Liquid Warfarin Formulation for Oral Anticoagulation of a Neonate with a Renal Vein Thrombosis


9 June 2012

Dear Editor,

Anticoagulation in a neonate is problematic. Warfarin is avoided due to the vitamin-K-dependent factors already being reduced, the influence of formula being supplemented with vitamin K and the fact that breast milk has minimal vitamin K.[1] Inconsistent feeding patterns may also complicate the issue.

A mother with a known risk factor of gestational diabetes[2] gave birth to a baby with left-sided renal vein thrombosis extending 12 mm cranially into the inferior vena cava. The child showed no evidence of thrombophilia.

Initially, the treatment was enoxaparin (low-molecular-weight heparin) administered every 12 h. It was recognised that the therapy would need to extend to 3 months due to the extent of the clot and that twice daily enoxaparin injections may be an unnecessary burden. Indeed, a liquid warfarin formulation was prepared (1 mg/mL) (Table 1), which allowed for easy oral administration using a graduated dropper.

Table 1. Preparation of liquid warfarin at 1 mg/mL
Warfarin sodium (Coumadin) 5 mg tablets pulverised in sufficient distilled water to produce a smooth magma80
Disodium hydrogen phosphate added and mixed well4 g dissolved in 50 mL distilled water
Tragacanth mucilage – mixed well80 mL
Sorbitol compound syrup – mixed well100 mL
Compound hydroxybenzoate solution (Australian Pharmaceutical Formulary)4 mL
Freshly distilled water to a final volume of400 mL

There were no apparent side effects using the liquid anticoagulant, and a reasonable degree of anticoagulation was achieved. The target international normalised ratio (INR) was determined at 2–3, monitored using a CoaguChek XS point-of-care machine (Roche Diagnostics GmbH, Mannheim, Germany). The child was given a loading dose of 1 mg, followed by 0.4 mg daily, with a final dose of 0.65 mg or as close as possible using the graduated dropper. The INR ranged from a minimum of 1.4 at initiation to 4.4, with an average INR of 1.9. The child had an average of 6.8 feeds per day, and during the 3 months, the child gained approximately 2.5 kg. The increasing weight did not appear to impact on the required amount of warfarin. Dosing was adjusted according to the INR levels obtained.

While variability was noted during the anticoagulation, it did not appear to be related to the number of feeds per day or to increasing weight. Although there was no discernible change in the daily feeding patterns, the quality of feeds cannot be determined and, perhaps, played a role in the INR variability. Preferably, the baby should stay with breastfeeds or bottle feeds and avoid a mixture due to the varying vitamin K intake.

The degree of anticoagulation achieved in this child was sufficient to stop any progression of the thrombus, and indeed, the thrombus regressed. While frequent monitoring was necessary to maintain a therapeutic INR, the number of interventions was far less than twice daily injections with enoxaparin. At 12 months of age, the child was well developed, with full renal function.