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103 Theme 2 - Blood > Thrombotic disorders > Flashcards

Thrombotic disorders Flashcards

1
Q

Complete the diagram

A
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2
Q

What is Virchow’s triad and what is it a risk for?

A

Deep vein thrombosis

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3
Q

Name 8 thrombotic risk factors

A

◦Post-operative, especially orthopaedic

◦Hospitalisation

◦Cancer

◦Pregnancy

◦Oral contraceptive pill

◦Long-haul flights

◦Obesity

◦i.v. drug abuse

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4
Q

What condition does this show?

A

Deep vein thrombosis

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5
Q

What are the symptoms of a DVT?

A

Can be no symptoms at all – clinically silent

Unilateral calf swelling/ heat/ pain/ redness/ hardness

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6
Q

What are the differential diagnoses for DVT?

A

Cellulitis, Baker’s cyst, muscular pain

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7
Q

What is the investigation of choice for a DVT and why?

A

Doppler ultrasound

Veins are non-compressible by U/S probe

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8
Q

How can you assess the likelihood of having a DVT?

A

The Wells risk score and doing a D-dimer test

Low Wells score and negative D-dimer test have a high negative predictive value (>99% NPV)

If high Wells score or positive D-dimer then proceed to U/S scan to confirm DVT

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9
Q

What is a d-dimer test?

A

D-dimers indicate activation of the clotting cascade

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10
Q

What 3 veins are classed as an above-knee DVT

A

Iliac, femoral or popliteal veins

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11
Q

What is the initial treatment for DVT?

A

Therapeutic anti-coagulation using sub-cut LMW heparin (such as tinzaparin or enoxaparin)

Dose of LMW heparin according to patient’s weight

No monitoring required (but can use anti-Xa assay)

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12
Q

When would you use IV unfractionated heparin?

A

Ensure adequate EGFR > 30ml/min

Otherwise use iv unfractionated heparin (APTR 2.0)

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13
Q

What drug do you load the DVT patient with after 3-5 days?

A

Oral warfarin

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14
Q

When do you stop initial heparin after a DVT?

A

Stop LMW heparin once INR > 2.0 for 2 days

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15
Q

How long are patients anticoagulated for after a DVT?

A

1st DVT: anticoagulated for 6 months

2nd DVT/PE: lifelong anticoagulation

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16
Q

In what range should the INR be maintained in post-DVT patients?

A

Maintain INR between 2.0-3.0 (target 2.5)

Monitor INR every 3 weeks

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17
Q

What type of pulmonary emobolism is asymptomatic?

A

Micro-emboli

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18
Q

What are the symptoms of a pulmonary embolism?

What signs would you fin on examination?

A

pleuritic pain

dyspnoea

haemoptysis

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19
Q

What are the symptoms of a massive PE?

A

syncope, death

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20
Q

What does this show?

A

Pulmonary embolism

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21
Q

What investigations would you do for a pulmonary embolism?

A

CTPA scan (CT pulmonary angiogram)

V/Q Scan (ventilation/perfusion radio-isotope scan)

ECG

CXR

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22
Q

What type of scan is this and what does it show?

A

CTPA scan (CT pulmonary angiogram)

Saddle embolus: pre & post-thrombolysis

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23
Q

What indicates a PE on a V/Q scan?

A

Underperfusion - V/Q mismatch

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24
Q

What type of scan is this and what does it show?

A

V/Q Scan (ventilation/perfusion radio-isotope scan)

PE

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25
Q

What is the main limitation of V/Q scans?

A

Underlying lung disease

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26
Q

What will an ECG show in a PE?

A

Sinus tachycardia

Atrial fibrillation

Right heart strain (RBBB)

Classic: SI, QIII, TIII (rare)

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27
Q

What will a chest x-ray of a PE patient look like?

A

Usually normal

Linear atelectasis

Small effusions

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28
Q

What is a leading cause of ‘preventable death’ in the Western world?

A

PE

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29
Q

What signs of shock will patients with a massive PE have?

A

hypotension, acute dyspnoea, collapse, syncope

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30
Q

What is the treatment for a massive PE?

A

Thrombolysis with tPA (Alteplase)

Tissue plasminogen activator (fibrinolytic)

IV unfractionated heparin

Monitor with APTR

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31
Q

What is the risk associated with tissue plasminogen activator?

A

2-6% risk of serious bleeding

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32
Q

What is the treatment for a standard PE?

A

LMW heparin injections – e.g. tinzaparin

Warfarin (target INR 2.5) for 6 months

Consider underlying causes

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33
Q

For treatment of standard PE, which anticoagulant is best for patients with cancer?

A

LMW heparin is better if underlying cancer

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34
Q

What is the alternative treatment for a standard PE?

A

Consider a DOAC as an alternative

  • Dabigatran po (direct thrombin inhibitor)
  • Rivaroxaban po (direct Xa inhibitor)
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35
Q

When would you consider a thrombophilia screen?

A

Consider in young patients with spontaneous DVT

36
Q

What are the inherited and acquired causes that a thrombophilia screening looks for?

A

Inherited causes:

Factor V Leiden (5% of people)

Deficiency of natural anticoagulants:

  • Anti-thrombin deficiency
  • Protein C deficiency
  • Protein S deficiency

Acquired causes:

Anti-phospholipid syndrome

  • Test for lupus anticoagulant (DRVVT) and anticardiolipin Abs
37
Q

Draw the coagulation cascade

A
38
Q

What are the 5 types of anti-thrombotics?

A

Warfarin

Heparin

◦Unfractionated heparin

◦Low molecular weight heparin

Newer agents

◦Dabigatran – oral direct thrombin (factor IIa) inhibitor

◦Rivaroxaban, Apixaban – oral direct factor Xa inhibitors

Anti-platelet drugs

Fibrinolytic agents (thrombolytics)

39
Q

How does warfarin work?

A

Vitamin K antagonist

Prevents γ-carboxylation of factors II, VII, IX, X

Required for functional maturation of these factors

40
Q

What affect does warfarin have on the prothrombin time and why?

A

Prolongs the extrinsic pathway (prothrombin time)

Monitored by the international normalised ratio (INR)

41
Q

What is the target INR for warfarin patients?

A

Target INR usually 2.5 for DVT/PE and AF

Target 3.5 for recurrent VTE or metal heart valves

42
Q

How long can warfarin take to reach theraputic levels?

A

>3 days

43
Q

What 2 natural anti-coagulants does warfarin also inhibit?

A

◦Protein C

◦Protein S

44
Q

What drug interactions occur with warfarin due to cytochrome P450?

Inhibitors

Inducers

A

Enzyme inhibitors potentiate warfarin:

Enzyme inducers inhibit warfarin:

45
Q

What are the affects of alcohol on warfarin?

A

◦Binge drinking tends to potentiate warfarin

◦Chronic alcoholism tends to inhibit warfarin

46
Q

What 4 things is warfarin control affected by?

A

◦Binding to albumin

◦Absorption of vitamin K from GI tract

◦Synthesis of vitamin K factor by liver

◦Hereditary resistance

47
Q

Which anticoagulant is teratogenic?

A

Warfarin

48
Q

What drug should be used in pregnancy instead of warfarin?

A

LMW heparin

49
Q

What are the 4 side-effects of warfarin?

A

Significant haemorrhage risk

  • Intra-cranial bleeds up to 1% per year
  • Increased risk in elderly and with higher INR target

Minor bleeding up to 20% per year

Skin necrosis

Alopecia

50
Q

How would you treat a life-threateing warfarin bleed?

A

Give activated prothrombin complex (e.g., Octaplex or Beriplex) which contains vitamin K dependent factors II, VII, IX and X

Dose is 25-50 units per kg depending on INR level (usual dose 1500-3000 units Octaplex)

Give vitamin K 2-10mg iv/po depending on INR level

Patient can become refractory to re-loading with warfarin

Fresh frozen plasma (FFP) can also be used but this is not optimised for warfarin reversal

51
Q

What is heparin and how does it work?

A

Mucopolysaccharide that works by potentiating anti-thrombin

Irreversibly inactivates factor IIa (thrombin) and factor Xa

52
Q

How is heparin administered?

A

Administered parenterally (injected)

53
Q

What are the 2 formations of heparin and how are they administered?

A

◦Unfractionated heparin given by i.v. infusion

◦Low molecular weight heparin given as s.c. injections

54
Q

Is heparin safe in pregnancy?

A

Yes

55
Q

What type of heparin is more commonly used?

A

LMW heparin is very convenient due to once daily s.c. injections

Unfractionated heparin not often used due to inconvenience of administration

56
Q

How is unfractionated heparin monitored and what is the target?

A

Monitored by APTT ratio (APTR) with target of 2.0 x normal

57
Q

What anticoagulant is safe in renal failure and why?

A

Unfractionated heparin is safe in renal failure as it is metabolised by the liver and not renally excreted

58
Q

How is a unfractionated heparin bleed treated?

A

If bleeding, protamine sulphate can be partially reverse heparin

59
Q

What is heparin-induced thrombocytopenia and how is it diagnosed?

A

Heparin-induced thrombocytopenia (or HIT) is a rare complication of heparin:

◦Suspect if platelet count falls on heparin

◦This is paradoxically a prothrombotic condition that can cause VTE

◦Diagnosis by doing a HIT screen and discontinuation of heparin

60
Q

What is LMW heparin prescribed according to?

A

Prescribed according to patient’s weight

61
Q

How is thromboprophylaxis for hospital in-patients treated?

A

LMW heparin

–3,500U or 4,500U Tinzaparin

–20 or 40mg Enoxaparin

62
Q

When does the dosing of rivaroxaban change from 15mg bd to 20mg od?

A

After 3 weeks

63
Q

Patients must have a creatinine clearance rate of what to use LMW heparin?

A

over 30ml/minute

64
Q

Does LMW heparin need monitoring?

A

No

65
Q

Name 3 formulas of LMW heparin

A
  • Tinzaparin (Innohep) 175U/kg
  • Enoxaparin (Clexane) 1.5mg/kg
  • Dalteparin (Fragmin)
66
Q

What is the minimum creatinine clearance for dabigatran?

A

> 30ml/min

67
Q

Why were direct oral anti-coagulants (DOACs) developed?

A

Developed as oral alternatives to warfarin

68
Q

What does DOACs stand for?

A

Direct oral anti-coagulants, DOACs

69
Q

What are the benefits of DOACs?

A

No monitoring required, flat dosing, good safety profile

Trials show clinical non-inferiority of DOACs when compared to warfarin and LMW heparin for VTE and AF

70
Q

When should DOACs not be used?

A

Should not be used for cardiac valves as inferior to warfarin

71
Q

What are the 2 classes of DOACs?

A

– direct thrombin (IIa) inhibitor, e.g. dabigatran

– direct factor Xa inhibitor, e.g. rivaroxaban, apixaban

72
Q

What is rivaroxaban and how does it work?

A

Rivaroxaban is a direct factor Xa inhibitor

Causes irreversible anti-coagulation

73
Q

What are the 3 indications for rivaroxaban?

A

◦VTE prophylaxis

◦Used for treatment of DVTs and PEs

◦Stroke prevention in atrial fibrillation

74
Q

What are the 5 antiplatelet drugs?

A

Aspirin – cyclo-oxygenase inhibitor

Clopidogrel – ADP receptor blocker

Dipyridamole – inhibits phosphodiesterase

Prostacyclin – stimulates adenylate cyclase

Glycoprotein IIb/IIIa inhibitors

75
Q

When would the dose of rivaroxaban remain at 15mg od?

A

In patients with creatinine clearance of◦15-50ml/min

76
Q

What is apixaban and when is it used?

A

Apixaban is alternative anti-Xa drug dosed bd

Less affected by renal function (safe above 15ml/min)

77
Q

What is dabigatran?

A

Dabigatran is a direct thrombin inhibitor

78
Q

What are the 3 contraindications for Dabigatran?

A

◦VTE prophylaxis

◦Used for treatment of DVTs and PEs

◦Stroke prevention in atrial fibrillation

79
Q

What is the treatment and prophylactic dose of dabigatran?

A

◦Treatment dose is 150mg bd

◦Prophylactic dose is 110mg bd

80
Q

How is dabigatran reversed?

A

Can be reversed by Praxbind (Idarucizumab)

81
Q

What are fibrinolytic agents?

A

Thrombolytic agents used to lyse fresh thrombi (usually arterial) by converting plasminogen to plasmin

82
Q

Which anti-platelet drug is used in angioplasty?

A

Glycoprotein IIb/IIIa inhibitors

83
Q

Name 3 fibrinolytic agents

A

Tissue Plasminogen Activator (tPA, Alteplase)

Also streptokinase and urokinase

84
Q

When are fibrinolytic agents used?

A

Administered systemically in acute MI, recent thrombotic stroke, major PE, or massive iliofemoral thrombosis

85
Q

What is the risk of fibrinolytic agents?

A

Beware of contra-indications to thrombolysis

Risk-benefit ratio = haemorrhage/thrombotic risk balance

103 Theme 2 - Blood (10 decks)

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