Anticoagulant Drugs

Question 1

indications for anticoagulant drugs?

Answer 1

venous thrombosis
atrial fibrillation (causes stasis of blood in left atrium which can clot and cause embolism so like venous thrombosis)

Question 2

what di anticoagulant drugs target in general?

Answer 2

formation of fibrin clot

Question 3

cadioembolic vs atheroembolic stroke?

Answer 3

cardioembolic = clot from AF commonly, treated with anticoagulants
atheroembolic = due to atheroma in situ which ruptures, treat with anti platelets

Question 4

naturally occurring anticoagulants?

Answer 4

anti thrombin

protein C and S

Question 5

proteins C and S are dependant on what?

Answer 5

vitamin K

therefore affected by warfarin

Question 6

what is used in acute venous thrombosis (DVT, PE, acute Afib etc)?

Answer 6

anticoagulants prevent clot forming/getting bigger and embolising but don’t dissolve the clot
heparin usually used which potentiates antithrombin and has an immediate effect

Question 7

2 forms of heparin?

Answer 7

unfractionated

LMWH (most commonly used)

Question 8

how does heparin work?

Answer 8

joins the anti-thrombin and thrombin complex and potentiates the effect of the antithrombin by keeping them bound together
also binds to activated clotting factor 10 and prevents its action

Question 9

when is unfractionated heparin used?

Answer 9

can be used IV in few cases with complicated patients with history of bleeding
unfractioned heparin IV can be stopped and action stops very quickly

Question 10

how is heparin therapy monitored?

Answer 10

APPT (thrombin feeds back to activate factors 8 and 9) - mainly needed for unfractioned
anti Xa assay can be used for LMWH but LMWH usually doesn’t need to be monitored

Question 11

which does heparin prolong, APPT or PT?

Answer 11

both

APPT more sensitive however

Question 12

potential complications in heparin therapy?

Answer 12

mainly bleeding
can have heparin induced thrombocytopaenia with thrombosis (HITT) due to immune reaction with antibodies to the heparin and platelets
can get osteoporosis with long term use (alters osteoclast activity)

Question 13

how is heparin action reversed?

Answer 13

stop heparin (action reverses quickly in unfractioned but slower in LMWH)
can give antidote to heparin if needed
- protamine sulphate completely reverses antithrombin effect in unfractioned and partially in LMWH

Question 14

what drugs might be used for a few months after a venous thrombosis (DVT etc) to reduce risk of a clot or a stroke etc?

Answer 14

warfarin (mainly)

Question 15

warfarin mechanism?

Answer 15

inhibits vit K

Question 16

where is vit K absorbed and what is needed?

Answer 16

upper intestine

needs bile salts to be absorbed

Question 17

fat soluble vitamins?

Answer 17

A, D, E, K

Question 18

which clotting factors does vit K carboxylate in the liver?

Answer 18

2, 7, 9, 10

Question 19

what factors are dependant on vit K and will therefore become deficient without vit K?

Answer 19

protein C and S (decrease first)

factors 2, 7 9 and 10 (decrease a few days later)

Question 20

why must heparin be given with warfarin?

Answer 20

warfarin initially makes you more pro-thrombotic due to decrease in protein C and S

Question 21

action of vit K?

Answer 21

carboxylates glutamic acid residues in factors 2, 7, 9 and 10 as well as protein C and S
adds 1 of the 2 COOH groups essential for the clotting factor to bind through calcium to phospholipid

Question 22

why is the second COOH needed in clotting factors for them to work?

Answer 22

second COOH group strengthens the chemical bond between clotting factor and platelet to form fibrin clot

Question 23

problem with warfarin?

Answer 23

narrow therapeutic window due to metabolism

Question 24

metabolism of warfarin?

Answer 24

in the liver

Question 25

when is warfarin initiated rapidly?

Answer 25

acute thrombosis | done in hospital with heparin

Question 26

when is warfarin initiated slowly?

Answer 26

``` AF liver failure malnourished elderly done in the community doesn't always needs heparin?? ```

Question 27

when should warfarin be taken?

Answer 27

same time every day

Question 28

how is warfarin monitored?

Answer 28

INR | aim for 2 (2-3 can generally be accepted)

Question 29

major adverse effects of warfarin?

Answer 29

haemorrhage

Question 30

what might influence bleeding risk in warfarin?

Answer 30

intensity of anticoagulation concomitant clinical disorders concomitant use of other medications quality of management

Question 31

complications of mild bleeding?

Answer 31

skin bruising epistaxis haematuria

Question 32

complications of severe bleeding?

Answer 32

GI bleeds intracerebral bleeds significant anaemia

Question 33

how is warfarin action reversed?

Answer 33

omit a warfarin dose or two or reduce dose (If INR is a bit high and some bruising but nothing serious) > give oral vit K (if INR consistently high but no life-threatening bleeding) > give clotting factors (high INR and serious bleeding) > clinical and lab assessment of response

Question 34

how long does vit K take to work vs clotting factors?

Answer 34

vit K = 6 hrs | clotting factors = immediate

Question 35

other new anticoagulants?

Answer 35

oral direct thrombin inhibitors | oral Xa inhibitors

Question 36

what clotting factors are affected by warfarin

Answer 36

prothrombin VII IX X

Question 37

what do the new anticoagulants target?

Answer 37

thrombin (e.g dabigatran) or Xa (e.g endoxaban, rivaroxaban, apixaban) (Xa inhibitors preferred)

Question 38

additional effect of warfarin that new anticoagulants don't have?

Answer 38

also good for arterial thrombosis