Warfarin Therapy

Daniel Raj
Contents
• Introduction
• Indication
• Contraindication
• Mechanism of Warfarin
• Initiation of Warfarin
• Monitoring of Warfarin therapy
• Warfarin Counselling
• Complications of Warfarin therapy
• Case study
• References
Introduction
• Prophylactic and therapeutic for venous and arterial thrombosis and
embolism.
• High risk/benefit profile of oral anticoagulants is a major impediment
to initiation of therapy.
• INR (International normalised ratio) measures the therapeutic
effectiveness of warfarin and its bleeding risk.
• The target range for most clinical indications is kept at 2.0 to 3.0.
• INR is affected by patient’s co-morbidities, diet and concurrent
medications.
Indication
• Deep Venous Thromboembolic (VTE) Disease
-Warfarin therapy should be continued for 6 weeks for patients with symptomatic
calf vein thrombosis.
• Atrial Fibrillation
-Prevention of thromboembolic stroke and events.
• Prosthetic Heart Valves
• Myocardial Infarction ; Lifelong anticoagulation therapy is indicated for:
(i) Post-MI patients in persistent AF.
(ii) Patients with LV thrombus should receive warfarin for at least 3 months.
• APLS
 Contraindication
1. Hemorrhage
• Warfarin is contraindicated for patients with active hemorrhage, cerebral
vascular hemorrhage (confirmed or suspected) and those with active
bleeding disorder
• Bleeding lesions of the gastrointestinal, respiratory and urinary tracts.

2. Pregnancy
• Crosses the placenta and fetal exposure to warfarin is associated
embryopathy, CNS abnormalities, fetal bleeding and increased foetal loss.
• Increases the risk of serious perinatal bleeding during delivery.
3. Miscellaneous Hypersensitivity to Warfarin
• Severe uncontrolled hypertension
• Severe vasculitis
• Recent (2-3 weeks) trauma (especially to the central nervous system)
• Neurosurgical procedures
• Aneurysms (cerebral or dissecting)
• Blood dyscrasias associated with haemorrhage or thrombocytopenia
Mechanism of Warfarin
Inhibits the enzyme vitamin K epoxide
reductase, which is required for the
carboxylation and activation of vitamin
K dependent coagulation factors
II(Prothrombin), VII, IX and X.
Initiation of Warfarin
-Pre-plan on the initiation of
individualised Warfarin
Therapy based on the
indication.
-Be sure to take the baseline
investigations to aid
monitoring during clinic
visits.
• Warfarin dosing should be calculated using weekly dosing.
• Increase or decrease up to 15% of weekly dosing, corresponds to
increase in INR of 1.0.
• The dosing of warfarin can be divided into two phases:
a. Initiation (with frequent INR testing)
b. Maintenance (with less frequent INR testing)
1. Initiation Phase
• A baseline INR should be obtained prior to initiating warfarin therapy.
• INR measurement within 7 days of initiation.
• Initiation dose may start with doses between 3 to 5 mg for the first three days and
subsequent dosing based on the INR response.
• Loading dose (≥10mg) during initiation of warfarin is not recommended.
• In elderly patients or in patients who are debilitated, malnourished, have CHF, have liver
disease, have had recent major surgery, or are taking medications known to increase the
sensitivity to warfarin (eg, amiodarone), the starting dose should be less than or equal to
3 mg/day.
• An initial effect on the INR usually occurs within the first 2–3 days. A therapeutic INR can
usually be achieved within 5 –10 days.
2. Maintenance Phase
• This only can be considered when INR achieved target ranged.
• Patients who had stable INR (INR in range > 6 months) can have
longer duration of INR monitoring (up to 12 weeks).
Food for thought
What is the meaning of increase or decrease by 15% corresponding
to an increase or decrease of INR by 1?

Scenario 1
Mr A is on T. Warfarin 3mg OD, during his visit to clinic his INR is noted
to be 1.5 , the target INR is 2-3, how much should I increase by weekly
and daily?

Current weekly dose= 21

15% of current weekly dose = 3
New weekly dose= Current weekly dose + 15% adjustment
New weekly dose= 21+ 3= 24
So the new dosage is T. Warfarin 3.5mg OD Mon to Sat and T. Warfarin 3mg OD
on Sun
Scenario 2
Mrs Y is on T. Warfarin 6mg OD,during her current visit to the
clinic her INR is 4 , the target INR is 2-3,how much should I
decrease the dose weekly and daily?

Current weekly dose= 42

15% of current weekly dose = 6
New weekly dose= Current weekly dose - 15% adjustment
New weekly dose= 42 – 6= 36
So the new dosage is T. Warfarin 5mg OD Mon to Fri and T. Warfarin
3mg OD on Sat and Sun
Warfarin Monitoring
Warfarin Counselling
1. Why?
-Leg clot (DVT)
-Lung clot (PE)
-Arrhythmia (Atrial fibrillation)
-Heart attack (MI)
-The placement of a mechanical or bioprosthetic heart valve.

By taking warfarin, it will treat your _________ (current event) and

prevent you from having another clotting event (thromboembolic event).
2. What?
-Warfarin is a blood thinner.
-Decreases formation of blood clots.
VTE (DVT, PE), AF: INR range 2-3
MVR or AVR with risk factors (AF, low EF, previous embolism,
hypercoagulable state): INR range 2.5-3.5.
-If you fall out of this range, your warfarin dose may change.
3. When?
-Must take your warfarin everyday and at the same time every day
(evening).
-If you miss a dose, take the dose as soon as you remember or before 12
midnight.
4. Which?
-Bleeding problems
-Bruising (careful with machinery, sharp object or aggressive sports)
- Bleeding gums (careful when brushing teeth – use soft toothbrush)
- Pink or brown urine
- Red or black stools
- Vomiting blood or material that looks like coffee grinds
- Pain, swelling, or discomfort
- Avoid NSAIDs (ibuprofen, naproxen) and aspirin for pain or inflammation
5. How?
-Large amounts of green leafy vegetables, which contain high amounts
of vitamin K, can lower the effects of warfarin (vitamin K works against
or antagonizes warfarin).
-Try to maintain a consistent diet, try to eat the same amount to leafy
vegetables every day.
- Avoid cranberry juice or products and alcohol.
Complications of Warfarin
• Haemorrhagic Stroke
• Traumatic or Non Traumatic ICB
• Traumatic or Non Traumatic hemopericardium
• Traumatic or Non Traumatic cardiac Tamponade
• Traumatic or Non Traumatic epistaxis
• Haemorrhagic pleural effusion
• UGIB
• LGIB
• Hemarthrosis
• PV bleeding
• Haematuria
Case Study 1
Mr A is a 55 yrs old gentleman with underlying AF, came to R8 with a
sudden onset of left sided facial asymmetry and left sided body
weakness. He is on T. Warfarin 5mg OD, the targeted INR for him is 2 to
3. How do we manage this patient?
OE: GCS 13, pupils inequal R-2mm,L- 3mm
BP 101/80
HR 80
RR 18
T 37
Spo2 99%
Lungs; Clear, Equal AE
CVS; DRNM
PA; Soft NT
CN – Isolated 7th Nerve palsy( Unable to smile and puff)
PN –Power on the BL UL/LL right side is 3/5
Δ TRO ICB secondary to overwarfarinisation
Airway
- Ensure adequate airway patency
Breathing
- Ensure SPO2 is maintained, oxygen supplement if indicated
Circulation
-Monitor BP every 15 minutes, Blood ix FBC- Normal, INR 9
Disability/Disposition
-IV Vitamin K 10 mg STAT
-Monitor GCS,KIV for intubation if GCS≤ 8
-Urgent transfer to tertiary centre for CTB and admission
Case Study 2
Mrs Y is a 68 yrs old lady with MVR is 2011. She is on T.Warfarin 3mg
OD. Noted during her clinic visit her INR is 1. She denied any bleeding
tendencies. How do we manage this patient? Any pertinent history?
Compliance?
-She is compliant to the medication.
-She takes green tea and consumes green leafy vegetable as she has
constipation for the past 2 months.
-She also complains of significant weight loss and have not been
tolerating as per usual.
OE: GCS full, pink, cachectic looking
BP/HR/SPO2/T are of normal limits
Lungs/CVS Unremarkable
PA mass at the left lumbar region, smooth surface, non tender, unable to get
below the mass
PR- Mass felt at the 6 and 9 o’ clock
Proctoscope- Mass seen at 6 and 9 o’ clock, no contact bleeding.
Other blood parameters are within normal range.
AXR- Prominent large bowel with apple core sign at the level of descending
colon.
 Δ
1. Tro GI malignancy
2. Underwarfarinisation secondary to poor dietary compliance

Disposition?
-Urgent SOPD referral for Colonoscopy
-Syr Lactulose 15ml ON for 1 week
-Advice on compliance to medication
-Advice on compliance to warfarin diet
-Continue T. Warfarin 3mg OD
-TCA in 1 week to review INR.
References
• Anticoagulant MTAC protocol 2nd Edition 2020
• Guideline C, Number R, Date I, et al. Protocol For Appropriate
Prescribing Of Direct Acting Oral Anticoagulants ( Doacs ) And
Management Of Haemorrhage And. NICE Guidel. 2019:1-18.
• CPG on Atrial Fibrillation 2012
• Guide to the Essentials in Emergency Medicine by Shirley Ooi and
Peter Manning 2nd Edition
Thank You!