Anticogulants

Question 1

what are anticoagulants used for?

Answer 1

Prophylaxis and treatment of thromboembolism

Question 2

What are the main types of anticoagulants?

Answer 2

Vitamin K antagonists e.g. warfarin Inhibitors of thrombin - unfractionated heparin, LMW heparin- enoxaparin fondapurinux

Question 3

What is WARFARIN?

Answer 3

A COUMARIN derivative with similar structures to vitamin K Active orall

Question 4

How does it act?

Answer 4

It blocks vitamin K dependent gamma carboxylation of glutamate residues on residues on factors II, VII, IX and X resulting in the production of modified factors known as PIVKA- proteins in vitamin K absence

Question 5

What is the importance of the production of these modified factors?

Answer 5

They cannot bind calcium and therefore become INACTIVE IN COGULATION

Question 6

How long does warfarin take to take effect?

Answer 6

2-3 days to achieve full potential as inactive forms replace active

Question 7

How are the effects of warfarin monitored?

Answer 7

with the PROTHROMBIN TIME expressed as the INR - the international normalised ratio

Question 8

What is warfarin’s half life?

Answer 8

long around 40 hours, and it takes as long as 5 days for it to return to normal once stopped.

Question 9

How is warfarin metabolised?

Answer 9

By HEPATIC microsomal enzymes to INACTIVE 7-hydroxywarfarin

Question 10

What are the adverse effects of Warfarin?

Answer 10

HAEMORRHAGE - in overdose reverse with clotting factor concentrates of FFP If severe consider vitamin K DRUG INTERACTIONS- induce= barbiturates, carbamazepine inhibit= ethanol, metronidazole TERATOGENICITY -

Question 11

What is heparin?

Answer 11

A naturally occurring GLYCOAMINOGLYCAN of VARYING MOLECULAR WEIGHT 5000-15000

Question 12

How is heparin given? is it long or short acting?

Answer 12

injection subcutaneously or iv short acting

Question 13

How does thrombin work?

Answer 13

It forms a 1:1 complex with ANTI THROMBIN III, a PROTEASE INHIBITOR that INACTIVATES THROMBIN (FACTOR II) when bound to heparin

Question 14

What also does the heparin- antithrombin II complex inhibit?

Answer 14

FACTOR Xa Factor IX so no formation of factor VIII

Question 15

How do you measure the effects of heparin?

Answer 15

By the ACTIVATED PARTIAL THROMBOPLASTIN TIME (APTT)

Question 16

Does heparin have a short or long duration?

Answer 16

Short, 4-6 hours

Question 17

What does LMWH-antithrombin III complex inhibit?

Answer 17

only factor Xa-> LESS BLEEDING

Question 18

Do LMWHs have a longer or shorter half life?

Answer 18

Longer half life therefore only requires SINGLE DAILY DOSES Prophylaxis doses don’t require monitoring

Question 19

What are the adverse effects of heparin?

Answer 19

HAEMORRHAGE LESS with LMWH than HEPARIN Bleeding from heparin normally controlled by stopping its administration but in severe cases PROTAMINE SULPHATE ( a basic peptide that combines with the acidic heparin) maybe required ALLERGIC RXN HEPARIN INDUCED THROMBOCYTOPENIA - HIT OSTEOPOROSIS THROMBOSIS- rare

Question 20

What is fondaparinux?

Answer 20

A PENTASACCHARIDE that inhibits factor Xa

Question 21

What has fondaparinux been shown to do?

Answer 21

Reduce VENOUS THROMBOEMBOLISM more effectively than LMWH in knee and hip arthroplasty and hip fractures given 6h post surgery or 12h after removal of epidural catheter

Question 22

What is Melagatran?

Answer 22

a newer DIRECT ORAL THROMBIN INHIBITOR

Question 23

What Advantages does Melagatran have over warfarin?

Answer 23

wide therapeutic and safety window no monitoring required no interactions with other medication

Question 24

What would the APTT and PT values do in a patient with Haemophilia A?

Answer 24

• APTT- activated partial thromboplastin time- instrinic pathway
• PT- prothrombin time= extrinsic pathway
• Factor VIII deficiency so APTT Increase , PT same

Question 25

How would the APTT and PT change with warfarin, dic or factor V or X deficiency?

Answer 25

• Prolonged APTT and PT
• both extrinsic and intrinsic effected

Question 26

How would the APTT and PT change with Von willebrand’s disease ?

Answer 26

• Deficiency in von willebrand factor a multimeric protein that is required for platelet adhesion.
• VWf is bound to factor VIII so -> reduction in factor VIII increase APTT normal PT

Question 27

What would give a increased PT and a normal APTT?

Answer 27

• Chronic liver disease