Platelets And Clotting

Question 1

What is warfarin’s main mechanism of action

Answer 1

Inhibition of vitamin K dependent clotting factors production
(Stops conversion of VitK to active reduced form)

Question 2

Which clotting factors are affected by warfarin?

Answer 2

II (prothrombin), VII, IX, X

Extrinsic pathway

Question 3

How long does warfarin take to have an effect

Answer 3

Days

Rate of platelet turnover dependent. High half life

Question 4

How is warfarin given?

Answer 4

Orally - good GI absorption

Question 5

How is warfarin’s slow onset ameliorated

Answer 5

Heparin used initially to cover the patient until warfarin takes effect

Question 6

Which anticoagulant is the preferred choice for long term use?

Answer 6

Warfarin

Question 7

Is warfarin protein bound?

Answer 7

Yes, heavily bound to albumin

Caution with drugs that will displace it

Question 8

Can warfarin cross the placenta

Answer 8

Yes - do not give in 1st trimester (teratogenic) or 3rd (brain haemorrhage)

Question 9

How is warfarin monitored?

Answer 9

Extrinsic pathway factors, prothrombin time

Question 10

How do other drugs affect warfarin?

Answer 10

Majority increase the effect, but some may decrease.

Check BNF

Question 11

Which drugs inhibit hepatic metabolism of warfarin?

Answer 11

Amiodarone, quinolone, metronidazole, cimetidine, alcohol

Question 12

Which drug inhibits platelet function?

Answer 12

Aspirin

Question 13

Which drug reduces vitamin K from gut bacteria?

Answer 13

Cephalosporin antibiotics

Question 14

Which drugs inhibit warfarin action?

Answer 14

Antiepileptics, rifampicin, St John’s wort

Question 15

When is warfarin used?

Answer 15

DVT, PE, Atrial fibrillation, mechanical prosthetic valve, cardiac thrombus

Question 16

What are the adverse effects of warfarin?

Answer 16

Bleeding, bruising, teratogenic

Question 17

What is the usual loading dose of warfarin?

Answer 17

10mg (when INR is about 1), 10, 5, maintenance dose

Question 18

How long is INR monitored in warfarin patients?

Answer 18

1-4 weeks

Question 19

How is warfarin reversed?

Answer 19

Stop giving warfarin, IV vitamin K (takes 2/3 days), prothrombin complex concentrate, fresh frozen plasma (both work faster)

Question 20

When is prothrombin complex concentrate/fresh frozen plasma indicated?

Answer 20

With major bleeding

Question 21

When is vitamin K indicated?

Answer 21

When INR is >8

Need to keep patient on heparin until effects wear off

Question 22

What is the main mechanism of heparin?

Answer 22

Activates anti-thrombin III

Question 23

What does ATIII do?

Answer 23

Deactivates factor Xa and IIa

Also IXa and possibly some others

Question 24

What are the two kinds of heparin given?

Answer 24

Unfractionated (usually IV), low molecular weight (usually subcutaneous)

Question 25

What is the difference between the two kinds of heparin?

Answer 25

Unfractionated heparin can deactivate both IIa and Xa (large enough to bind to it and ATIII at the same time), LMW heparin can only deactivate Xa

Question 26

What is the main advantage of using LMW heparin?

Answer 26

``` It is absorbed more uniformly highly bioavailable long half life does not require monitoring less likely to cause thrombocytopenia ```

Question 27

Where is LMW heparin cleared?

Answer 27

Renally - take care in patients with renal impairment (reduce dose)

Question 28

Can heparin be given orally?

Answer 28

No - poor GI absorption

Question 29

Is UF heparin predictable?

Answer 29

No - variable bioavailability and action

Question 30

What anticoagulant is given as prophylaxis in peri-operative patients?

Answer 30

LMW heparin at a low dose

Question 31

Is warfarin still given peri-operatively?

Answer 31

No - warfarin patients are given heparin instead, as it can be quickly stopped if bleeding occurs

Question 32

Which form of heparin is given to patients with DVT, PE, or atrial fibrillation?

Answer 32

LMW heparin to cover initial period of warfarin loading, unless fine control is required (can't monitor routinely)

Question 33

What is heparin alone given for?

Answer 33

Acute coronary syndromes - reduces recurrence/extension of coronary artery thrombosis, MI, unstable angina, pregnancy in place of warfarin (cautiously)

Question 34

What are the adverse effects of heparin?

Answer 34

Bruising/bleeding (intracranial, injection sites, GI loss, epistaxis) Thrombocytopenia (autoimmune, leads to platelet depletion, stop heparin and give hirudin) Osteoporosis

Question 35

How is heparinisation reversed?

Answer 35

Protamine sulphate - dissociates it from ATIII (Overdose can cause bleeding) Stop heparin Give protamine

Question 36

How does aspirin work as an antiplatelet?

Answer 36

COX-1 inhibition

Question 37

How does dipyridamole work as an antiplatelet?

Answer 37

Phosphodiesterase inhibition

Question 38

How does clopidogrel work as an antiplatelet?

Answer 38

ADP antagonist

Question 39

What is the series of platelet action?

Answer 39

Platelet adhesion > activation > aggregation

Question 40

What platelet stage do aspirin/NSAIDs inhibit?

Answer 40

Activation | Irreversibly inhibits COX-1

Question 41

What is the mechanism of action of Gp IIb/IIIa inhibitors?

Answer 41

Prevent platelet cross-linking by targeting GpIIb/IIIa

Question 42

What platelet stage do clopidogrel and dipyridamole inhibit?

Answer 42

Platelet aggregation