In this section
Clinical Haematology: Warfarin Management Guideline
This guideline is intended to inform medical and nursing staff employed within the Clinical Haematology department. All anticoagulant management within RCH occurs under the supervision and guidance of a Consultant Haematologist. The guideline may be modified according to individual patient requirements.
Warfarin is the generic name for the most commonly used oral anticoagulant. There are 2 brands of warfarin, although they are distributed by the same company. Brands should not be used interchangeably. Both brands of warfarin colour-code their tablets. The following table describes the available tablet strengths and their corresponding colour. All new patients commencing warfarin should receive Coumadin.
Commencing Warfarin Therapy
Deep Vein Thrombosis/ P.E.
CVL clot prophylaxis
Ischaemic stroke / Moya Moya
Loading Dose - Day 1
Administer 0.2mg/kg orally as a single nocte dose, up to a maximum 5mg. (For patients with liver dysfunction, severe renal impairment, post-surgical or coagulopathic reduce this to 0.1mg/kg to a maximum of 5mg, or delay initiation). For adult patients commencing warfarin begin with a loading dose of 5mg.
Loading Dose - Day 2-4
Subsequent loading doses are based on individual INR response. The dose reductions in table below are critical to avoid "over-shooting" the target range.
Repeat initial loading dose
50% of initial loading dose
25% of initial loading dose
Hold until INR <3.5 then restart
At 50% less than previous dose.
If the INR is not > 1.5 on Day 4, the patient should be reassessed and the loading dose per kg increased based on the individual clinical need.
For patients commencing warfarin after cardiac surgery, the Cardiac surgeon is responsible for commencing warfarin and providing initial doses. Handover to the Clinical Haematology unit generally occurs on day 3-4, once wires and chest drains have been removed, however the Clinical Haematology team should be updated regularly regarding these patients. Handover on the day of, or day immediately prior to discharge may result in delay of discharge.
NB: warfarin is teratogenic in early pregnancy and reliable birth control is recommended. All patients of child bearing age should discuss contraception and pregnancy with a Haematologist before commencing warfarin. Warfarin is safe during breast-feeding.
Warfarin management is complex and affected by numerous factors. Management should be performed by someone experienced in warfarin dosing. Within the Clinical Haematology department, this includes all Haematology Consultants, the Clinical Nurse Consultants (Anticoagulation) and Haematology Registrars who have been trained and assessed as competent, as per the Clinical Haematology Registrar Manual.
INR monitoring tests are performed a number of different ways in the hospital and in the community.
Outpatient Warfarin Dosing
Prior warfarin dose
Recommended warfarin dose
Missed dose 3 days earlier
Started Bactrim for UTI yesterday$
Well, no changes. Last INR 3 weeks ago
7mg every other day
Mechanical valve. Restarted warfarin 2 days prior after procedure. LMWH 1mg/kg/day for 2 days
2mg (stable dose pre-procedure) for last 2 days
3mg, 2mg, 2mg
First INR above TTR in over 6 months with monthly INR monitoring. No changes in diet, medications or wellness
1mg, 2mg alternate nights
Diarrhoea and vomiting for 3 days; tolerating fluids now, but still not eating%
Withhold warfarin. Discuss with Consultant Haematologist.
Daily or second daily until recovered
$ Bactrim is known to increase warfarin sensitivity and push the INR higher. Reducing the warfarin dose in conjunction with a short interval until repeat INR measurement is recommended.
^ Patient will likely reach TTR within 5 days using the dose they have previously achieved their TTR with. As they have a prosthetic valve, LMWH cover is recommended until the INR is > 2.0
# The patient has been very stable. This one-off INR >3.0 may be an incidental finding. Reducing the dose of warfarin in response to 1 slightly elevated INR may create a chain of events where settling into the TTR again could be challenging. In the setting of a well child where no other causes of an elevated INR are evident, it is best to make no change but to re-test the INR within 1-2 weeks.
% Diarrhoea can cause the INR to increase quickly, due to the loss of Vitamin K generating normal flora in the gut. INRs great than 5 should be discussed with a Haematology Consultant. If obtained using point-of-care monitoring, the INR should be repeated using venous blood collection.
Every patient referred to Clinical Haematology for warfarin management requires comprehensive parent and/or patient education. This education must be specific to age, gender, underling health condition and developmental stage. Parent and patient education regarding warfarin therapy is a dynamic process that is never finalised. The Haematology Department aims to provide education to the entire family that recognised their past learnings, educational abilities and individualised needs. Families receive ongoing re-assessment of their level of understanding to ensure the delivery of learning opportunities that succeed in producing the desired knowledge outcomes.
Education should be commenced as soon as the patient commences warfarin therapy. If warfarin commences during an acute admission related to an underlying health problem, it is recommended to provide only minimal information during the admission, and continue a thorough education at an outpatients appointment within 2 weeks of discharge from hospital. After the initial (thorough) education session, we recommend the patient have a follow up outpatient appointment with the Anticogulation CNC and a Haematology Consultant in outpatients within 3-6 months. The purspose of this follow up appointment is to consolidate education and ensure the patient is in the system of ongoing outpatient follow up.
Parental/patient understand should also be assessed on a regular basis (at least annually) and knowledge deficits identified. Education targeting these knowledge deficits should be provided promptly.
Documentation stating what educational information has been provided and by whom should be clearly outlined in the patient’s medical record using the Warfarin Education template.
It must be assumed that all medications will influence a child’s response to warfarin, even if adults taking warfarin do not experience a change in INR in response to that medication. As a general rule, the impact of any medication change (including dose changes, commencing or ceasing a medication) should take 2-3 days before it impacts upon the INR. Patients and families are educated to discuss any medication changes with the Clinical Haematology team to facilitate identification of this risk factor for INR alteration. Medication changes should be documented in the warfarin database to facilitate future review should the child require that medication again (e.g. antibiotics). For families electing to commence over-the-counter medications (e.g. vitamins, herbal therapies etc) they should be informed of the risk that the medication may impact warfarin and the need to monitor an INR 3 days post commencing the medication.
Paracetamol based medications are safe to use with warfarin. Non-steroidal anti-inflammatory medications (e.g. Nurofen) should not be used as their anti-platelet activity introduces an additive risk of bleeding in the patient taking warfarin.
Unless expressly advised to do so by a medical doctor, patient taking warfarin should not take aspirin.
Patients requiring warfarin therapy are advised to have a healthy, varied diet. Consistency is recommended across the course of a week, but is not necessary day-to-day. For most families, a change in diet causing alteration to the INR is usually related to the child not eating due to intercurrent illness, school holidays (snacking eating practices versus portions eaten when at school) or overseas travel and associate changes in the kinds of food eaten. We do not recommend families portion control their child’s consumption of Vitamin K rich foods, such as broccoli, legumes or other leafy vegetables.
Patients requiring a fat-free diet (e.g. due to Chyle Effusion) whilst requiring warfarin will likely have changed warfarin requirements post-introduction of the diet. This reflects Vitamin K being a fat-soluble vitamin. Monitoring of the INR within 3 days of commencing a fat-free diet is recommended.
As previously stated, infant formulas and enteral feed solutions can impact response to warfarin as they are Vitamin K fortified. Any change to the volume of feeds administered or the interval of feeding (e.g. bolus versus continuous feeds) may impact warfarin response. It is recommended that an INR test be performed 3 days post such changes. In addition, ensure there is always at least 1 hours between the administration of any vitamin K containing formula and the administration of warfarin.
Changes in Health Status
Minor respiratory illnesses are unlikely to impact upon response to warfarin, provided the child continues to eat normally and does not require antibiotics. Any viral illness lasting more than 3 days should be reported to the Clinical Haematology team, to consider whether an alteration to the current management plan is required.
Gastroenteritis, and diarrhoea in particular, can cause a significant change in response to warfarin, causing the INR to increase rapidly. Diarrhoea can cause the INR to increase rapidly within 24 hours. Families are advised to call Haematology to inform them that their child has diarrhoea if symptoms persist for more than 24 hours. An INR should be performed within the next 24 hours and warfarin dose reduction is likely necessary.
Deterioration in a patient’s underlying illness may alter their response to warfarin. If families report such deterioration to Clinical haematology, it is wise to arrange for an INR to be performed in order to rule out a change in their management plan being necessary.
The major adverse event associated with warfarin is bleeding. The reported rate of major bleeding in patients requiring warfarin is less than 1% per patient year. In an audit of bleeding events at RCH, our major bleeding rate was found to be 0.05% per patient year. Families with a child commencing warfarin are educated regarding the use of routine first aid measures for any injury their child sustains. Should the bleeding experienced by a child on warfarin not be controlled using first aid measures, families are advised to go to Emergency for medical assessment. For patients taking warfarin primary thromboprophylaxis (having never had a blood clot), warfarin is usually withheld until the cause of bleeding is resolved. For patients at high risk of thrombosis in the setting of sub-therapeutic anticoagulation, Haematology Consultant review is required to prioritise the need for ongoing anticoagulation during an episode of bleeding.
Warfarin is a vitamin K antagonist. As osteocalcin is a vitamin K dependent protein, warfarin may also impact upon osteocalcin’s role in supporting bone growth and deposition. Patients are not advised to commence vitamin or mineral supplementation at the time of commencing warfarin. It is recommended patients have the recommended three serves of dairy foods per day and participate in weight-bearing exercise as tolerated. Patients requiring warfarin for more than 12 months should have a bone mineral density scan performed. If this scan result is within acceptable age-related parameters, repeat BMD testing should be performed every second year for as long as warfarin continues. Referral to Endocrinology may be necessary for patients with BMD results more than 2 standard deviations below age-related norms.
There are 3 options available to reduce a patient’s INR. This may be a desired action if the INR is well above the target therapeutic range or in the presence of bleeding and/or bruising. The appropriate option is dependent upon the urgency of INR reduction/normalisation or the patient’s risk of bleeding and/or bruising.
Withholding of warfarin doses
In the setting of an elevated INR in a child who is not unwell and has no bleeding or bruising, withholding warfarin will allow the INR to slowly drift into the target range. This option is desirable when maintenance of the child’s anticoagulation is desirable, and reversal of treatment is not clinically required.
Vitamin K reverses the effects of warfarin. The dose to be administered and the indications for concurrent FFP or prothrombin concentrate are clinically driven and should be directed by the Clinical Haematology consultant. In the presence of a high INR results without bleeding, vitamin K can be administered sublingually, subcutaneously or intravenously at a dose range of 0.5 to 2mg, depending on the child’s weight and INR value. NB. The half-life of Vitamin K is shorter than that of warfarin, so the INR may rise again after the administered Vitamin K wears off. Daily INR monitoring is recommended.
Fresh Frozen Plasma or Prothrombin complex concentrate
For patients with either an elevated INR or an INR within their target therapeutic range, but with concomitant bleeding, FFP or Prothrombin concentrate (Prothrombinex) can be administered to immediately reverse warfarin’s effect.
1. Monagle P, Chan A, Goldenberg N, Ichord R, Journeycake J, Nowak-Gottl U, Vesely S. Antithrombotic therapy in neonates and children: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-based clinical practice guidelines. Chest. 2012;141:e737-e801S.
3. Monagle P, Barnes C, Ignjatovic V, Furmedge J, Newall F, Chan A, DeRosa L, Hamilton S, Ragg P, Robinson S, Auldist A, Crock C, Rowlands S. Developmental haemostasis: Impact for clinical haemostasis laboratories. Thrombosis and Haemostasis. 2006;95:362-72.
4. Monagle P, Newall F. Anticoagulation in Children. Thrombosis Research. 2012;130:124-46.
5. Tran HA, Chunilal, SD, Harper PL, Tran H, Wood EM, Gallus AS. An update of consensus guidelines for warfarin reversal. Medical Journal of Australia. 2013; 198(4): 198-199
6. Recommendations for the development of a dedicated paediatric anticoagulation service. Newall F, Jones S, Bauman M, Bruce A, Massicotte P, Monagle P. Journal of Thrombosis and Haemostasis. 2014. (In press)
7. Quality Of Life Assessment in Children Requiring Oral Anticoagulant Therapy. Jones S. Monagle P, Manias E, Bruce A, Newall F. Thrombosis Research. 2013, 132 (1): 37-43.
8. Development of a Home INR Monitoring Program: Strategic Approach and Evaluation. Journal of Paediatrics and Child Health. Jones S, Newall F. Journal of Paediatrics and Child Health. 2013, 49(9): E357-E360
9. Recommendations for point-of-care home International Normalised Ratio testing in children on vitamin K antagonist therapy. Bauman M, Bruce A, Jones S, Newall F, Massicotte MP, Monagle P. Journal of Thrombosis and Haemostasis. 11:366-368. 2012.
10. Commencement of warfarin therapy in children following the Fontan procedure. Crone E, Hume E, George S, Saliba N, Newall F, Jones S. Thrombosis Research. 131(4): 304-307. 2013
11. HEADDSSS assessment for adolescents requiring anticoagulation therapy. Jones S, Alhucema P, Mertyn E, Monagle P, Newall F. Archives of Diseases in Childhood. 2012;97:5 430-433.
Prepared by the Clinical Haematology Department. August 2014