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
cimetidine and warfarin
increases AC effect
cranberry, pomegranate, grapefruit - which one to avoid with warfarin
all potentially increase effect, esp pomegranate so avoid
disulfuram and warfarin
increases AC effect, monitor and adjust dose
enteral feeds and warfarin
vit K containing potentially decrease AC effect
anti-fungals and warfarin interactions
- fluconazole, ketoconazole, increases AC effect, monitor INR and adjust dose
- miconazole greatly increases AC effect of warfarin, avoid unless INR can be monitored closely and monitor for signs of bleeding
A pt on warfarin comes in wanting to buy a vitamin she had heard is good for joint pain. What do you do
avoid glucosamine, increases AC effect of warfarin!!
A patient on warfarin comes in to buy miconazole oral gel for some oral thrush. is this appropriate
no, avoid. greatly increases AC effect!!
paracetamol and warfarin - is this safe
increases AC effect of warfarin, monitor INR
tamoxifen and warfarin interaction
increases AC effect of warfarin, monitor INR
tramadol and warfarin
has been reported to increase AC effect of warfarin, caution
A patient on warfarin is to be started on a statin. Which ones do you recommend, which ones do you avoid and why
- Avoid fluvastatin and rosuvastatin - increased AC effect, requires monitoring
- Can use atorvastatin, simvastatin, pravastatin
how long after surgery would you start apixaban for prophylaxis of VTE following knee/hip replacement surgery
12-24h after surgery
Dose for apixaban: prophylaxis of VTE following knee replacement surgery & hip replacement surgery
- hip : 2.5mg BD 32-38 days, to be started 12-24h after surgery
- knee: 2.5mg BD for 10-14 days, to be started 12-24h after surgery
apixaban: treatment of DVT and PE dose, and maintenance
10mg BD for 7 days, maintenance 5mg BD
apixaban dose: prophylaxis of recurrent DVT or PE
2.5mg BD following completion of 6 months AC treatment
apixaban dose: prophylaxis of stroke and systemic embolism in non-valvular AF with at least 1 RF
- 5mg BD
- 2.5 BD in pt with at least 2 of the following: 80 or over, 60kg or less, serum creatinine 133mmol/L and over, crcl 15-29
Dabigatran dose for prophylaxis VTE following total knee replacement surgery
Adult 18–74 years:
- 110 mg for 1 dose, to be taken 1–4 hours after surgery, followed by 220 mg once daily for 10 days, to be taken on the first day after surgery.
Adult, 75 and over:
- 75 mg for 1 dose, to be taken 1–4 hours after surgery, followed by 150 mg once daily for 10 days, to be taken on the first day after surgery.
Dabigatran dose for prophylaxis VTE following total hip replacement
Adult 18–74 years
- 110 mg for 1 dose, to be taken 1–4 hours after surgery, followed by 220 mg once daily for 28–35 days, to be taken on the first day after surgery.
Adult 75 years and over
- 75 mg for 1 dose, to be taken 1–4 hours after surgery, followed by 150 mg once daily for 28–35 days, to be taken on the first day after surgery.
Dabigatran
treatment of DVT and PE
prophylaxis of recurrent DVT or PE
Adult 18–74 years
- 150 mg twice daily, to be given following at least 5 days treatment with a parenteral anticoagulant.
Adult 75–79 years
- 110–150 mg twice daily, to be given following at least 5 days treatment with a parenteral anticoagulant.
Adult 80 years and over
- 110 mg twice daily, to be given following at least 5 days treatment with a parenteral anticoagulant.
MHRA DOACs - increased risk recurrent thrombotic events in pt with antiphospholipid syndrome
- increased risk of recurrent thrombotic events associated with rivaroxaban compared to warfarin in pt with antiphosholipid syndrome and Hx thrombosis
- may be similar risk associated with other DOACs
- thus DOACs contraindicated in pt with antiphospholipid syndrome
- consider warfarin instead
reversal effects of andexanet alfa should be monitored using…
clinical parameters as anti-FXa assay results may not be reliable
what to do if pt are switched from warfarin to apixaban
stop warfarin before apixaban to reduce risk of over-AC and bleeding
DOACs and RI
- exposure to DOACs e.g. apixaban is increased in pt with RI so dose adjustments needed
- review pt regularly during treatment to ensure dose appropriate
Avoid apixaban if CrCl is
less than 15ml/min
Apixaban dose adjustment when used for prophylaxis of stroke and systemic embolism in non AF in pt with RI
2.5mg BD is serum creatinine 133mmol/l and over, 80 years and over, 60kg or less
or if CrCl 15-29
apixaban monitoring of pt parameters
- signs of bleeding or anaemia
- stop treatment if severe bleeding
apixaban pregnant and BF
avoid
Edoxaban doses
- body weight <61kg or CrCl 15-50 or taking Cs, dronedarone, ketocon, erythromycin: 30mg OD
- body weight 61kg and above: 60mg OD
Edoxaban max dose if concurrent Cs, dronedarone, erythromycin, ketoconazole
30mg
exposure of DOACs is increased in pt with
RI - dose adjustment
discontinue edoxaban …. hours before surgical procedure
at least 24h
edoxaban pregnancy and BF
- avoid
edoxaban RI dose adjustments
- avoid if CrCl <15
- if CrCl 15-50: 30mg OD
monitoring requirements edoxaban
- renal function before treatment and when clinically indicated during treatment
- hepatic function before treatment and repeat periodically if treatment duration >1 year
- signs of mucosal bleeding and anaemia in pt at increased risk
rivaroxaban dose: prophylaxis of VTE following knee and hip replacement surgery
knee: 10mg OD for 2 weeks, to be started 6-10h after surgery
hip: 10mg OD for 5 weeks, to be started 6-10h after surgery
rivaroxaban: dose for treatment of DVT/PE
- initially 15mg BD 21 days with food
- maintenance 20mg OD with food
rivaroxaban: dose for prophylaxis of recurrent DVT/PE
-10mg OD to be given following completion of at least 6 months of AC treatment
- consider 20mg OD with food in pt at high risk of recurrence
rivaroxaban: dose for prophylaxis of stroke and systemic embolism in pt with non valvular AF with at least one RF
20mg OD with food
rivaroxaban dose for prophylaxis of atherothrombotic events following ACS with elevated cardiac biomarkers in combo with aspirin alone or aspirin plus clopidogrel
2.5 BD usually 12 months
rivaroxaban dose for prophylaxis atherothrombotic events in pt with CAD or symptoms PAD at high risk of ischaemic events in combination with aspirin
2.5 mg BD
MHRA: rivaroxaban after trans catheter aortic valve replacement
- increase in all cause mortality, thromboembolic and bleeding events in clinical trial
- do not use rivaroxaban or any other DOAC for thromboprophylaxis in pt with prosthetic heart valves - use warfarin instead
which tablets of rivaroxaban need to be taken with food
advice for people who have difficulty swallowing
15mg and 20mg
(can be crushed and mixed with water or apple puree immediately before, and followed by food immediately after, ingestion in pt who have difficulty swallowing
can two ACs be prescribed to one patient
never (except when switching therapy, or when unfractionated heparin is given at doses necessary to maintain an open central venous or arterial catheter or for catheter ablation)
RI and rivaroxaban - cautions and when to avoid
caution if CrCl 15-29
avoid if CrCl <15
Rivaroxaban renal impairment: dose reduction when used for prophylaxis stroke and systemic embolism in pt with non valvular AF
- reduce dose to 15mg OD if CrCl 15-49
warfarin tablet colours
0.5mg: white
1mg: brown
3mg: blue
5mg: pink
warfarin cautionary and advisory label
warning: read the additional info given with this medicine
avoid cranberry
rivaroxaban cautionary and advisory labels:
for 15mg and 20mg tabs: take with or just after food, or a meal
for all: warning: read the additional info given with this medicine
contraindications for all vitamin K antagonists
avoid use within 48h pp
haemorrhagic stroke
significant bleeding
All vitamin K antagonists should be used with caution in bacterial endocarditis. if it is otherwise indicated, which one should be given
only warfarin
non-obvious cautions for all vit K antagonists
hyperthyroidism, hypothyroidism, uncontrolled hypertension, peptic ulcer
conception and contraception for all vit K antagonists
women of CB age should be warned of teratogenicity
use of vitamin K antagonists in pregnancy
- if possible avoid in pregnancy, esp in 1st and 3rd trimesters - difficult decisions may have to be made
- avoid in BF, risk of haemorrhage; increased by vitamin K deficiency
which vit K antagonist can colour urine
pheninidione - pink or orange
vit K antagonists - monitoring
- base line prothrombin determined, but do not delay initial dose whilst awaiting result
- INR determined daily or alternate days in early days of treatment, then at longer intervals (depending on response), then up to every 12 weeks
- more frequent testing if change in clinical condition, esp if associated with liver disease, intercurrent illness or drug administration
pheninidone labels
- this may colour your urine. this is harmless (orange pink)
- read the additional info given
cautionary labels for dabigatran
swallow whole, do not chew or crush
read addition info given with this medicine
once a bottle of dabigatran is opened, use within
4 months
patient has a prosthetic heart valve
which AC should you avoid
all DOACs
patient has antiphospholipid syndrome. what AC should you give
warfarin
DOACs CI
avoid dabigatran if RI …
less than 30
MOA dabigatran and how fast is onset of action
direct thrombin inhibitor with a rapid onset of action.
what electrolyte imbalance can heparins cause
hyperkalaemia
what to do if haemorrhage with heparin occurs
reversal agent is protamine sulfate, but it works better for UFH!
protamine sulfate, a reversal agent, is less effective for
LMWH
you need to choose a heparin for somebody who has high bleeding risk. which one?
UFH because it has a short half life so ideal in pt with high bleeding risk
which heparin has higher risk of heparin induced thrombocytopenia
UFH
which heparin preferred in RI
UFH
which heparin preferred in pregnancy
LMWH
use of warfarin in surgery - minor procedure, low risk of bleeding
performed within INR <2.5
restart warfarin within 24h procedure
use of warfarin in surgery, risk of severe bleeding
stop warfarin 3-5days before
give vit K if INR more than or equal to 1.5 on day of surgery
if pt high risk of TE, bridge with LMWH and then stop LMWH 24h before surgery and restart it 48h after
patient reports they have painful skin rash. which AC can cause this
MHRA warfarin reports of calciphylaxis
see GP if painful skin rash; if calciphylaxis is diagnosed, appropriate treatment should be started and consideration should be given to stopping treatment with warfarin.
most commonly observed in patients with known risk factors such as end-stage renal disease
Caution using this pain killer and warfarin together - MHRA
there is a risk of increased INR when warfarin and tramadol are taken together which can lead to potentially life-threatening bruising and bleeding;
dose adjustments for warfarin and/or additional INR monitoring should be considered when starting concomitant tramadol or other medicines.
65 yr old woman due to have mechanical heart valve replacement in 3 days. Consultant cardiologist is asking your advice regarding anticoagulation for this pt post surgery. Which one is appropriate?
rivaroxaban
dabigatran
warfarin
edoxaban
warfarin
DOACS are CI in prosthetic heart valves - increased risk of thrombosis
inducers and doacs
Rifampicin is predicted to decrease the exposure to Apixaban. Manufacturer advises use with caution or avoid.
this is with all DOACs and inducers - crapgps! severe interaction. avoid ideally
