2.4 Anticoagulants

Question 1

How does heparin work as an anticoagulant?

Answer 1

potentiates the formation of complexes between Antithrombin III and activated factors of the coagulation cascade leading to their inactivation.

Question 2

How does antithrombin III work

Answer 2

It forms a 1:1 complex with activated factors (thrombin, Xa, IXa, XIIa) via a reactive site

Question 3

How is heparin administered?

Answer 3

Parenteral (prophylaxis)

Iv infusion with or without bolus for therapy

Question 4

How is heparin cleared?

Answer 4

Saturable: (rapid) – heparin binds to receptors on endothelial cells and macrophages and is internalized, depolymerized and metabolized into smaller fragments

Non-saturable clearance (slow): Renal

Question 5

How do you monitor heparin therapy?

Answer 5

APTT - important due to the variability in protein binding and metabolism between individuals

Question 6

What are the complications of heparin therapy?

Answer 6

Bleeding 
Heparin induced thrombocytopenia 
Osteoporosis  
Transaminitis 
Hyperaldosteronism 
Hypersensitivity

Question 7

What factors does warfarin inhibit?

Answer 7

II (thrombin)
VII
IX
X

Question 8

How does warfarin work?

Answer 8

It blocks the regeneration of vitamin K which is needed for the addition of gamma-carboxyglutamine acid residues on factors II, VII, IX and X as well as protein C and Protein S

Question 9

How does warfarin work?

Answer 9

It blocks the regeneration of vitamin K which is needed for the addition of gamma-carboxyglutamine acid residues on factors II, VII, IX and X as well as protein C and Protein S

Question 10

How is warfarin metabolised and what are the effects of warfarin dependent on?

Answer 10

By CYP2C9

Effects are dependent on the T1/2 of the vitamin K dependent clotting factors in the blood

Question 11

What do you need to give with warfarin?

Answer 11

It has a delayed onset of anticoagulation effect so commence after a patient is on heparin or LMWH

Question 12

What will initially happen with warfarin treatment?

Answer 12

Initial hypercoaguable state due to the decreased level of protein C

Question 13

What are the important drug interactions of warfarin?

Answer 13

Displacement of warfarin from albumin binding sites (anticonvulsants)

Inhibition or acceleration of drug clearance (antibiotics, barbituates)

Reduced absorption (cholestyramine)

Question 14

What genetic polymorphisms affect warfarin?

Answer 14

CYP2C9 polymorphisms

Vitamin K epoxide reductase polymorphisms

Question 15

How do you monitor warfarin therapy?

Answer 15

Prothrombin Time

Question 16

What are the complications of warfarin therapy?

Answer 16

Haemorrhage

Warfarin induced skin necrosis

Question 17

What causes warfarin induced skin necrosis?

Answer 17

the initial decrease in protein C which results in paradoxical activation of coagulation, resulting in a hypercoagulable state and thrombosis. The blood clots interrupt the blood supply to the skin, causing necrosis

Question 18

How can you reverse warfarin therapy?

Answer 18

Cessation - 3-5 days
Prothrombin complex concentrate
Vitamin K infusion - complete reversal with 10 mg

Question 19

Where is the main action of LMWH?

Answer 19

Factor Xa

Question 20

Where is the main action of LMWH?

Answer 20

Factor Xa

Question 21

What is the advantage of LMWH?

Answer 21

less binding to plasma, platelet or endothelial derived proteins → more predictable response to weight adjusted dose than heparin

Question 22

What are the complication of LMWH?

Answer 22

Bleeding, especially in renal impairment

Thrombocytopenia: lower incidence if initial exposure to LMWH rather than heparin

LMWH cannot be recommended once heparin associated thrombocytopenia has occurred

Question 23

How can you reverse LMWH therapy?

Answer 23

50% reversal with use of protamine

Question 24

What drug is used when there is heparin associated thrombocytopenia?

Answer 24

Danaparoid - similar to LMWH (blocks Xa)

Question 25

What are the two direct thrombin inhibitros?

Answer 25

Hirudin and Bivalirudin

Question 26

What drugs inhibit Xa?

Answer 26

Rivaroxaban and Apixaban

Question 27

What are the two direct thrombin inhibitors?

Answer 27

Hirudin and Bivalirudin

Question 28

What drugs inhibit Xa?

Answer 28

Rivaroxaban, Apixaban and Aristotle

Question 29

How does Rivaroxaban and Apixaban work and what are they used for?

Answer 29

Inhibit Xa - works in the plasma and in the prothrombinase complex within the clot to which heparin cannot reach

used for post surgical prevention

Question 30

What is usually used in conjunction with anticoagulants?

Answer 30

Antiplatelet drugs such as aspirin