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Haematology & immunology > Thrombophilia Treatment Wk3 > Flashcards

Thrombophilia Treatment Wk3 Flashcards

1
Q

Venous Thromboembolism (VTE)

A

Deep vein thrombosis
Pulmonary embolism

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2
Q

Deep Vain Thrombosis

A

Leg veins
Axillary / sub-Flavian/ renal/ inferior vena cava

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3
Q

Risk factors for VTE

A

Age
Previous VTE
Malignancy
Immobility/paresis
Surgery/trauma
Serious illness
COC/HRT
Pregnancy/puerperium
FH of VTE
Inherited thrombophilia
Obesity
(Varicose veins) (smoking)

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4
Q

Signs & symptoms of DVT

A

Swelling
Pain/tenderness
Warmth
Redness
None at all

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5
Q

Acutely swollen painful leg differential diagnosis

A

Cellulitis
Baker’s cyst

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6
Q

Pulmonary embolism PE

A

-dyspnoea (short of breath)
-tachypnoea (rapid breathing)
-pleuritic chest pain (on inhalation)
-tachycardia (rapid heartbeat)
-cough
-haemoptysis
-circulatory collapse

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7
Q

Problem extent per 100,000

A

DVT = 100
PE = 50
I.e VTE 150

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8
Q

Case fatality

A

DVT 5%
PE 23%
I.e. overall case fatality of 10% = 15 deaths/100,000

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9
Q

The need for treatment Barrie and Jordan 1960

A
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10
Q

Treatment of patients with DVT pharmacological

A

Pre 2015 start ‘anticoagulation’ with heparin and warfarin = slows down clotting - allow fibrinolytic to ‘catch up’
Continue warfarin for 3-6 months

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11
Q

What is heparin?

A

Injectable anticoagulant
Unfractionated heparin (UFH)
Mixture of sulphated glycosaminoglycans of variable lengths and molecular weights from porcine intestinal mucosal
Short half-life
Continual IV infusion in inpatients
Cheap
Easily reversible
Monitored in lab aPTT

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12
Q

Low molecular weight heparin (LMWH)

A

Enzyme / chemical cleavage of UFH into 1/3 fragments
outpatient use
Once daily
Pre-filled syringe - weight related

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13
Q

Diagram

A
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14
Q

Low Molecular Weight Heparin (LMWH)

A

Give more predictable anticoagulant response than UFH
Dose calculated by body weight= given without monitoring or dose adjustment
Main source is Porcine intestinal mucosal. = world wide shortages during swine flu pandemic - synthetic alternatives are required

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15
Q

Warfarin

A

Oral anticoagulant used

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16
Q

How does warfarin work?

A

Oral
Inhibits synthesis of vitamin-k dependant clotting factors- II, VII, IX, & X, and anticoagulant proteins C & S from liver
Easily absorbed, several days for therapeutic effect
Paradoxical initial prothrombotic effect
Initial reduction of protein C levels. = more likely to cause thrombus
Co-administration of heparin important

17
Q

Problem?

A
18
Q

Ideal anticoagulant?

A

oral
a wide therapeutic index
predictable pharmacokinetics and dynamics negating the need for monitoring
a rapid onset of action
an antidote
minimal non-anticoagulant side-effects
minimal interactions with other drugs and food

19
Q

Warfarin not ideal

A

YES oral
a wide therapeutic index X
predictable pharmacokinetics and dynamics negating the need for monitoring X
a rapid onset of action X
YES an antidote
YES minimal non-anticoagulant side-effects
minimal interactions with other drugs and food X

20
Q

Coumarins - drug interactions

A
21
Q

INR’s last 7 years

A
22
Q

Direct Thrombin Inhibitors (DTI’s)

A

Oral
Fixed dose
Less restrictive for patients – no blood tests!
Licensed since April 2008 for use in UK for prevention of VTE in orthopaedic surgery
Now licensed for use in DVT and PE

23
Q

Alternatives to warfarin

A
24
Q

Ximelagatran withdrawn due to liver safety concerns

A
25
Q

Alternatives to Warfarin

A
26
Q

Direct oral Thrombin inhibitions (FII) Dabigatran

A

Dabigatran etexilate is metabolised rapidly by non-specific esterases in the blood to dabigatran
Peak levels 2 h post dose
Half-life 12 -17 h
80% renal excretion
Binds to and inhibits active Thrombin

27
Q

Direct oral Factor Xa inhibitors – Rivaroxaban

A

A small molecule which competitively and reversibly inhibits Xa, > 10000-fold greater selectivity than for other serine proteases.
Time to peak 2 - 4h
Terminal half-life 9h

28
Q

New anticoagulants versus warfarin side effects (Rel-risk)

A
29
Q

Effect on coagulants test

A
30
Q

When do u need to measure a ‘no need to monitor’ therapy

A

Thrombosis
Bleeding
Renal failure
Overdose
Emergency surgery

31
Q

Are direct thrombin inhibitors (DTI’s) good anticoagulants

A
32
Q

Historic reversal options

A

Haematology & immunology (11 decks)

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