Anticoagulant drugs

Question 1

what does warfarin target

Answer 1

vitamin K synthesis

vit k needed to produce clotting factors 2,7,9 and 10

Question 2

what does heparin target

Answer 2

anti-thrombin - makes it stronger

Question 3

what are the indications for anticoagulant drugs

Answer 3

Venous thrombosis

Atrial fibrillation

(to prevent clot forming in the left atrium (which isn’t contracting properly leading to stasis and pooling of blood) and the clot could break off into LV through carotids to the brain causing stroke).

Question 4

treatment of cardioembolic strokes vs atheroembolic

Answer 4

cardioembolic - anticoagulants bc its coming from AF in the heart, pooling of blood and fibrin clot

atheroembolic - anti platelets, due to atheroma in situ

Question 5

what are the naturally occurring anticoagulants

Answer 5

Serine protease inhibitors - anti thrombin

Protein C (factor V)

Protein S (Factor VIII)

Question 6

what natural anticoagulants are vitamin K reliant

Answer 6

protein C

protein S

so warfarin immediately drops protein C and protein S levels increasing risk of thrombosis

Question 7

what does heparin do

Answer 7

has an immediate effect to increase the action of anti-thrombin

given IV or SC

IV = unfractionated (needs a lot of monitoring for right does).

SC= low molecular weight heparin (more predictable and given on a weight basis)

Question 8

how does heparin increase the effect of antithrombin

Answer 8

joins antithrombin and thrombin together and stabilises them

also joints antithrombin and factor X to prevent prothrombin being converted to thrombin

Question 9

when is unfractionated heparin used

Answer 9

complicated patients with thrombosis but also risk of bleeding

can stop it quickly as it has a v short half life

Question 10

what is the predominant target for LMWH vs unfractionated

Answer 10

LMWH - more factor Xa

Unfractionated -more thrombin

Question 11

which test is most sensitive for monitoring heparin

Answer 11

APTT - activated partial thromboplastin time

Thrombin feeds back to activate factors VIII and IX making this test more sensitive than prothrombin time

Question 12

complications of heparin

Answer 12

Bleeding

heparin induced thrombocytopenia (with thrombosis) antibodies to the heparin and platelets - platelets tend to aggregate

osteoporosis with long term use

Question 13

what to do if bleeding on heparin

Answer 13

stop heparin - v short half life

can give antidote to heparin - Promatine sulphate

complete reversal for unfractionated and partial for LMWH because it only reverses binding to thrombin not factor Xa

Question 14

what oral agents do you use if a patient needs long term anticoagulation

Answer 14

Warfarin

3-6 months for first venous thrombosis

if more than one event = lifelong

Question 15

How does warfarin work

Answer 15

inhibits vitamin K

used for carboxylation of clotting factors 2,7,9 and 10

also used for protein C and protein S (so when you first give warfarin you make risk of thrombosis worse)

Question 16

where are vitamin K dependent clotting factors made

Answer 16

Liver

Question 17

how is vit K absorbed

Answer 17

fat soluble vitamin (ADEK)

absorbed in proximal intestine

needs bile salts to be absorbed

Question 18

what is the action of vitamin K

Answer 18

carboxylation of glutamic acid residues in factors II, VII, IX and X and protein C and S

leads to synthesis of non-functional clotting factors

Question 19

why does heparin need to be prescribed with warfarin

Answer 19

because of the initial decrease in protein C and S so makes you more thrombotic

Question 20

when would you not need to give heparin with warfarin

Answer 20

if you start giving it v slowly so the decrease in protein C and S is not as rapid

has a narrow therapeutic window so need to monitor therapy

dose should be given at the same time every day

Question 21

how do you monitor warfarin

Answer 21

prothrombin time - most sensitive as factor VII has the shortest half life

will also effect X and IX so also prolongs APTT but not as much as PT

Question 22

what is the INR

Answer 22

score used for monitoring warfarin therapy

international normalised ration

a mathematical correction of normal PT and mean PT

Question 23

risk factors for bleeding on warfarin

Answer 23

intensity of coagulation
contaminant clinical disorders
contaminant use of other medicines
quality of management

Question 24

what is the INR which is aimed for in warfarin monitoring

Answer 24

2-3

Question 25

types of bleeding complication on warfarin

Answer 25

Mild

• skin bruising
• epitaxes
• haematuria

Severe

• gastro-intestinal
• intraverebral
• significant drop in Hb

Question 26

how do you reverse the action of warfarin in bleeding

Answer 26

No action - if INR is normal and mild bleeding

omit some doses - if INR high and some mild bleeding

if INR high and not going down - administer oral vitamin K (takes about 6 hours for INR to come back down)

If major severe bleeding - administer clotting factors

Question 27

why dont you give clotting factors immediately

Answer 27

risk of infection (blood product)

expensive

Question 28

how quickly do vitamin k and clotting factors work

Answer 28

vit K - 6 hours

clotting factors - immediate

Question 29

where do clotting factors bind to to form the fibrin clot

Answer 29

surface of platelets in the platelet plug

Question 30

what do new anticoagulants target

Answer 30

Thrombin inhibitors (dabigatran) - directly inhibits thrombin (not through antithrombin like heparin)

Xa inhibitors (edoxaban, rivaroxiban, apixaban) - oral and dont need as much monitoring

Question 31

why are new anticoagulants better

Answer 31

less monitoring

oral

less risk of bleeding

less drug interactions

dont effect protein C and S so can go straight onto them

Question 32

what are new anticoagulants used for

Answer 32

prophylaxis for hip and knee replacement surgery

used for treatment of DVT/PE

Introduced for stroke prevention in Atrial Fib