M103 T2 L7 Flashcards
What are the thrombotic risk factors?
Post-operative, especially orthopaedic Hospitalisation Cancer Pregnancy OCP Long-haul flights Obesity i.v. drug abuse
How does DVT present?
Can be no symptoms at all – clinically silent
Unilateral calf swelling/ heat/ pain/ redness/ hardness
Potentially fatal if missed
What is the function of a doppler ultrasound?
shows the flow / lack of flow in a blood vessel
What is the initial treatment for DVT?
Therapeutic anti-coagulation using sub-cut LMW heparin (such as tinzaparin or enoxaparin)
How is the initial treatment of DVT administered / calculated?
Dosing is according to patient’s weight
No monitoring is required
patient needs to have adequate renal function
What is the patient treated with for DVt if they have renal impairment?
anti-coagulate with i.v. unfractionated heparin instead (maintain APTT 1.5-2.0)
only if the creatinine clearance of the kidney is less than 30ml/min
How is the patient treated after the initial treatment for DVT?
Load patient with oral warfarin for 3-5 days
warfarin levels monitored with INR tests
Stop LMW heparin once INR > 2.0 for 2 days
the first clot would be treated for six months - 1st DVT (femoral or iliac) - 6 months’ warfarin
the second DVT/PE: lifelong warfarin
Maintain INR between 2.0-3.0 (target 2.5)
What are the classical symptoms of DVT?
pleuritic pain - pain on inspiration
dyspnoea - difficulty breathing
haemoptysis - coughing up blood
What are the severe symptoms of DVT?
syncope
death
What are other conditions DVT patients might have?
O/E
tachycardic
tachypnoeic
hypotension
What are some statistics for DVT?
5% mortality with treatment
Cause of death in 10-30% of in-patient post mortems
Up to 60% have micro-emboli at post mortem
What is the treatment for DVT?
LMW heparin injections (better for cancer patients)
warfarin for 6 months
no oral contraceptive pill if associated with
IVC filter
DOAC / NOAC
Which age group would you consider doing a thrombophilia screen and why?
Sometimes done in younger patients with VTE to check for inherited risk factors
What are inherited risk factors for DVT?
deficiencies of anti-thrombin, Protein C and S
Prothrombin gene variant
Factor V Leiden
What is the function of warfarin?
Vitamin K antagonist - prevents post-translational modification / γ-carboxylation of factors II, VII, IX, X
in so doing it prolongs the extrinsic pathway (which is tested by measuring the prothrombin time)
What are the target INRs for warfarin patients?
Target INR for warfarin patients usually 2.5 for DVT/PE and AF
Target 3.5 for recurrent VTE or metal heart valves
How does warfarin work?
inhibits vitamin k reductase
it’s metabolized by p450
it prevents the formation of factors II, VII, IX, X
Why does it take warfarin a few days to work?
the different factors (II, VII, IX, X) have different half lives
so it takes 3-5 days to reach adequate levels of anti-coagulation for patients started on warfarin
Which four factors does warfarin affect?
II
VII
IX
X
How does warfarin affect the patient outside of the treatment?
warfarin also inhibits the formation of natural coagulants - protein C and protein S
bc these have very short half lives, when patients are started on warfarin they become pro-thrombotic before they become anti-coagulated bc their anti-coagulants are being depleted
Fall in protein C and S occurs within hours and can result in a temporary pro-coagulant state
How is warfarin prescribed?
Patient usually loaded with more warfarin then they need
then the level is brought down on day 3 to a maintanance level
warfarin is overlapped with LMW heparin until the INR is within the therapeutic range, above 2.0 for 2 consecutive days
What is the typical loading regime of warfarin?
10mg, 10mg, 5mg
What is a dangerous feature of warfarin?
patients have different levels of sensitivity to warfarin
Can warfarin be prescribed without checking for other drugs?
no, need to be aware of interactions between warfarin and other drugs that are metabolized by the same enzyme in the liver as warfarin is - p450
those drugs that inhibit p450 will potentiate the action of warfarin
conversely those drugs that induce p450 will inhibit the action of warfarin
What is the most important drug that interacts with warfarin and why?
alcohol
problem for alcoholics
will lead to high INR and high risk of bleeds
What are the side-effects of warfarin?
teratogenic – therefore LMW heparin is used in pregnancy instead
there is 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
How is warfarin reversed in a severe bleed?
Give vitamin K 2-10mg intravenously depending on INR level
will take 6-12 hours to work because of half life of factors being in excess of six hours
Patient can become refractory to re-loading with warfarin
How is warfarin reversed in a life-threatening bleed?
vitamin K and Octaplex containing the factors
25-50 units per kg octaplex
Fresh frozen plasma (FFP) can also be used
Why do we need to know how to reverse warfarin?
if patients come in with severe bleeds
How is fresh frozen plasma dosed?
according to the patients’ weight and their INR
How is heparin administered? Is it safe in pregnancy
always given by injection - parenterally
safe in pregnancy
What is the function of heparin and how does it work?
it potentiates the action of anti-thrombin
by irreversibly inactivating factors IIa (thrombin) and Xa
What are the two formulations of heparin and how are they administered?
Unfractionated heparin - IV or SC
LMW heparin - mostly s.c injections (can be IV but less common
sc = subcutaneous
What conditions will unfractionated heparin be used in?
not often used due to inconvenience
only used in patients with renal failure
Can unfractionated heparin be reversed?
it’s not very easy to reverse - can be partially reversed with protamine sulphate
How is unfractionated heparin monitored to make sure levels are safe?
looking at the APTT with target range of 1.5-2.5 x normal
have to monitor the platelet count
Why is the platelet count monitored in the use of unfractionated heparin?
level of platelets can fall due to development of thrombocytopenia
VTE is a rare complication resulting in heparin-induced thrombocytopenia or HIT
What is the dosage of unfractionated heparin?
Given i.v. with 5000U bolus and ~1000U/hour infusion
How (often) is LMW herparin administered to the patient and how is the dose calculated?
it is very convenient due to once daily subcutaenous injections
dosed according to patient’s weight
What are the main three LMW heparin formations?
Tinzaparin (Innohep) 175U/kg
Enoxaparin (Clexane) 1.5mg/kg
Dalteparin (Fragmin)
Does LMW heparin need to be monitored?
no, but usual renal function needs to be maintained - patient must have creatinine clearance of over 30ml/minute
How are NOACs administerd? How are they monitored? How safe are they?
it is orally available
no monitoring
good safety profile
What are the two classes of NOACs?
Dabigatran – direct thrombin (IIa) inhibitor
Rivaroxaban – direct factor Xa inhibitor
How effective are NOACs? What is a disadv?
trials show that they are just effective as warfarin and LMW heparin
disadv - the anti-coagulant action is irreversible
What is the dosing for dabigatran? How is it monitored and administered?
110mg bd or 150mg bd
confirm creatinine clearance > 30ml/min
administered orally
What is dabigatran and rivaroxaban used for?
used for treatment of DVTs and PEs
stroke prevention in atrial fibrillation
What is the dosing for rivaroxaban? How is it administered?
Dosing is 15mg bd for 3 weeks, then 20mg od
or 15mg od if CrCl is 15-50ml/min
How does aspirin work as an antiplatelet drug?
inhibits cyclooxygenase
is a very effective anti-platelet agent
it disables platelet function and activation and aggregation
What are the three main glycoprotein IIb/IIIa inhibitors?
Abciximab – monoclonal antibody
Eptifibatide – snake venom derivative
Tirofiban – blocks platelet aggregation
How do fibrinolytic agents work?
lyse fresh thrombi (arterial) by converting plasminogen to plasmin
What conditions are fibrinolytic agents used for?
acute MI recent thrombotic stroke major PE iliofemoral thrombosis strokes
Give examples of fibrinolytic agents
Tissue Plasminogen Activator (tPA, Alteplase)
Streptokinase
How are fibrinolytic agents administered? Describe the dosage
Administered systemically
Standardized dosage regimens aim to use within 6 hours
What are signs of shock?
hypotension, acute dyspnoea, collapse, syncope
What medication is used to treat a massive PE?
thrombolysis with tPA (Alteplase)
Tissue plasminogen activator (fibrinolytic)
iv unfractionated heparin
Monitor with APTR
