Anti-coagulants

Question 1

When should anticoagulants be used

Answer 1

Anticoagulants should be used on lower platelet count venous thrombi to prevent venous thrombus formation and propagation

Question 2

Name some anticoagulants

Answer 2

Warfarin

Heparin

IIa and Xa inhibitors: fondaparinux, direct acting oral anticoagulants (DOACs) or NOACs (new OACs)

Question 3

How does warfarin work

Answer 3

Warfarin is a vitamin K antagonist which inhibts the production of Vit K dependent clotting factors

Warfarin prevents the conversion of Vit K to active, reduced form - Vit K becomes oxidised when it activates Vit K dependent factors

Question 4

Name the Vit K dependent clotting factors

Answer 4

Prothrombin (F II)

F VII

F IX

F X

Question 5

Describe the pharmacological properties of warfarin

Answer 5

Has good GI absorption

t1/2 of 36-48hrs

Has ~100% bioavailability when taken orally

Is highly protein bound

Takes a while to have an effect as there are circulating clotting factors in the blood that must be cleared before the effect of warfarin can be seen

Question 6

Name some uses of warfarin

Answer 6

DVT prophylaxis and treatment

PE prophylaxis and treatment

AF with high risk of stroke

Protein S and C deficiency

Following orthopaedic surgery

Question 7

Name some ADRs of warfarin

Answer 7

Bleeding

Difficult to manage for several weeks after being given

Is teratogenic in 1st trimester and causes brain haemorrhage in 3rd

Question 8

Name some DDIs of warfarin

Answer 8

Majority of warfarin DDI have anticoagulant action:

• Inhibition of hepatic metabolism - amiodarone, clopidogrel, quinolone, metronidazole, ethanol
• Inhibition of platelet function - aspirin
• Decreased vit K by killing gut bacteria - cephalosporins
• Displacement of warfarin from plasma albumin - NSAIDs

Some DDIs decrease the effect of warfarin:

• Acceleration of warfarin metabolism - barbiturates, phenytoin, rifampicin, St Johns Wort

Question 9

What is the INR target for patients being given warfarin

Answer 9

IRN target of 2.5 (+/- 0.5) for most cases

INR target of 3.5 (+/- 0.5) in other cases like receurrnet DVT or PE in pateints with receiving anticoagulation already. In patients with mechanical prosthetic valves

Question 10

Describe heparin and how it works

Answer 10

Heparin inhibts the action of coagulation factors and helpts to speed up the action of antithrombin

It is produced by mast cells and vascular endothelium

Heparin used is either unfractionated or low molecular weight

Question 11

Describe unfractionated heparin and how it is given

Answer 11

UFH t1/2 is around 30mins at low dose and 2hrs at high dose

UFH binds to ATIII causing conformational change and increased activity

Typically given as IV infusion or subcutaneously

Can be stopped while LMWH last longer and requires a reversal agent to stop it

Question 12

Describe low molecular weight heparin

Answer 12

LMWH is a smaller chained heparin that has a higher bioavailbility and a longer t1/2 (2hrs)

LMWH does not inactive thrombin as it is not long enough, however, it targets F Xa

Less monitoring required compared to UFH

Does not bind to endothelial cells, plasma proteins or macrophages so dose more predictable

Given subcutaneously and cleared by kidneys

Question 13

Name some UFH and some LMWH drugs used

Answer 13

UFH - heparin

LMWH - dalteparin, enoxaparin

Question 14

Name some uses of heparin

Answer 14

DVT, PE, AF - given prior to warfarin as it has a quicker onset

Acute coronary syndrome - reduces recurrence or extension of cornary artery thrombosis post MI and STEMI

During pregnancy

Prevent VTE

Question 15

Name some ADRs of heparin

Answer 15

Bruising and bleeding

Heparin induced thrombocytopenia - autoimmune response caused by antibodies being produced that destroy platelets

Osteoporosis - higher risk with UFH

Hypersensitivity

Question 16

What is used to reverse the use of heparin

Answer 16

Protamine sulphate is used as it dissociates heparin from ATIII by irreversible binding

Given IV or IV infusion

Used as an antidote to heparin when large dose of heparin used

Question 17

Describe fondaparinux

Answer 17

Fondaparinux is a synthetic pentasaccharide that selectively inhibts Xa by binding to ATIII

Given S.C. with t1/2 of 18hrs

Less monitoring than UFH

Question 18

Name two types of DAOCs/NOACs and some drugs within the types. When are they not used

Answer 18

Direct Xa - apixaban, eboxaban, rivaroxaban

Direct thrombin inhibitor - argatroban, dabigatran

Are not used following valve replacement as they have a high risk of clots after valve surgery

Question 19

Describe how direct Xa inhibitors work

Answer 19

Direct Xa inhibitors inhibt free Xa and Xa bound with ATIII

Does not effect thrombin

Given PO and cleared by hepatic metabolism

Has t1/2 of 10hrs

Question 20

Describe how direct thrombin inhibitors work

Answer 20

Direct thrombin inhibitors are selective direct competitive thrombin inhibition

They inhibit circulating and thrombus bound IIa active metabolites

Metabolites have t1/2 of 30-60mins

Given PO