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Haematology BL > Anticoagulant Drugs - BB > Flashcards

Anticoagulant Drugs - BB Flashcards

1
Q

Heparin - general

A

Polymer - glycosaminoglycan structure
- Molecules of varying chain lengths

Activates anti-thrombin III (ATIII) - a naturally occurring anticoagulant

Occurs naturally (found in mast cells)

Used as medication in 2 forms:
1 - Unfractioned - widely varying polymer chains
2 - Low molecular weight - smaller polymers only

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2
Q

Clotting factors that unfractioned heparin (UFH) inhibits:

A

VIA ATIII

  • thrombin (II)
  • XII (12)
  • XI (11)
  • IX (9)
  • Xa (10)
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3
Q

Administration of UFH

A

IV/ SC - acute onset

Highly variable response to a dose:

  • Because of binding to plasma proteins/ cells
  • Dose must be adjusted to reach target PTT
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4
Q

Clotting tests in UFH:

A
  1. Increased PTT (intrinsic pathway) - because affects many components of this pathway
  2. Increased Thrombin Time
  3. Can increase PT at high doses
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5
Q

Reversal agent for heparin (UFH)

A

Protamine

UFH - not as effective with LMWH

Binds heparin and neutralises the drug

Used in:

  1. heparin overdose
  2. Cardiac surgery - where very high dose is needed for heart-lung bypass
    - Quick reversal is needed at end of surgery
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6
Q

Uses of UFH:

A

Acute management:

- DVT/PE
- MI
- Stroke

Prophylaxis:
- For DVT in hospitalised patients (SC)

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7
Q

Side effects of UFH:

A
  • Bleeding/ thrombocytopenia (rare)
  • Osteoporosis (in long term use)
  • Elevated AST/ALT (mild)
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8
Q

Heparin and thrombocytopenia:

A

2 Types:

  1. Non-immune thrombocytopenia
    • mild 10-20% reduction in platelets
    • Due to direct suppressive effect on platelet production
  2. HIT - Heparin-Induced Thrombocytopenia
    - Immune mediated reaction
    - Immune complexes bind to PF4-Heparin complex
    - TII hypersensitivity reaction
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9
Q

HIT:

A

Heparin induced thrombocytopenia

Type II hypersensitivity

Immune complexes bind to PF4-Heparin complex and these can cause:

- Removal by splenic macrophages (reduced platelets)
- Platelet aggregation/activation (THROMBOSIS)
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10
Q

Presentation of HIT:

A

5-10 days after exposure to heparin (in 0.2-5% of heparin patients)

  1. Abrupt fall in platelets (>50%)
  2. Arterial/venus thrombosis (can develop ischaemic limb/DVT)
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11
Q

Diagnosis and management of HIT:

A

Presumptive Diagnosis: - in ptx on heparin with:

  • Significan drop in platelet count
  • Thrombosis formation

Definitive diagnosis:
- HIT antibody testing - (takes days to come back and you dont want to wait)

Management:

  • Give alternative drug treatment
    - Lepirudin or Bivalirudin (Direct thrombin inhibitors)
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12
Q

LMWH - effects

A

Only inhibits factor Xa (indirectly through activation of ATIII)
- Limited compared to UFH

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13
Q

LMWH - administration

A

(Enoxaparin)

Predictable dosing - no need to titrate (based on weight)
- Because of reduced binding to plasma proteins and cells

Given subcutaneously (SQ)

Lower incidence of HIT

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14
Q

Clotting tests in LMWH:

A
  • Will not affect thrombin time (unlike UFH)
  • PTT is not sensitive to changes in LMWH-dose-induced changes
    - Response curve is shallow - UFH’s is steep
  • Monitoring of LMWH done using Anti Xa Levels
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15
Q

Monitoring of LMWH:

A

Anti Xa levels used (not PTT like in UFH)

Ususally no monitoring is needed - EXCEPT in:

  • Obestiy
  • Renal failure
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16
Q

Anti-Xa Level:

A

Xa substrate linked to chromophore (which illuminates when substrate is split) is mixed with patient sample

  • Low Xa activity - small amount of substrate splitting and therefore small amount of illuminaiton
  • High Xa activity - lots of substrate splitting - therefore greater illumination

Illumination is converted into a number - called ANTI-Xa ACTIVITY

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17
Q

Factor Xa inhibitors:

A

Indirect:

  • LMWH
  • UFH

Direct:

  • Rivaroxaban
  • Apixaban
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18
Q

Direct factor Xa inhibitors:

A

Rivaroxaban

Apixaban

19
Q

Uses of Rivaroxaban and Apixaban

A

Used in AF as alternatives to warfarin

20
Q

Direct Factor Xa inhibitors (Rivaroxaban and Apixaban) - general

A
  • ORAL DRUGS (DOACs)
  • Do not require monitoring of PT/INR
  • Standard dosing
21
Q

Direct Factor Xa inhibitors (Rivaroxaban and Apixaban) - test changes

A

Can increase PT and PTT (factor Xa in both pathways)

Will not affect thrombin time

22
Q

Direct thrombin Inhibitors: (DTIs) - Name the drugs

A

Hirudin

Lepirudin

Bivalirudin

Desirudin

Argatroban

Dabigatran - Only oral (DOAC)

23
Q

Test changes in DTIs:

A

Prolonged PT, PTT, and thrombin time

- Thrombin activity common to all these tests

24
Q

What can cause prolonged thrombin times?

A
  1. Unfractionated heparin (ATIII)

2. Direct thrombin inhibitors (DTIs)

25
Q

Uses of DTIs:

A
  1. Patients with HIT - (stop heparin start DTI)
    - Hirudin, lepirudin, bivalirudin, desirudin, argatroban
    - PTT often monitored whilst being administered
  2. ACS/ Coronary interventions
    - Bivalirudin
  3. Atrial Fibrillation:
    - (Dabigatran) - Oral (alternative to warfarin)
    - Standard dosing doesn’t require PT/INR monitor
26
Q

Warfarin Mechanism of Action:

A

Antagonist to vitamin K (epoxide reductase inhibitor)
- Epoxide reductase reduces vitamin K so that it can be used to activate clotting factors

Reduces levels of vitamin K dependent clotting factors (II, VII, IX, X)

27
Q

Vitamin K in Clotting cascade:

A

Reduced vitamin K Forms Gla residues in clotting factors (Gamma-carboxylation)

  • Then becomes oxidated
  • Epoxidase Reductase - reduces vitamin K back to usable form
28
Q

Dietary sources of Vitamin K

A

Green leafy vegetables (K1 form)

  • Cabbage, kale, spinach
  • Egg yolk
  • Liver
29
Q

K2 form of vitamin K

A

Synthesised by GI bacteria

30
Q

Administration of warfarin:

A

Takes days to achieve effects - because time required for clotting factors to fall

Dose adjusted to reach target PT/INR (once a month check needed)

  - Because drugs effect varies with diet (vitamin K)
  - Antibiotics may also kill GI bacteria - dec vit K - Increasing INR
  - Some drugs interfere with the metabolism of warfarin
31
Q

Warfarin Blood tests:

A

PT/INR used to measure effect because:

 - factor VII - has shortest half-life and will fall the fastest
 - therefore extrinsic pathway is most sensitive

PTT will also be increased - but less sensitive to warfarin

Thrombin time will be normal

32
Q

Prothrombotic effects of warfarin:

A

Protein C is vitamin K dependent with a short half-life
- is an anti-clotting factor

Initial warfarin treatment leads to a transient protein C deficiency (pro-thrombotic)
- Brief - as other factors will fall shortly after

33
Q

Mitigating prothrombotic effects of warfarin:

A

Other drugs such as heparin are given anytime warfarin is started in clot disorders (DVT/PE)
- however this is less relevant as often heparin is used for acute onset anyway before prophylaxis is started (because of its immediate effect)

ATRIAL FIBRILLATION - EXCEPTION:

  • No active clots, just a risk of clots
  • warfarin is often started without heparin
  • brief increase in risk of clot is very low
34
Q

Anticoagulants in pregnancy:

A

Warfarin - crosses placenta (avoided in pregnancy) - especially in 1st trimester
- can cause Fetal Warfarin Syndrome - abnormal foetal development

Unfractionated heparin is often used in pregnancy as it does not cross the placenta

35
Q

Warfarin skin necrosis:

A

Rare complication of warfarin therapy

  1. Occurs in ptx with protein C defiiency
  2. Can also occur at high doses

Initial exposure to warfarin causes decreased protein C - resulting in skin thromboses

Large dark, purple skin lesions

36
Q

Warfarin uses:

A

Stroke prevention in ptx with atrial fibrillation

Mechanical heart valves

DVT/PE - treated with warfarin for at least a few months

37
Q

Chronic oral coagulation:

A

Indications are:

  • AF
  • Mechanical heart valve
  • Prior DVT/PE

Drugs used:

  • Warfarin:
    - Pros: oral drug, cheap
    - Cons: Monthly INR monitoring
  • NOACs/DOACs:
    - Rivaroxaban/ apixaban and Dabigatran
    - Pros: Consistant dosing - no INR monitoring
    - Cons: Expensive, cannot be used in certain patients
38
Q

DOACs:

A

2x direct factor Xa inhibitors:

  • Rivaroxaban
  • Apixaban

1x Direct thrombin inhibitor:
- Dabigatran

CANNOT BE USED IN PTX with:

  • Dialysis
  • Mechanical heart valves
39
Q

Reversal agents for rivaroxaban and apixaban

A

Andexanet alpha - inactive decoy that binds the drug

40
Q

Reversal agent for Dabigatran:

A

Idarucizumab - anti-dabigatran monoclonal antibody

41
Q

3 Thrombolytic drugs:

A

tPA

Streptokinase

Urokinase

(all 3 increase conversion of plasminogen into plasmin)

42
Q

Risks of thrombolytic agents:

A

MAJOR bleeding risk as they break down clotting factors as well as fibrin

43
Q

Reversal of warfarin:

A
  1. Fresh Frozen Plasma (FFP)
    • Corrects deficiencies in any clotting factor
    • PT/PTT will normalise after infusion
    • Used if severe bleeding and increased INR
  2. Vitamin K (oral or IV)
    • IV can cause anaphylaxis
    • Used if raised INR and no bleeding

INR 3-5 - hold warfarin
INR 5-9 - Hold warfarin, oral vitamin K
INR >9 - Consider IV vitamin K, FFP

Raised INR + Severe Bleeding - > Administed FFP

Haematology BL (14 decks)

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