blood thinners Flashcards
Vit K antagonists - food interactions
- vitamin K found in health foods, food supplements, enteral feeds, large amounts of some green veg or green tea
- major changes in diet esp involving salads and veg and alcohol can affect AC control
- pomegranate juice increases INR
- heavy alcohol can decrease AC effect
what effect can illness have on warfarin
acute illness (including COVID-19 infection) may exaggerate the effect of warfarin and necessitate a dose reduction
warfarin dose
- initially 5-10mg on day 1, subsequent doses dependent on prothrombin time, reported as INR
- lower induction dose can be given over 3-4 weeks in pt who don’t require rapid AC
- lower induction dose in elderly
- maintenance 3mg - 9mg daily, take at same time each day
Name the 3 vitamin K antagonists
- warfarin
- acenocoumarol
- phenindione
how do vitamin k antagonists work
- antagonist effects of vitamin k
- take at least 48-72 hours for AC effect to fully develop
what to do if immediate effect is required with warfarin
- warfarin takes at least 48-72h for AC effect to develop fully
- immediate effect needed: give unfractionated or LMWH concomitantly
target INRs - 2.5 and 3.5
- 3.5 for recurrent DVT or PE in pt currently receiving AC and with an INR above 2
- 2.5 for everything else, including AF, treatment of DVT or PE, MI etc
An INR that is within …. units of the target value is generally satisfactory, larger deviations require….
0.5 units
dose adjustments
target INR for mechanical prosthetic heart valves depends on…
- depends on type and location of valve and pt-related RF
what to consider if embolic event occurs while anti coagulated at the target INR for mechanical prosthetic heart valves
- consider increasing INR target or adding anti platelet
do not use vitamin K antagonists 1st line in
- cerebral artery thrombosis or peripheral artery occlusion
what is more appropriate for reduction of risk in TIA
aspirin
what is usually preferred for prophylaxis of VTE in pt undergoing surgery
UFH or LMWH
main adverse effect of all oral ACs
haemorrhage
What to do if a pt is on warfarin and has major bleeding
- stop warfarin
- give phytomenadione by slow IV injection
- give dried prothrombin complex
- if dried prothrombin complex unavailable, fresh frozen plasma (but less effective)
- recombinant factor VIIa not recommended for emergency AC reversal
what to do if a pt is on warfarin and INR >8.0 with minor bleeding
- stop warfarin
- give phytomenadione by slow IV injection
- repeat dose if INR still too high after 24h
- restart warfarin when INR <5
what to do if pt on warfarin and has INR >8.0 and no bleeding
- stop warfarin
- give phytomenadione by mouth using IV prep orally (unlicensed use)
- repeat dose if INR still too high after 24h
- restart warfarin when INR <5
what to do if pt on warfarin has INR 5.0-8.0 and minor bleeding
- stop warfarin
- give phyomenadione by slow IV Injection
- restart warfarin when INR <5
what to do if pt on warfarin has INR 5.0-8.0 and no bleeding
withhold 1-2 doses and reduce subsequent maintenance dose
what to do if pt on warfarin has unexpected bleeding at therapeutic levels
always investigate possibility of underlying cause e.g. unsuspected renal or GIT pathology
when to usually stop warfarin before elective surgery
5 days before
what to do if INR on day before surgery is ≥1.5 (and warfarin has been stopped for 5 days)
give phytomenadione by mouth using IV prep orally (unlicensed use)
what to do with warfarin if haemostasis (bleeding stopped) is adequate following surgery
can resume warfarin at normal maintenance dose on evening or surgery or on next day
which pt may require interim therapy (bridging) with LMWH (using treatment dose)
- pt stopping warfarin before surgery who are considered to be at high risk of TE (eg. TE event within last 3 months, AF with previous stroke or TIA, mitral mechanical heart valve)
when to stop LMWH bridging therapy for warfarin before surgery and when to restart
- stop LMWH at least 24h before surgery
- if surgery high risk of bleeding, do not restart LMWH until at least 48h after surgery
how to reverse AC effect for pt on warfarin who require emergency surgery
- if emergency surgery can be delayed 6-12 hours, give IV phytomenadione to reverse AC effect
- if surgery can’t be delayed, give IV phytomenadione + dried prothrombin complex and check INR before surgery
Risk of bleeding with aspirin and warfarin DAT & clopidogrel and warfarin DAT - which one is lower?
lower bleeding risk with aspirin & warfarin
name the 4 DOACs
apixaban, dabigatran, edoxaban, rivaroxaban
Dabigatran is a reversible inhibitor of…
free thrombin, fibrin-bound thrombin and thrombin-induced platelet aggregation
apixaban, edoxaban and rivaroxaban are reversible inhibitors of…
activated factor Xa which prevents thrombin generation and thrombus development
omitted or delayed doses of DOACs
can lead to reduction in AC effect as effect diminishes 12-24h after lose dose taken
reversible agents are available for which DOACs?
dabigatran, apixaban, rivaroxaban
reversal agent for dabigatran
idarucizumab provides rapid reversal in life threatening or uncontrolled bleeding, or emergency surgery, or urgent procedures
reversal agent for apixaban, rivaroxabam
andexanet alfa for reversal in life threatening or uncontrolled bleeding
apixaban indications
- prophylaxis VTE (+ following knee, hip replacement surgery)
- prophylaxis recurrent DVT, PE
- treatment DVT, PE
- prophylaxis stroke and systemic embolism in non valvular AF and at least one RF (previous stroke or TIA, symptomatic HF, DM, hypertension, 75 and over)
indications: edoxaban
- prophylaxis stroke and systemic embolism in non valvular AF in pt with at least one RF (congestive HF, hypertensive, 75 and over, DM, previous stroke or TIA)
- treatment DVT, PE
- prophylaxis recurrent DVT, PE
indications rivaroxaban
- prophylaxis VTE (+ following knee, hip replacement surgery)
- treatment DVT, PE
- prophylaxis recurrent DVT, PE
- prophylaxis storke and systemic embolism in pt with non valvular AF and at least one RF: congestive HF, hypertensive, previous stroke or TIA, 75 or over, DM
- prophylaxis atherothrombotic events following an ACS with elevated cardiac biomarkers (in combination with aspirin alone, or aspirin + clopidogrel)
- prophylaxis atherothrombotic events in pt with CAD or symptoms PAD at high risk ischaemic events (in combination with aspirin)
indications dabigatran
- prophylaxis VTE following total knee replacement surgery (+ in pt taking concomitant amiodarone or verapamil)
- prophylaxis VTE following total hip replacement surgery (+ in pt taking concomitant amiodarone or veramapil)
- treatment and prophylaxis if DVT, PE (+ in pt with moderate RI, increased risk bleeding, + in pt taking concomitant veramapil)
- prophylaxis stroke and systemic embolism in non-valvular AF with one or more RF e.g. previous stroke or TIA, symptomatic HF, 75 or over, DM, hypertension, concomitant verapamil, moderate RI, in creased risk of bleeding
increased risk of bleeding with these drugs
- acenocoumarol, warfarin, phenindione
- alprostadil
- aspirin, ticagrelor, clopidogrel, prasugrel
- dipyrimadone, prasugrel
- NSAIDs: caution or avoid
- citalopram, duloxetine, escitalopram, fluoxetine, sertraline, paroxetine, vortioxetine, venlafaxine
- omega-3-acid ethyl esters - caution or avoid
- -tinibs
- alteplase, tecteplase
- apixaban, edoxaban, rivaroxaban
- bemiparin, dalteparin, enoxaparin, heparin, tinzaparin
- fondaparinux
- bismuth - caution
- nicotinic acid
- streptokinase, urokinase
the following drugs increase exposure to dabigatran, apixaban, rivaroxaban, edoxaban
- fluconazole, itraconazole, ketoconazole - avoid
- posaconazole - caution
- nirmatrelvir - avoid
- mirabegron
- ranolazine
- ritonavir - avoid
- tacrolimus - avoid
- ticagrelor - monitor and adjust dose
- verapamil, amiodarone - monitor and adjust dose
- clarithromycin - monitor
- dronedarone, avoid
- azithromycin, erythromycin
- Cs - avoid
the following drugs decrease exposure to dabigatran, edoxaban, rivaroxaban, apixaban
- fosphenytoin, phenytoin, carbamazepine - avoid
- rifampicin - avoid
- st johns wort
effect of alcohol on warfarin
heavy drinks: decreased AC effect
abx interactions: warfarin
basically they increase AC effect!!
- amox, ampicillin, benzathine benzylpenicillin, benzylpenicillin, fluclox, phenoxy, piperacillin, pivmecillinam : alters AC effect, monitor INR and adjust dose
- azithromycin, clarith, erythromycin: monitor, may increase bleeding
- ceftriaxone - increased bleeding
- chloramphenicol - increased AC effect
- ciproflox: increased AC effect, monitor INR
- demeclocycline, doxy, lymecycline, minocycline, oxytetrea, tetracycline: increased AC effect, monitor INR
- levofloxacin, moxifloxacin, ofloxacin: increases AC effect, monitor INR
- metro: increases AC effect, monitor INR and adjust dose
- trimethoprim: increase AC effect
anti-arrhythmic interactions warfarin
- amiodarone increases AC effect, monitor INR
- dronedarone might increase AC effect, monitor
- propafenone increases AC effect, monitor and adjust dose
warfarin and aprepitant
aprepitant decreases AC effect, monitor INR during treatment and for 14 days after
autoimmune drugs interactions warfarin
- azathioprine: decreases ac effect, monitor inr
- leflunomide increases ac effect, monitor inr
- mercaptopruine decreases ac effect, monitor inr
glucocorticoid interactions with warfarin
e.g. beclo, beta, hydrocortisone, dexamethasone
- these increase effects of warfarin, monitor inr
antiepileptic drugs and warfarin
e.g. carbamazepine, phenytoin, fosphenytoin
- decrease effects warfarin, monitor and adjust dose
fibrates and statins interaction with warfarin
- bezafibrate, ciprofibrate, fenofibrate, fluvastatin, rosuvastatin - increase AC effect, monitor INR and adjust dose