i) General Information & Factors Affecting Warfarin Response
Warfarin Therapy & Factors Affecting Warfarin Response
Warfarin is the only oral anticoagulant readily available in NZ. There are currently two preparations
available (Coumadin and Marevan). These have different oral bio-availability, therefore, as far as possible,
patients should remain on the same product.
Contraindications (Warfarin)
Pregnancy
Warfarin is contraindicated in pregnancy. All pregnant women requiring treatment for thromboembolism
should receive subcutaneous LMWH treatment until delivery. After delivery warfarin can be used.
Breastfeeding
Warfarin is excreted in breast milk in very low amounts but is not considered to be a risk to the infant.
It is recommended that management of pregnant patients be discussed with a haematologist and obstetrician.
Risk Factors for bleeding complications of anticoagulation therapy
|
Risk factor category
|
Specific risk factors |
|
age |
>65 years |
|
cardiac |
Uncontrolled hypertension |
|
gastrointestinal |
History of gastrointestinal haemorrhage, active peptic ulcer, hepatic insufficiency |
|
Haematologic/oncologic |
Thrombocytopenia (platelet count <50 x109/l), platelet dysfunction, coagulation defect, underlying malignancy |
|
neurologic |
History of stroke, cognitive or psychological al impairment |
|
renal |
Renal insufficiency |
|
trauma |
Recent trauma, history of falls, (>3 per within previous treatment year, or recurrent, injurious falls) |
|
Alcohol |
Excessive alcohol intake |
|
Medications* |
Aspirin, COX-1-specific NSAIDS (COX-II inhibitors do not impair platelet function, but can influence warfarin effect), “natural remedies” that interfere with haemostasis. |
|
*Careful monitoring of warfarin effect is critical to minimise risk in patients taking multiple medications |
|
ii) Duration and Intensity of Anticoagulation
Intensity of Anticoagulation and Length of Treatment With Warfarin
|
Indication for Anticoagulation |
INR |
Duration of Anticoagulation |
Atrial Fibrillation |
2.0 – 3.0 |
Dependent on indication. See Atrial Fibrillation Guidelines
|
|
Cardioversion |
2.0 - 3.0 |
3 weeks before & 4 weeks after sinus rhythm maintained |
|
Prosthetic Heart Valves
Mitral mechanical valves implanted > 1990
Aortic mechanical valves implanted >1990 in aortic position |
2.5 – 3.5
2.5 – 3.0 |
Indefinite Consider addition of Aspirin 75 – 100 mg daily for: ¨ patients at high risk of systemic embolism ¨ Patients with double valves or high risk valves in mitral position ¨ patients who suffer systemic embolism on oral anticoagulants
|
|
Mechanical valves implanted <1990
|
3.0 - 4.0 |
Indefinite Consider addition of Aspirin 75 -100 mg daily for: ¨ patients at high risk of systemic embolism ¨ patients with double valves or high risk causes in mitral position ¨ patients who suffer systemic embolism on oral anticoagulants.
|
|
Treatment of DVT (start warfarin on day 1)
Recurrent DVT Whilst on Warfarin |
2.0 - 3.0
3.0 - 4.0 |
3 months ( Reversible risk factors)
6 months (Idiopathic risk factors )
Indefinite (if thrombophilia or re-thrombosis risk is greater than the risk of bleeding from warfarin therapy)
|
|
PE
Recurrent PE whilst on Warfarin |
2.0 - 3.0
3.0 - 4.0 |
6 – 12 months
Indefinite (if thrombophilia or re-thrombosis risk is greater than the risk of bleeding from warfarin therapy)
|
and who have more than one inherited or acquired thrombophilic states. Factor V Leiden (heterozygous) alone
is not an indication for lifelong secondary chemoprophylaxis. Any potential benefit of warfarin anticoagulation
must be balanced against the risk of major bleeding while on Warfarin which is > 1% per year.
2. In the rare case of Warfarin allergy, an alternative anticoagulant is adjusted dose sc unfractionated heparin (UFH)
- discuss this with the on-call haematologist. Continuing low molecular weight heparin (LMWH) therapy is a reasonable alternative,
but the dose required is not yet established with certainty. Alternatively, phenindione 10mg, 25mg and 50mg tablets are available
under Section 29. Pharmacy requires a minimum of four days notice to order this.
iii) Monitoring therapy with warfarin
The therapeutic level (or INR) of warfarin can change under many circumstances.
When to measure the INR daily for inpatients?
Patients newly commenced on warfarin
Patients previously on warfarin;
|
*An increase in monitoring the INR is required in the following situations : p Concomitant medicines which interact with warfarin Dose changes to these medicines Starting or stopping these medicines p Changes in diet Quantity of vitamin K rich foods p Decreased oral intake p Changes in alcohol consumption p Concurrent illness Acute diarrhoea Fever Malignancy Uncontrolled congestive heart failure Changes in thyroid function p Dose changes Intentional or unintentional warfarin dose changes Swapping patient to different brands of warfarin p Pharmacokinetic changes in warfarin: Hypoalbuminaemia (Albumin <30g/L) Liver failure Renal impairment (creatinine >0.2 mmol/L) |
iv) The Risk of Haemorrhage with Anticoagulants
Haemorrhagic Risk
Patients receiving anticoagulant therapy have an increased likelihood of haemorrhage (1).
HEPARIN:
· Treatment with unfractionated heparin (UFH) is associated with significant bleeding complications in 3% of patients (1).
· Trials of LMWH in the treatment of thromboembolism show that the incidence of significant haemorrhagic complications is around 1% ( 2,3 ).
WARFARIN:
· The likelihood of major bleeding (bleeding that is life threatening, involves a vital organ or requires hospital admission)
in patients receiving warfarin is 1 - 3% per year, and the risk of a fatal bleed 0.25% per year ( 4 ).
· Minor bleeding is seen in 7% of patients. Bleeding is most likely to occur within the first three months of anticoagulation.
· The INR is the most important determinant of haemorrhagic risk. In a 1996 study, the bleeding rate was doubled as the INR increased
from 2.0 – 2.9 to 3.0 – 4.4, quadrupled between 4.5 – 6.0 and was multiplied by five when the INR was above 7.0.
There is a consistent increase in major bleeding (including intracranial bleeding) when the INR exceeds 4.0 – 5.5.
· A 1997 trial found that each increase in INR by 0.5 multiplied the risk of major bleeding (mostly intracranial) by 1.43.
· In comparison to patients less than 70, those over 70 have a relative risk for bleeding of 1.75.
Assessment and Informed Consent
It is important to assess the bleeding risk of the patient prior to commencement of anticoagulation, and counsel the patient about the risks and benefits of warfarin therapy.