Anti-coagulants

Question 1

What activates the instrinsic pathway?

Answer 1

Exposed collagen

Question 2

What activates the extrinsic pathway?

Answer 2

Tissue factor

Question 3

Summarise the clotting cascade

Answer 3

1. Extrinsic and intrinsic pathway activate factor X->Xa
2. This activates prothrombin to thrombin
3. This activates fibrinogen to fibrin and forms a clot

Question 4

What electrolyte is important in the clotting cascade?

Answer 4

Calcium

Question 5

How is unfractionated heparin given?

Answer 5

IV bolus/infusion

SC for prophylaxis as it gives a much lower bioavailiability

Question 6

What is unfractionated heparin mechanism of action?

Answer 6

1. Binds to ATIII and causes a conformational change, increasing activity of ATIII

Question 7

How does unfractionated heparin inhibit thrombin?

Answer 7

It needs to bind simultaneously to ATIII and IIa

Question 8

How does unfractionated heparin inhibit factor Xa

Answer 8

It only needs to bind to ATIII

Question 9

Name two LMWH’s

Answer 9

Dalteparin, enoxaparin

Question 10

How is LMWH given?

Answer 10

Subcutaneously

Question 11

How does LMWH work?

Answer 11

It bind to ATIII and inhibits factor Xa only

Question 12

How does fondaparinux work?

Answer 12

It is a synthetic polysaccharide which selectively inhibits Xa by binding to ATIII. Given subcutaneously, t1/2 is 18 hours.

Question 13

Why does UFH need more monitoring?

How do you monitor it?

Answer 13

The dose response is non linear with variable bioavailability. It is monitored by looking at aPTT.

Question 14

Which heparin do you use in renal impairment?

Answer 14

UFH

Question 15

Which heparin do you use if you need fine control?

Answer 15

UFH

Question 16

Which heparin has a longer half life?

Answer 16

LMWH

Question 17

What are some ADR’s related to heparin?

Answer 17

1. Bruising and bleeding - intracranial, GI, epistaxis
2. Heparin induced thrombocytopenia - Antibodies to heparin platelet factor 4 complex. Platelets deplete but can lead to thrombosis as more platelets activated by damaged endothelium.
3. Hyperkalaemia - Aldosterone inhibited
4. Osteoporosis

Question 18

What is protamine sulfate?

Answer 18

It forms an inactivate complex with heparin, given IV.

It dissociated heparin from ATIII and causes irreversible binding.

Question 19

How does warfarin work?

Answer 19

Inhibits activation of vitamin K dependent clotting factors. Hepatic synthesis of 2, 7, 9 ,10

Question 20

Does warfarin work straight away?

Answer 20

No - takes a while as circulated active clotting factors have be used up and takes several days.

Question 21

What is the half life of warfarin?

Answer 21

36-48hrs

Question 22

Can you give warfarin in pregnancy?

Answer 22

No. Avoid in 1st trimester (teratogenic) and 3rd trimester (haemorrhage).

Question 23

What are some ADR’s of warfarin?

Answer 23

1. Bleeding

2. Epistaxis and spontaneous retroperitoneal bleeding

Question 24

What is a good antidote to warfarin?

Answer 24

Vitamin K
Prothrombin complex IV
Stop warfarin

Question 25

What is bridging therapy?

Answer 25

Giving LMWH when initiating or temporarily stopping warfarin (surgery, sickness)

Question 26

What are the warfarin DDI's

Answer 26

1. Any drug that interacts with enzyme inducers/inhibitors Amidodarone, clopidogrel, high alcohol dose, quinolone, metronidazole, - cephalosporins (they reduce gut bacteria that inhibit vit K) - NSAID's - Displace warfarin from plasma albumin. Decreased gut absorption of vit K. Increase INR. - 'CRAPS' P450 inducers decrease INR.

Question 27

How do you monitor a patient on warfarin?

Answer 27

INR

Question 28

What is an ideal INR?

Answer 28

<1.1

Question 29

What is a target INR in patients with DVT, PE, AF?

Answer 29

INR 2-3

Question 30

What is a target INR in patients with recurrent DVT or PE?

Answer 30

3.0 - 3.5

Question 31

Name 3 DOAC's

Answer 31

Apixaban, edoxaban, rivaroxaban

Question 32

How do DOAC's work?

Answer 32

They inhibit free Xa and those bound to ATIII. Hepatic metabolism and slightly kidneys. Half life 10hrs.

Question 33

How does dabigatran work

Answer 33

A direct competitive thrombin inhibitor, both circulating and thrombus bound IIa.

Question 34

Do you need to monitor DOAC's?

Answer 34

No

Question 35

How are DOAC's given?

Answer 35

Orally

Question 36

What are some ADR's of DOAC's?

Answer 36

1. Bleeding, caution in GI bleed groups 2. Metabolism by many routes. Don't use dabigatran in low creatinine clearance. 3. Affects by CYP inhibitors/inducers. Plasma increased by macrolides. 4. Lower intracranial bleed risk than warfarin.

Question 37

Can you use DOAC's in pregnancy?

Answer 37

No

Question 38

Is there an antidote for DOAC's?

Answer 38

Yes, andexanet.

Question 39

When is warfarin used over a DOAC?

Answer 39

In renal failure, mechanical valves, if you need to measure compliance