Anticoagulants

Question 1

What are coagulation factors present in the blood as?

Answer 1

Zymogens

Question 2

What is an endogenous inactivator of clotting factors?

Answer 2

Antithrombin III

Question 3

What is an important cofactor in the coagulation cascade?

Answer 3

Calcium

Question 4

Type of heparin

Answer 4

• Unfractionated heparin
• Low molecular weight heparins e.g. dalteparin, enoxaparin

Question 5

Compare the administration of unfractionated heparin + LMWH

Answer 5

• UFH: IV bolus + infusion or s.c. For prophylaxis
• LMWH: s.c.

Question 6

What is the mechanism of action of unfractionated heparin?

Answer 6

• Binds to antithrombin III > confirmation change > increases activity of ATIII > Xa inhibiton
• to catalyse inhibition of thrombin, binding to ATIII and IIa is needed

Question 7

What is the mechanism of action of LMWH

Answer 7

• inhibition of factor Xa by enhancing ATIII activity
• no affect on thrombin

Question 8

Why does LMWH have no affect on thrombin?

Answer 8

It is too short so cannot bind to both IIa and ATIII

Question 9

What is the mechanism of action of fondaparinux?

Answer 9

inhibition of factor Xa by enchanting ATIII

Question 10

Compare the half life of unfractionated heparin + LMWH

Answer 10

• UH: 20 mins low dose, 2hrs high dose
• LMWH: 2+ hours

Question 11

Why is heparin not given orally?

Answer 11

Large negatively charged molecules > would have very poor GI absorption

Question 12

Uses of hepatitis + fondaparinux

Answer 12

• prevention of venous thromboembolism - DVT + PE
• ACS with dual anti platelet therapy

Question 13

What are adverse drug reactions of heparins?

Answer 13

• bruising + bleeding
• herparin induced thrombocytopenia (more likely in UFH)
• osteoporosis
• hyperkalameia (due to inhibition of aldosterone secretion)

Question 14

What is heparin induced thrombocytopenia?

Answer 14

• antibodies to heparin platelet factor 4 complex produced
• depletion of platelets
• paradoxically can lead to thrombosis as more platelets activated by damaged endothelium

Question 15

What are important drug drug interactions of heparins?

Answer 15

Other antithrombotic drugs
ACEi/ARBs
K+ sparing diuretics

Question 16

Outline heparins monitoring

Answer 16

• aPTT used to monitor UFH
• less monitoring for LMWH as more predictable in action

Question 17

Outline the reversal of heparins

Answer 17

protamine sulphate
- forms inactive complex with heparin
- heparin dissociates from ATIII
- greater effect with UFH than LMWH + no affect on fondaparinux

Question 18

Example of vitamin K antagonist

Answer 18

Warfarin

Question 19

What are the uses of warfarin?

Answer 19

• venous thromboembolism
• PE
• DVT + secondary prevention
• superficial vein thrombosis
• AF when DOAC not suitable
• pre cardio version
• in heart valve replacement

Question 20

What is the mechanism of action of warfarin?

Answer 20

• inhibits activation of vitamin K decent clotting factors II, VII, IX + X
• inhibits conversion of vitamin K to active reduced form

Question 21

What clotting factors are vitamin K dependent?

Answer 21

II
VII
XI
X

Question 22

What is the onset of action + half life of warfarin?

Answer 22

• delayed onset of action
• t_1/2 - 36-48 hours

Question 23

What are contraindication for warfain?

Answer 23

Crosses placenta so avoid in pregnancy (especially 1st trimester)

Question 24

What are adverse drug reactions of warfarin

Answer 24

• bleeding
• epistaxis
• spontaneous retroperitoneal bleeding

Question 25

Outline the reversal of warfarin

Answer 25

- vitamin K - prothrombin complex concentrate IV - stop warfarin

Question 26

What does a high and low INR mean?

Answer 26

High INR - more anti coagulate Low INR - less anti coagulated

Question 27

What are important drug drug interactions with warfarin?

Answer 27

- CYP2C9 inhibitor - other anticoagulants - phenytoin, barbiturates, rifampicin, St John’s warts: increase [plasma] - NSAIDs: both bind to albumin

Question 28

Examples of DOACs

Answer 28

Apixaban Edoxaban Rivaroxaban Dabigatran

Question 29

What are the uses of DOACs?

Answer 29

Indicated in most situations where warfarin used to be the only option

Question 30

What DOACs affect factor Xa and what is their mechanism of action?

Answer 30

- *Apixaban, Rivaroxaban, edoxaban* - **inhibtion free Xa and bound to ATIII** - do not directly effect thrombin

Question 31

What is the mechanism of action of dabigatran?

Answer 31

Competitive thrombin inhibition to both circulation and thrombus bound IIa

Question 32

What are adverse drug reactions of DOACs?

Answer 32

Bleeding Skin reactions

Question 33

What are important drug drug interactions of DOACs

Answer 33

- carbamazepine, phenytoin + barbiturates decrease [plasma] - Macrolides increase [plasma]

Question 34

What DOACs is most prescribed + why?

Answer 34

Apixaban Better side effect profile

Question 35

What antidotes are available for DOACs

Answer 35

- **andexanet alfa** - Apixaban + Rivaroxaban - **idarucizumab**: dabigatran

Question 36

When may warfarin be more appropriate than a. DOAC?

Answer 36

Patients with prosthetic valves Higher risk of GI bleeding Antiphospholipid syndrome

Question 37

What bleeding risk score is used in AF patients?

Answer 37

ORBIT score

Question 38

What factor is used in prothrombin time and why?

Answer 38

**Factor VII** Most sensitive to vitamin K deficiency

Question 39

Which DOAC is a direct thrombin inhibitor?

Answer 39

Dabigatran