Thrombophilia Treatment Wk3 Flashcards
Venous Thromboembolism (VTE)
Deep vein thrombosis
Pulmonary embolism
Deep Vain Thrombosis
Leg veins
Axillary / sub-Flavian/ renal/ inferior vena cava
Risk factors for VTE
Age
Previous VTE
Malignancy
Immobility/paresis
Surgery/trauma
Serious illness
COC/HRT
Pregnancy/puerperium
FH of VTE
Inherited thrombophilia
Obesity
(Varicose veins) (smoking)
Signs & symptoms of DVT
Swelling
Pain/tenderness
Warmth
Redness
None at all
Acutely swollen painful leg differential diagnosis
Cellulitis
Baker’s cyst
Pulmonary embolism PE
-dyspnoea (short of breath)
-tachypnoea (rapid breathing)
-pleuritic chest pain (on inhalation)
-tachycardia (rapid heartbeat)
-cough
-haemoptysis
-circulatory collapse
Problem extent per 100,000
DVT = 100
PE = 50
I.e VTE 150
Case fatality
DVT 5%
PE 23%
I.e. overall case fatality of 10% = 15 deaths/100,000
The need for treatment Barrie and Jordan 1960
Treatment of patients with DVT pharmacological
Pre 2015 start ‘anticoagulation’ with heparin and warfarin = slows down clotting - allow fibrinolytic to ‘catch up’
Continue warfarin for 3-6 months
What is heparin?
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
Low molecular weight heparin (LMWH)
Enzyme / chemical cleavage of UFH into 1/3 fragments
outpatient use
Once daily
Pre-filled syringe - weight related
Diagram
Low Molecular Weight Heparin (LMWH)
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
Warfarin
Oral anticoagulant used
How does warfarin work?
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
Problem?
Ideal anticoagulant?
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
Warfarin not ideal
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
Coumarins - drug interactions
INR’s last 7 years
Direct Thrombin Inhibitors (DTI’s)
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
Alternatives to warfarin
Ximelagatran withdrawn due to liver safety concerns
Alternatives to Warfarin
Direct oral Thrombin inhibitions (FII) Dabigatran
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
Direct oral Factor Xa inhibitors – Rivaroxaban
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
New anticoagulants versus warfarin side effects (Rel-risk)
Effect on coagulants test
When do u need to measure a ‘no need to monitor’ therapy
Thrombosis
Bleeding
Renal failure
Overdose
Emergency surgery
Are direct thrombin inhibitors (DTI’s) good anticoagulants
Historic reversal options
