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103 theme 2 > Thrombotic disorders > Flashcards

Thrombotic disorders Flashcards

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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
how is massive PE treated
``` Mx: thrombolysis with tPA (Alteplase) Tissue plasminogen activator (fibrinolytic) 2-6% risk of serious bleeding iv unfractionated heparin Monitor with APTR ```
26
what can massive PE lead to
Signs of shock | hypotension, acute dyspnoea, collapse, syncope
27
how is standard PE treated
LMW heparin injections – e.g. tinzaparin Warfarin (target INR 2.5) for 6 months Consider underlying causes
28
what is LMW heparin used for specifically
``` is better if underlying cancer IVC filters (inferior vena cava filter) for treating PE ```
29
How can DOAC be used to treat PE
``` Consider a DOAC as an alternative Dabigatran po (direct thrombin inhibitor) Rivaroxaban po (direct Xa inhibitor) ```
30
What is a thrombophilia screen
Consider in young patients with spontaneous VTE
31
what are inherited causes of thrombophilia
``` Factor V Leiden (5% of people) Deficiency of natural anticoagulants: Anti-thrombin deficiency Protein C deficiency Protein S deficiency ```
32
what are acquired causes of thrombophilia
Anti-phospholipid syndrome | Test for lupus anticoagulant (DRVVT) and anticardiolipin Abs
33
what are anti thrombotics
``` 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
What is warfarin
Vitamin K antagonist Prevents γ-carboxylation of factors II, VII, IX, X Required for functional maturation of these factors
35
what does warfarin do
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
what are the pharmaco-dynamics of warfarin
Warfarin can take > 3 days to achieve therapeutic levels Warfarin also inhibits the natural anti-coagulants: Protein C Protein S
37
how does warfarin interact with cytochrome P450
Enzyme inhibitors potentiate warfarin: | Enzyme inducers inhibit warfarin:
38
how does warfarin interact with alcohol
Binge drinking tends to potentiate warfarin | Chronic alcoholism tends to inhibit warfarin
39
what is warfarin control also affected by
Binding to albumin Absorption of vitamin K from GI tract Synthesis of vitamin K factor by liver Hereditary resistance
40
what are warfarin side effects
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
what reverses warfarin
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
what is the dose for activated prothrombin complex during life threatening bleed
Dose is 25-50 units per kg depending on INR level (usual dose 1500-3000 units Octaplex)
43
what is heparin
Mucopolysaccharide that works by potentiating anti-thrombin
44
what does heparin do
``` Irreversibly inactivates factor IIa (thrombin) and factor Xa Administered parenterally (injected) ```
45
what are the types of heparin
Two formulations of heparin: Unfractionated heparin given by i.v. infusion Low molecular weight heparin given as s.c. injections
46
is heparin safe in pregnancy
Safe in pregnancy
47
what is unfractionated heparin used for
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
why is unfractionated heparin not often used
Not often used due to inconvenience of administration
49
what is a rare complication of heparin
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
what is LMW heparin used for
``` LMW heparin include: Tinzaparin (Innohep) Enoxaparin (Clexane) Dalteparin (Fragmin) Used for thromboprophylaxis for hospital in-patients: Tinzaparin Enoxaparin ```
51
how is LMW heparin used
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
what are direct oral anti-coagulants
Developed as oral alternatives to warfarin | No monitoring required, flat dosing, good safety profile
53
what are DOACs used for
Developed as oral alternatives to warfarin | No monitoring required, flat dosing, good safety profile
54
what are the two types of DOACs
``` direct thrombin (IIa) inhibitor, e.g. dabigatran – direct factor Xa inhibitor, e.g. rivaroxaban, apixaban ```
55
when shouldn't DOACs be used
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
what is rivaroxaban
a direct factor Xa inhibitor | Causes irreversible anti-coagulation
57
what are indications of rivaroxaban
Indications: VTE prophylaxis Used for treatment of DVTs and PEs Stroke prevention in atrial fibrillation
58
what are the doses of rivaroxaban
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
what is dabigatran
a direct thrombin inhibitor
60
what are indications of dabigatran
VTE prophylaxis Used for treatment of DVTs and PEs Stroke prevention in atrial fibrillation
61
what are the doses of dabigatran
Treatment dose is 150mg bd Prophylactic dose is 110mg bd Confirm creatinine clearance > 30ml/min Can be reversed by Praxbind (Idarucizumab)
62
what are the types of anti platelet drugs
Aspirin – cyclo-oxygenase inhibitor Clopidogrel – ADP receptor blocker Dipyridamole – inhibits phosphodiesterase Prostacyclin – stimulates adenylate cyclase Glycoprotein IIb/IIIa inhibitors
63
what are Glycoprotein IIb/IIIa inhibitors used in
Used in angioplasty procedures
64
what are thrombolytic agents used for
used to lyse fresh thrombi (usually arterial) by converting plasminogen to plasmin
65
what are fibrinolytic agents
tPA, Alteplase | Also streptokinase and urokinase
66
how are fibrinolytics used
Administered systemically in acute MI, recent thrombotic stroke, major PE, or massive iliofemoral thrombosis Standardized dosage regimens, aim to use within 6 hours
67
what are the risks of fibrinolytics
Beware of contra-indications to thrombolysis | Risk-benefit ratio = haemorrhage/thrombotic risk balance

103 theme 2 (7 decks)

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