WARFARIN
Toxic dose
Toxic
Mechanism
Pharmacology
Half Life
Peak Level
Symptoms
Investigations
>2mg/kg  significant incr in INR within 72hrs
<0.5mg/kg unlikely risk, inc children
Inhibits Vit K metabolism  decr synthesis / activity of 2,7,9,10, protein C, protein S
Good PO, small VOD, 99% protein bound, enterohepatic circulation
Teratogenic in pregnancy (max at 6-9/40); not excreted in breast milk so safe in lactation
CI: age >75yrs, unlikely compliance, alcoholism, recent eye/SC OT, pericarditis, ICH, dementia
35 hrs
72 hrs (?2hrs)
Asymptomatic, or coagulopathy (bruising, petechia, purpura, gum bleeding, epistaxis, GI bleeding, haematuria);
exponential incr risk of bleeding with INR >5; 1% risk of bleeding within 48hrs if INR >8
In normal use: haem in 10%/yr (25% serious; 50% within therapeutic range; higher risk if INR >3; fatal in
0.25% mostly from ICH); macule  oedema  purpura  skin necrosis (if protein C/S def; can be prevented by
heparin for 1st 5/7 trt); atheromatous chol embolization
Incr INR ?cause: search for reason (eg. Change in dose, drug interaction – phenytoin, chloramphenicol,
cimetidine, erythromycin, TCA, omeprazole), sepsis, CCF, Vit K def)
INR takes 6hrs to start to change
If no therapeutic need: trt with Vit K and discharge; check INR in 48hrs as an OP
If therapeutic need: monitor INR Q6hrly
APTT incr in chronic trt
Treatment
Normal INR and no therapeutic need
If >0.5mg/kg ingested  give 10-20mg (10mg in children) PO Vit K
 discharge
 FU INR in 48hrs in adults, none in children
or 5-10mg IV Vit K
INR <5
Omit dose; if unintentional, consider 10% dose reduction
INR >5
If no therapeutic need
No bleeding: 10mg IV vit K  ?discharge, close FU
Active uncontrolled bleeding, clinically significant or major haem (ICH, spinal, intraab, intra-ocular,
spontaneous muscle haematoma, requiring invasive procedure to stop bleeding, SBP <90, oliguria,
>20 decr in Hb) and ?@ risk of significant bleeding or INR >9
 give
150-300ml / 1-2iu / 10-15ml/kg FFP (works fastest)
50iu/kg PTX (contains II, IX, X; small vol, only takes few mins to give, doesn’t need to be
thawed, blood grouping not needed; CI’ed in active thrombosis and DIC; SE = allergy, thrombosis)
5-10mg Vit K IV over 2-3mins (risk of anaphylaxis with IV vit K; rpt vit K BD if still incr INR;
onset of action 6-12hrs; XS vit K decreases effectiveness of FFP and PTX and makes re-initiation of
warfarin difficult)
Endpoint: INR <1.4
If therapeutic need: aim is to titrate Vit K; when trting, take into account risk categories below
No bleeding: 1-2.5mg PO Vit K if INR 5-9
5mg PO if INR >9
 recheck INR in 6-12hr  give repeat doses until INR <5
stop warfarin 1-2/7  restart at reduced dose once INR <5
start heparin if INR <2 if high risk
Life threatening bleeding: as above
High risk of bleeding (eg. Active peptic ulcer, recent OT in 2/52, on aspirin, plt <50) (? If INR >9):
consider CF replacement (INR 2-4 = 25iu/kg PTX, INR 4-6 = 35iu/kg, INR >6 = 50iu/kg)
Life threatening / high risk bleeding = haematemesis, melaena, intracranial bleed, ruptured AAA,
significant haemoptysis, aortic dissection, significant blood loss
Decontamination
Elimination
Antidote
Monitoring
Procedures
Charcoal if <1hr and patient usually on anticoagulants
No
Vit K
Onset: 6-12hr PO, 3-6hrs IV (?1-3hrs)
Admit those usually on warfarin; can often give Vit K then discharge those not on warfarin
Dental: wash mouth Q6hrly with 500mg tranexamic acid
Jt aspiration / pleural tap: target INR <2
Major OT: stop 3/7 before and give heparin once INR under therapeutic range
LOW RISK
MODERATE RISK
HIGH RISK
Atrial fibrillation without valvular heart
disease, previous stroke or embolism
Atrial fibrillation with valvular heart disease,
previous stroke or embolism
Mechanical mitral valve
Cardiomyopathy without heart failure,
previous stroke or embolism
Cardiomyopathy with heart failure, previous
stroke or embolism
Mechanical aortic valve with arrhythmia or
history of thromboembolism
Biological heart valves (except first 3
months)
Biological heart valves (during first 3 months)
Uncomplicated DVT (> 2 months)
Previous history of multiple PE/DVT
Cerebrovascular disease
Uncomplicated DVT (< 2 months)
Post AMI (mural thrombus prophylaxis)
DVT/PE with laboratory-confirmed
hypercoagulable state
Vascular surgical prosthetic grafts
Past systemic arterial emboli
Post vascular-stent insertion
Mechanical aortic valve without arrhythmia or
history of thromboembolism