Guidelines for Warfarin Therapy

The following are guidelines for initiating and monitoring warfarin therapy.  Modifications for individual clinical circumstances may be necessary.  Please note that warfarin is the generic name for the most commonly used oral anticoagulant.  COUMADIN is the trade name for the most commonly available warfarin preparation.

Guidelines

Obtain a baseline PT (to be expressed as an international normalized ratio, INR), aPTT, and LFTs (ALT, AST, total and direct bilirubin, alkaline phosphatase) prior to initiating therapy.

The loading period is approximately 3-5 days for most patients before a stable maintenance phase is achieved.

Start warfarin on day 1 or 2 of heparin therapy.  Heparin should be continued for a minimum length of 5 days duration.  Exception: if treating an extensive DVT with or without pulmonary embolism, start warfarin on day 5 of heparin therapy.

If the patient is receiving TPN, remove the vitamin K from the amino acid solution before or as warfarin therapy begins.

If the patient is receiving formula, change the infant's diet as appropriate to a formula containing the least possible amount of vitamin K.  If the patient is exclusively breast fed, consider supplementation with a small amount of standard formula per day for a constant intake of vitamin K (required vitamin K is 1 microgram/kg/day, which is equivalent to about 120 cc of standard commercial formula daily).

If the patient is on hemodialysis, please see specific guidelines for nephrology patients.

If the patient is receiving other medications, for example antibiotics, which can affect warfarin, the loading dose must be adjusted.

Aim for an INR between 2.0 and 3.0 for the vast majority of patients.  Children with mechanical valves in place require an INR between 2.5 and 3.5.

When the INR is greater than 2.0 for 2 consecutive days, heparin can be discontinued.  Usually, the INR decreases slightly the next day.

If the baseline INR is 1.2 or greater (about 13 seconds or greater), reduce the loading dose to 0.1 mg/kg.

Warfarin Loading, Day #1

For all patients, the loading dose is 0.2 mg/kg po as a single dose.  If the patient has liver dysfunction, or has a Fontan, consider decreasing the loading doses to 0.1 mg/kg.

Warfarin Loading Days #2-#4

Subsequent loading doses are based on the INR respose as follows.  Please note that the dose reductions indicated below are critical to avoid overshooting the target range.
 
 
INR Warfarin Adjustment
1.1-1.3 Repeat initial loading dose
1.4-1.9 50% of initial loading dose
2.0-3.0 50% of initial loading dose
3.1-3.5 25% of initial loading dose
> 3.5 Hold until INR < 3.5, then
restart at 50% less than the
previous dose.

If the INR is not greater than 1.5 on day #4, contact the Hematology service.  The patient will be reassessed and a new loading dose be devised on an individual basis.

Long Term Maintenance Doses

These guidelines apply primarily to medically stable patients already established on long-term maintenance therapy.  Medically unstable patients or those completing the loading protocol may respond differently.  Close daily monitoring with individualized dose adjustment of such patients is essential until they are clearly established on maintenance therapy.
 
 
INR Warfarin Adjustment
1.1-1.4 Increase dose by 20%
1.5-1.9 Increase dose by 10%
2.0-3.0 No change
3.1-3.5 Decrease dose by 10%
> 3.5 Hold until INR < 3.5, then 
restart at 20% less than the
previous dose

Long Term Maintenance for Mechanical Valves

Use similar guideline as above, but maintain the INR between 2.5 and 3.5.

Outpatient Follow-Up

When the INR is greater than 2.0 for two consecutive measurements, the patient can be discharged.  The thromboembolism team will follow all outpatients in the region and ensure that the patients outside the region are monitored appropriately.

Monitor the INR within 3 days of discharge from the hospital.

Always draw an INR 5 to 7 days after initiating a new dose.  Use the maintenance guidelines for making these changes in dosage.

Once the patient has two INRs between 2.0 and 3.0 (or 2.5 and 3.5 for mechanical valves) taken 7 days apart, the interval for checking the INR can be stretched to 2 weeks; then if stable, to 3 weeks, and finally, if stable to 4 weeks.

The INR should be monitored a minimum of once a month.  Instruct the patient/parent to inform you of any changes/additions in medication or diet.

Duration of Treatment

The duration of therapy with warfarin will vary depending upon the underlying problem.  Children with mechanical heart valves or repeated thromboembolic complications will receive warfarin indefinitely.  Children with thrombotic event and a persistent, significant, underlying predisposing factor (e.g., continued presence of a central venous catheter; persistence of an antiphospholipid antibody, other) may be switched to low dose warfarin following 3 months of treatment with full dose warfarin, until the predisposing factor is no longer present.  Children with uncomplicated DVT will receive warfarin for 3 months only.

Warfarin Antidote

Vitamin K is the antidote for warfarin.  The dose to be administered and concurrent use of FFP or factor IX concentrate (containing factors II, VII, IX, X) are dependent on the clinical problem.  Consult hematology immediately if the patient is bleeding.  The following are guidelines only:

References

1.  Doyle, JJ, Koren, G., Cheng, MY, Blanchette, VS.  Anticoagulation with sodium warfarin in children: effect of a loading regimen.  J Pediatr 113:1095-97, 1988.
2.  Hirsh, J  Oral anticoagulant drugs.  Review article. N Engl J Med 324:1865, 1991.
3.  Hirsh, J, Levine, M.  Confusion over the therapeutic range for monitoring oral anticoagulant therapy in North America.  Review Article.  Thromb Haemostas 59(2):129-132, 1988.
4.  Hirsh, J, Polier, L, Deykin, D., Levine, M., Dalen, JE.  Optimal therapeutic range for oral anticoagulants.  Chest 95:5S-11S, 1989.
5.  Polier, L.  A simple nomogram for the derivation of international normalised ratios for the stadardisation of prothrombin times.  Thromb Haemostas 60(1):18-20, 1988.
6.  Braun, PJ, Szewczyk, KM.  Relationship between total prothrombin native prothrombin and the international normalized ratio (INR). Thromb Haemostas 68(2):160-164, 1992.
7.  Millenson, MM, Bauer, KA, Kistler, JP, Barzegar, S., Tulin, L, Rosenberg, RD.  Monitoring "mini-intensity" anticoagulation with warfarin: comparison of the prothrombin time using a sensitive thromboplastin with prothrombin fragment F1-2 levels.  Blood 79(8):2034-2038, 1992.
8.  Meade, TW, Roderick, PJ, Brennan, PJ, Wilkes, HC, Kelleher, CC.  Extracranial bleeding and other symptoms due to low dose aspirin and low intensity oral anticoagulation.  Thromb Haemostas 69(1):1-6, 1992.
9.  Andrew, M., Marzinotto, V., Brooker, LA, Adams, M., Ginsberg, J, Freedom, R, Williams, W. Oral anticoagulant therapy in pediatric patients: a prospective study.  Thromb Haemostas 71(3):265-269, 1994.
10.  Massicotte, P, Brooker, LA, Marzinotto, V, Andrew, M. Oral anticoagulation therapy in pediatric patients.  IN: Oral Anticoagulants.  Hirsh, J, Polier, L (eds).  Edward Arnold (Hodder & Stoughton), UK, Submitted 1994.

This protocol is adapted from Guidelines distributed by the Children's Thrombophilia Network, 1996.

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Last modification: April 15, 2001