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103 theme 2 > Thrombotic disorders > Flashcards

Thrombotic disorders Flashcards

1
Q

what is deep vein thrombosis

A

blood clot in deep veins (iliac, femoral, popliteal, tibial)
can become an embolism

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2
Q

what are thrombotic risk factors

A 
Post-operative, especially orthopaedic
Hospitalisation
Cancer
Pregnancy
OCP
Long-haul flights
Obesity
IV drug abuse
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3
Q

how do DVT’s present

A

Can be no symptoms at all – clinically silent
Unilateral calf swelling/ heat/ pain/ redness/ hardness
Differential diagnosis: cellulitis, Baker’s cyst, muscular pain

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4
Q

what can DVT be mistaken for

A

Differential diagnosis: cellulitis, Baker’s cyst, muscular pain

Potentially fatal if missed

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5
Q

what is a doppler ultrasound

A

Ultrasound transducer produces a real-time two dimensional image of soft tissue structure
Colour duplex shows velocity and direction of blood flow

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6
Q

how is a doppler ultrasound used for diagnose DVT

A

Veins are non-compressible by U/S probe
Investigation of choice
Colour duplex shows velocity and direction of blood flow

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7
Q

what used to diagnose DVT

A

Venogram done in past

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8
Q

how can a D-dimer test be used to diagnose DVT

A

D-dimers indicate activation of the clotting cascade
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 U/S scan to confirm DVT

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9
Q

What can a D dimer test be used for

A

Likelihood of having a DVT can be assessed using the Wells risk score and doing a D-dimer test

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10
Q

what is an above knee DVT

A

iliac, femoral or popliteal veins

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11
Q

How is an above knee DVT treated

A

Therapeutic anti-coagulation using sub-cut LMW heparin (such as tinzaparin or enoxaparin)
Dose of LMW heparin according to weight
No monitoring required (but can use anti-Xa assay)
Ensure adequate EGFR > 30ml/min
Otherwise use iv unfractionated heparin (APTR 2.0)

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12
Q

how can a patient be switched to oral warfarin (if heparin ineffective)

A

Load patient with oral warfarin for 3-5 days
Stop LMW heparin once INR > 2.0 for 2 days
Maintain INR between 2.0-3.0 (target 2.5)
Monitor INR every 3 weeks

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13
Q

what is a PE

A

Pulmonary embolism

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14
Q

what are symptoms of micro-emboli

A

asymptomatic

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15
Q

what are the classical symptoms of PE

A

pleuritic pain
dyspnoea
haemoptysis

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16
Q

What are the symptoms of massive PE

A

syncope, death

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17
Q

What are other symptoms of PE

A

Observed or expected, tachycardia, tachypnoea, hypotension

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18
Q

what should you do for 1st and 2nd DVT

A

1st DVT: anticoagulants for 6 months

2nd DVT/PE: lifelong anticoagulation

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19
Q

what is a CTPA scan

A 
CTPA scan (CT pulmonary angiogram)
used to investigate DVT
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20
Q

What is a V/Q scan

A

ventilation/perfusion radio-isotope scan used to diagnose PE
Limitation: underlying lung disease
Many scans are – hence rarely done

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21
Q

what do V/Q scans indicate

A

Underperfusion ~ V/Q mismatch

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22
Q

how can an ECG be used to diagnose PE

A

Sinus tachycardia
Atrial fibrillation
Right heart strain (RBBB)
Classic: SI, QIII, TIII (rare)

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23
Q

How can a CXR be used to diagnose PE

A

Usually normal
Linear atelectasis
Small effusions

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24
Q

What are the outcomes of PE

A

5% mortality rate despite treatment
4% develop pulmonary hypertension
Cause of death in 10-30% of in-patient post-mortems
Up to 60% have micro-emboli at post-mortem

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25
Q

how is massive PE treated

A 
Mx: thrombolysis with tPA (Alteplase)
Tissue plasminogen activator (fibrinolytic)
2-6% risk of serious bleeding
iv unfractionated heparin
Monitor with APTR
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26
Q

what can massive PE lead to

A

Signs of shock

hypotension, acute dyspnoea, collapse, syncope

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27
Q

how is standard PE treated

A

LMW heparin injections – e.g. tinzaparin
Warfarin (target INR 2.5) for 6 months
Consider underlying causes

28
Q

what is LMW heparin used for specifically

A 
is better if underlying cancer
IVC filters (inferior vena cava filter) for treating PE
29
Q

How can DOAC be used to treat PE

A 
Consider a DOAC as an alternative
Dabigatran po (direct thrombin inhibitor)
Rivaroxaban po (direct Xa inhibitor)
30
Q

What is a thrombophilia screen

A

Consider in young patients with spontaneous VTE

31
Q

what are inherited causes of thrombophilia

A 
Factor V Leiden (5% of people)
Deficiency of natural anticoagulants:
Anti-thrombin deficiency
Protein C deficiency
Protein S deficiency
32
Q

what are acquired causes of thrombophilia

A

Anti-phospholipid syndrome

Test for lupus anticoagulant (DRVVT) and anticardiolipin Abs

33
Q

what are anti thrombotics

A 
Warfarin
Heparin (Unfractionated heparin
LMW heparin)
Newer agents
Dabigatran – oral direct thrombin (factor IIa) inhibitor
Rivaroxaban, Apixaban – oral direct factor Xa inhibitors
Anti-platelet drugs
Fibrinolytic agents (thrombolytics)
34
Q

What is warfarin

A

Vitamin K antagonist
Prevents γ-carboxylation of factors II, VII, IX, X
Required for functional maturation of these factors

35
Q

what does warfarin do

A

Prolongs the extrinsic pathway (prothrombin time)
Monitored by the international normalised ratio (INR)Target INR usually 2.5 for DVT/PE and AF
Target 3.5 for recurrent VTE or metal heart valves

36
Q

what are the pharmaco-dynamics of warfarin

A

Warfarin can take > 3 days to achieve therapeutic levels
Warfarin also inhibits the natural anti-coagulants:
Protein C
Protein S

37
Q

how does warfarin interact with cytochrome P450

A

Enzyme inhibitors potentiate warfarin:

Enzyme inducers inhibit warfarin:

38
Q

how does warfarin interact with alcohol

A

Binge drinking tends to potentiate warfarin

Chronic alcoholism tends to inhibit warfarin

39
Q

what is warfarin control also affected by

A

Binding to albumin
Absorption of vitamin K from GI tract
Synthesis of vitamin K factor by liver
Hereditary resistance

40
Q

what are warfarin side effects

A

Teratogenic – therefore use LMW heparin in pregnancy
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

41
Q

what reverses warfarin

A

If life-threatening bleed, give activated prothrombin complex (e.g., Octaplex or Beriplex) which contains vitamin K dependent factors II, VII, IX and X
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

42
Q

what is the dose for activated prothrombin complex during life threatening bleed

A

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

43
Q

what is heparin

A

Mucopolysaccharide that works by potentiating anti-thrombin

44
Q

what does heparin do

A 
Irreversibly inactivates factor IIa (thrombin) and factor Xa
Administered parenterally (injected)
45
Q

what are the types of heparin

A

Two formulations of heparin:
Unfractionated heparin given by i.v. infusion
Low molecular weight heparin given as s.c. injections

46
Q

is heparin safe in pregnancy

A

Safe in pregnancy

47
Q

what is unfractionated heparin used for

A

Given i.v. with 5000U bolus and ~1000U/hour infusion
Monitored by APTT ratio (APTR) with target of 2.0 x normal
Safe in renal failure as unfractionated heparin is metabolised by the liver and not renally excreted
If bleeding, protamine sulphate can be partially reverse heparin

48
Q

why is unfractionated heparin not often used

A

Not often used due to inconvenience of administration

49
Q

what is a rare complication of heparin

A

Heparin-induced thrombocytopenia (or HIT)
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

50
Q

what is LMW heparin used for

A 
LMW heparin include:
Tinzaparin (Innohep) 
Enoxaparin (Clexane) 
Dalteparin (Fragmin)
Used for thromboprophylaxis for hospital in-patients:
Tinzaparin
Enoxaparin
51
Q

how is LMW heparin used

A

Very convenient due to once daily s.c. injections
Prescribed according to patient’s weight
Patient must have creatinine clearance of over 30ml/minute
Not usually monitored (but can use the anti-Xa assay to monitor)

52
Q

what are direct oral anti-coagulants

A

Developed as oral alternatives to warfarin

No monitoring required, flat dosing, good safety profile

53
Q

what are DOACs used for

A

Developed as oral alternatives to warfarin

No monitoring required, flat dosing, good safety profile

54
Q

what are the two types of DOACs

A 
direct thrombin (IIa) inhibitor, e.g. dabigatran
– direct factor Xa inhibitor, e.g. rivaroxaban, apixaban
55
Q

when shouldn’t DOACs be used

A

Trials show clinical non-inferiority of DOACs when compared to warfarin and LMW heparin for VTE and AF
Should not be used for cardiac valves as inferior to warfarin

56
Q

what is rivaroxaban

A

a direct factor Xa inhibitor

Causes irreversible anti-coagulation

57
Q

what are indications of rivaroxaban

A

Indications:
VTE prophylaxis
Used for treatment of DVTs and PEs
Stroke prevention in atrial fibrillation

58
Q

what are the doses of rivaroxaban

A

Dosing is 15mg bd for 3 weeks, then 20mg od
or 15mg od if CrCl is 15-50ml/min
Apixaban is alternative anti-Xa drug dosed bd
Less affected by renal function (safe above 15ml/min)

59
Q

what is dabigatran

A

a direct thrombin inhibitor

60
Q

what are indications of dabigatran

A

VTE prophylaxis
Used for treatment of DVTs and PEs
Stroke prevention in atrial fibrillation

61
Q

what are the doses of dabigatran

A

Treatment dose is 150mg bd
Prophylactic dose is 110mg bd
Confirm creatinine clearance > 30ml/min

Can be reversed by Praxbind (Idarucizumab)

62
Q

what are the types of anti platelet drugs

A

Aspirin – cyclo-oxygenase inhibitor
Clopidogrel – ADP receptor blocker
Dipyridamole – inhibits phosphodiesterase
Prostacyclin – stimulates adenylate cyclase
Glycoprotein IIb/IIIa inhibitors

63
Q

what are Glycoprotein IIb/IIIa inhibitors used in

A

Used in angioplasty procedures

64
Q

what are thrombolytic agents used for

A

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

65
Q

what are fibrinolytic agents

A

tPA, Alteplase

Also streptokinase and urokinase

66
Q

how are fibrinolytics used

A

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

Standardized dosage regimens, aim to use within 6 hours

67
Q

what are the risks of fibrinolytics

A

Beware of contra-indications to thrombolysis

Risk-benefit ratio = haemorrhage/thrombotic risk balance

103 theme 2 (7 decks)

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