The use of vitamin k for reversal of over-warfarinization in children

Abstract

We have followed the discussion about reversal of warfarin therapy with interest (Pendry et al, 2001; Watson et al, 2001). An increasing number of young children are now receiving long-term warfarin, following surgery for major heart defects. Control of therapy is more difficult than in adults (Streif et al, 1999). Few data are available about warfarin reversal in children; fresh-frozen plasma is not appropriate for non-bleeding patients and may not produce adequate correction in bleeding patients (Makris et al, 1997). Blood products should be avoided in small children because of anxieties concerning possible transmission of infectious agents. Because low-dose vitamin K (0·5–1 mg) produces a lowering of a high International Normalized Ratio (INR) to near or within the therapeutic range in adults (Hung et al, 2000), we decided to extrapolate this to children with high INRs (venous INR > 8). The INR was successfully lowered in six out of seven cases (Fig 1) with a single dose of 30 µg/kg (1/10th of the full dose) given intravenously (doses ranging from 350 to 1000 µg). These six children were well and treated as outpatients. One other sick inpatient with deranged liver function tests required three doses to bring the INR into the therapeutic range. Our weight-adjusted regimen is safer than a universal dosage (0·5–2 mg subcutaneously). Even 0·5 mg (sufficient for many adults) is likely to be too high for most young children (too high for five of our seven children). Seriously ill children with liver dysfunction may require more than a single dose; this is one reason why it is important to confirm adequate correction at a chosen time interval: 4–6 h in those at highest risk or 24 h in milder cases. Low-dose i.v. vitamin K for warfarin reversal in children. Oral or subcutaneous vitamin K is effective in adults (Raj et al, 1999), but the INR fall is slower than i.v. injection. Our preferred route is therefore i.v., but in a child with poor venous access, the subcutaneous or oral route may be used, particularly if the INR is 6–10. A paediatric protocol should include specific advice that vitamin K should not be given intramuscularly to children on anticoagulants because of the risk of intramuscular haemorrhage. Paediatricians are more used to giving Vitamin K i.m., as this is standard practice for neonatal prophylaxis.