs different amounts per day (genetically controlled)

Question 8

Warfarin - drug targets - what is it and how does it work ?

Answer 8

VKORK - drug target - VKOR is vitamin K reductase to convert oxidised VitK to reduced Vitk.
Warfarin inhibits the prouduction of reduced vitamin K which prevents the production of clotting factors
Reduced Vitamin K leads to the production of functional clotting factors

Question 9

Warfarin - metabolising enzyme - relevance in terms of personalisation

Answer 9

CYP2C9 - metbolising enzyme of warfarin –> many polymorphisms in this enzyme between individuals
Identification of polymorphisms between individuals allow to work out dose

Question 10

What determines the dose of warfarin that will be used?

Answer 10

Polymorphism in combination with VKORK gene type –> resistance to warfarin –> determines dose!

Question 11

Direct oral anti-coagulants –> advantages ?

Answer 11

Orally administered - no monitoring needed
Standard dosing so the same for everyone
No alcohol / food interactions
Short half life (therefore may work out more expensive)
Inhibit thrombin and clotting factor X
Action around 2/3 hours, half life 12 hours

Question 12

Specific DOAC (direct oral coagulants) reversal agents

Answer 12

May be needed if patient urgently requires surgery (to allow clotting)
Humanised monoclonal antibody, IV administered, widely available
Short half life

Question 13

DOACs - advantages vs warfarin

Answer 13

Rapid onset of action
Fixed dose
No food or alcohol interactions
Low potential for drug interactions 
No monitoring required

Question 14

DOACs - disadvantages vs warfarin

Answer 14

Renal elimination (may be an issue if patient has kidney problems)
No specific antidotes for Xa inhibition
Licensed for specific indications only 
Only recently introduced