Low dose oral anticoagulation therapy in Chinese children with congenital heart disease

Abstract

Objectives: This study aims to evaluate the efficacy of a low dose warfarin regimen for Chinese children requiring anticoagulation therapy and its safety when monitored on an outpatient basis. Current recommendations are based on extrapolations from the adult experience and a high target international normalised ratio (INR) is adopted amongst the Western countries. Methodology: This is a 10-year retrospective study from January 1986 to June 1996. Effectiveness of warfarin therapy was monitored by the prothrombin time, standardised and expressed as the INR. A target INR of 1.5- 2.5 was adopted for children with cardiac diseases requiring anticoagulation therapy for primary and secondary prophylaxis against thromboembolism. From the clinical records, demographic data, induction warfarin dosage, changes of dosages and related events on follow-up, frequency of outpatient visits, complications and serial INR results were reviewed. Results: Thirty-five patients (23 boys, 12 girls) were included with a mean age at initiation of warfarin therapy of 8.4±5.8 years. Amongst these, 66% (n = 23) were after isolated valvar replacement, 28% (n = 10) after Fontan operation with or without valvar replacement and 6% (n = 2) after deep vein thrombosis. Regression estimate of the induction dose was 0.05-0.13 mg kg-1 in order to achieve the target INR range after 2 days of warfarin therapy. The daily maintenance warfarin dose was correlated with the bodyweight [dose (mg day- 1)=0.04 x bodyweight (kg)+ 0.87, r= 0.63, P<0.0001]. Young children required significantly higher daily warfarin maintenance dose when adjusted for bodyweight [dose (mg kg day-1)=antilog10{-0.02 x age (years)-0.80}, r=- 0.74, P<0.0001]. The mean maintenance warfarin dosage was significantly lower in patients after the Fontan operation, with or without valvar replacement, in the absence of apparent liver dysfunction. The total period of follow-up was 159 patient-years. No serious bleeding complications or embolic phenomena were documented. One patient died of thrombosis of the mitral valve prosthesis. The overall incidence of thrombosis was 0.6 per 100 patient- years. Conclusions: A low dose warfarin regimen to maintain a target INR of 1.5-2.5 provides adequate protection in Chinese children against thromboembolism whilst allowing safe outpatient monitoring of the anticoagulation status.