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Haematology > Anticoagulant Drugs > Flashcards

Anticoagulant Drugs Flashcards

1
Q

What are the 2 main groups of thrombotic events?

A
  • Arterial: coronary, cerebral, peripheral.

* Venous: DVT, PE

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2
Q

What are i) arterial ii) venous clots rich in?

A

i) Platelets.

ii) Fibrin.

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3
Q

What are the 2 indications for anticoagulant drugs?

A
  • Venous thrombosis.

* Atrial fibrillation.

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4
Q

What do anticoagulant drugs target?

A

The formation of fibrin clot.

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5
Q

What is NOT activated in the formation of a venous thrombosis?

A

Platelets

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6
Q

Describe a venous thrombosis.

A

Activates coagulation cascade – so rich in fibrin clot

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7
Q

Platelets are more involved in arterial thrombosis – they stick to damaged atherosclerotic plaque

A

T

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8
Q

What risk is it important to prevent in those with AF?

A

Stroke

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9
Q

Why is stroke more likely in someone with AF?

A

The atrium of the heart quivers, instead of contracting properly.
This results in blood stasis, and the formation of a fibrin-rich clot on the wall of the left atrium.
If this clot breaks off, it follows the path of least resistance through the left ventricle, up the aorta, into the carotid artery and eventually into the circulation of the brain where it causes a stroke.

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10
Q

What are the 2 main naturally occurring anticoagulants.

A
  1. Serine protease inhibitors e.g. antithrombin

2. Protein C and protein S

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11
Q

Describe serine protease inhibitors.

A

Antithrombin switches off haemostasis by binding to and inactivating thrombin.

This results in the switching off of:

a. conversion of fibrinogen to fibrin.
b. positive feedback action of thrombin on both VIII/IXa and V/Xa.

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12
Q

Describe the function of Protein C and protein S.

A

Switch off factors V and VIII.

Activated when thrombin binds to thrombomodulin and changes its function.

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13
Q

What is the mechanism of action of heparin?

A

It potentiates antithrombin

Usually, antithrombin binds to thrombin/clotting factor Xa to switch them off. Heparin just makes this complex more stable, potentiating the effects of antithrombin.

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14
Q

What is the onset of effect like in heparin?

A

IMMEDIATE

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15
Q

Via what route is heparin administered?

A

Parenterally – IV or SC

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16
Q

What are the 2 forms of heparin?

A
  • Unfractionated

* Low molecular weight (LMWH)

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17
Q

In terms of mechanism, what is the difference between unfractioned heparin and LMWH?

A

Unfractionated – greater inhibition of thrombin

LMWH – greater inhibition of Xa. (Think abbreviations go together - LMWH + Xa)

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18
Q

What is used to measure unfractioned heparin?

A

Activated partial thromboplastin time (APTT)

  • Generally want to get this to 1-1.5x normal to give a good anticoagulant effect
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19
Q

Is monitoring for LMWH needed? If so, what is used?

A

Not usually – due to its more predictable response (can give set dose depending on pt’s weight).

But if needed, and Anti-Xa assay can be used.

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20
Q

What is the main risk to worry about with heparin?

A

BLEEDING !!!

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21
Q

What is there a risk of developing, particularly with unfractionated heparin? Describe this.

A

Heparin induced thrombocytopenia (with thrombosis) – HITT

This is an immune reaction in which antibodies to one of the platelet factors is developed. It can result in catastrophic thrombosis.

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22
Q

How is HITT monitored for?

A

Monitor FBC in patients on heparin. (be worried if see platelet count drop by about half within 5-10d of starting heparin).

Give an alternative drug.

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23
Q

What is the main long term complication of long term use of heparin?

A

Osteoporosis

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24
Q

Why is heparin not generally used in the long term?

A

Needs to be injected, can cause osteoporosis with long term use

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25
Q

What works well if you need to reverse the effects of heparin?

A

Just stopping it – since it has immediate onset and offset.

Unfractionated heparin will be gone within half an hour.

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26
Q

What can be used in severe bleeding to reverse the effects of heparin?

A

Protamine sulphate.

Reverses antithrombin effect.

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27
Q

Does protamine sulphate work for both unfractioned and LMWH?

A

Yes – completely reverses unfractionated heparin, but only partial reversal for LMWH.

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28
Q

Give examples of coumarin anticoagulants.

A
  • Warfarin.
  • Phenindione.
  • Acenocoumarin.
  • Phenprocoumon.
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29
Q

What is the difference between coumarin anticoagulants and heparin?

A

Coumarin anticoagulants can be used longer term than heparin

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30
Q

What is the mechanism of action of coumarin anticoagulants?

A

Inhibition of vitamin K

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31
Q

What is vitamin K soluble in?

A

FAT

32
Q

Where is vitamin K absorbed?

A

Upper intestine

33
Q

What is required for the absorption of vitamin K from the upper intestine?

A

Bile salts

34
Q

In relation to haemostasis, what is vit K required for?

A

Final carboxylation of clotting factors II (prothrombin), VII, IX and X.

35
Q

What factors are dependant on vitamin K?

A

Factors II (prothrombin), VII, IX and X.

AS WELL AS protein C and protein S.

36
Q

Where are clotting factors synthesised?

A

By liver hepatocytes

37
Q

What do clotting factors required vitamin K for?

A

Final carboxylation – an essential step for function.

38
Q

What is the significance of the fact that protein C and protein S are also vitamin K dependent factors?

A

Warfarin is given to stop clotting factors working, and reduce the risk of thrombosis.
But it also stops protein C and S working. These are naturally occurring anticoagulants. Therefore, people will be more pro-thrombotic in the first few days of warfarin therapy. This should be managed with LMWH in the first week.

39
Q

Why, when people are put on warfarin, are they pro-thrombotic for the first few days?

A

Warfarin, as well as stopping clotting factors from working, it also stops protein C and protein S from working

These are naturally occurring anti-coagulants so the patient will be pro-thrombotic in the first few days

40
Q

Describe the action of vitamin K on clotting factors.

A

Causes carboxylation of glutamic acid residues in factors II, VII, IX and X (as well as Protein C and S).

This makes clotting factors more negatively charged, and able to bind to platelet phospholipid through calcium.

41
Q

What clotting factors does vitamin K carboxylate?

A

2, 7, 9 and 10

NOTE: also PC and PS

42
Q

What happens in vitamin K deficiency/warfarin therapy?

A

Without the second COOH group, the chemical bond is too weak for effective attachment by coag factor. This results in failure of efficient coagulation cascade.

43
Q

If you carboxylate something, what do you add?

A

COOH

44
Q

Explain how warfarin acts as an anticoagulant.

A

Blocks the ability of vitamin K to carboxylate the vitamin K dependent clotting factors, thereby reducing their coagulant activity.

45
Q

What are the 2 ways in which warfarin therapy can be initiated?

A

Rapidly:
For acute thrombosis in hospital (with heparin to cover initial drop in protein C and s).

Slow:
For AF in the community.

46
Q

What might you do to warfarin dose in someone with renal failure?

A

Half the dose.

47
Q

What is warfarin metabolised by?

A

In the liver by cytochrome p450 – the same enzyme which metabolises alcohol and lots of other drugs.

48
Q

Why does warfarin therapy need to be monitored?

A

Due to its narrow therapeutic window.

49
Q

When should doses of warfarin be taken?

A

At the same time every day (6pm recommended).

50
Q

What is warfarin monitored using?

A

INR

51
Q

What does INR stand for?

A

Internationalised normalised ratio

52
Q

What is INR based on?

A

Prothrombin time (PTRISI)

53
Q

How does warfarin affect the screening tests for fibrin clot formation?

A

It prolongs both PT and APTT since it affects factors II (prothrombin), VII, IX and X

But it will affect PT more since factor VII has a shorter half-life.

54
Q

What is the INR target?

A

2-3 - maximises anticoagulation while minimizing bleeding risk.

55
Q

What is INR?

A

A mathematical “correction” (of the PT ratio) for differences in the sensitivity of thromboplastin reagents.

56
Q

What does INR allow for?

A

Comparison of results between labs, and standardized reporting of the PT.

57
Q

What is the major adverse affect of warfarin?

A

BLEEDING !!!

58
Q

What is the major adverse affect of warfarin?

A

BLEEDING !!!

Note: warfarin has few side effects except for bleeding

59
Q

What factors may influence bleeding risk in a patient who is on warfarin?

A
  • Intensity of anticoagulation.
  • Concomitant clinical disorders.
  • Concomitant use of other medications.
  • BEWARE DRUG INTERACTIONS.
  • Quality of management.
60
Q

Why is it important to be aware of drug interactions in a patient on warfarin?

A

Lots of other drugs are metabolised by cypP450 (e.g. antibiotics, alcohol)

If pt is on one of these other drugs, there won’t be as much time for cypP450 to metabolise warfarin, so levels rise, and so does INR.

61
Q

What is the highest ever IRN we would allow? (KNOW THIS !!!)

A

3-4.5, only if really high thrombotic risk

62
Q

What mild bleeding complications might warfarin therapy be associated with?

A
  • Skin bruising.
  • Epistaxis.
  • Haematuria.
63
Q

What severe bleeding complications might warfarin therapy be associated with?

A
  • Gastro-intestinal.
  • Intracerebral.
  • Significant drop in Hb.
64
Q

What 2 things is the management of bleeding in warfarin therapy dependant on?

A
  • Severity of bleeding.

* INR.

65
Q

Outline the pathway for warfarin reversal.

A
  1. No action
  2. Omit warfarin doses
  3. Give oral vitamin K (if INR>8 but no serious bleed)
  4. Give factor concentrates
  5. Clinical + lab assessment of response
66
Q

What is the speed of action of i) vit K ii) clotting factors?

A

i) 6 hours

ii) immediate.

67
Q

In terms of mechanism of action, what are the 2 types of new anticoagulant?

A
  1. Oral direct thrombin inhibitors.

2. Oral Xa inhibitors (bind directly to and inactivate factor X).

68
Q

Name a thrombin inhibitor.

A
  • Dabigatran.
69
Q

Why are warfarin inhibitors not used so much?

A

They are renally excreted, and most people on anti-coagulants are older people with AF. Therefore, giving a drug which is excreted by the kidneys could be risky

70
Q

Give 2 examples of Xa inhibitors.

A
  • Rivaroxaban.

* Apixaban.

71
Q

What are the 2 types of new anticoagulants?

A
  • Direct thrombin inhibitors (dabigatran).

* Direct activated factor X inhibitors (rivaroxaban, apixaban).

72
Q

What are the advantages of using new anticoagulants?

A
  • Oral administration, and no monitoring required.
  • Less drug interactions.
  • Lower risk of bleeding than warfarin (1/500 vs 1/200).
73
Q

What is the major disadvantage of using a new anticoagulant as opposed to warfarin?

A

There is currently no specific antidote for reversal.

74
Q

When are new anticoagulants used?

A
  • Instead of LMWH as prophylaxis in elective hip and knee replacement.
  • For selected patients for stroke prevention in atrial fibrillation.
  • For treatment of DVT/PE.
75
Q

Heparin is monitored by APTT

A

T

76
Q

Warfarin is monitored by INR

A

T

Haematology (26 decks)

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