Use of low molecular weight heparin in children with thromboembolic events; predictors for bleeding and recurrence on therapy

Abstract number: P0044

Revel-Vilk^* S., Sharathkumar† A., Chan‡ A. K. C., Marzinotto† V., Massicotte† P.

^*Hadassah Medical Center, Israel; ‡McMaster University, Canada †The Hospital for Sick Children, Canada;

Background  

Low molecular weight heparin (LMWH) is used frequently to treat thromboembolic events (TEs) in children. We previously reported the safety and efficacy of LMWH in 143 children with TEs. In this study, we determine predictors for bleeding, recurrence and progression of TE on therapy in an extended cohort of children treated with LMWH for a noncerebral TE.

Methods  

Comprehensive clinical data was obtained on a prospective cohort of children treated with LMWH for TEs from October 1994 to December 2001. All major and minor bleeding events and recurrence or progression of TE on therapy were recorded. Consecutive children treated with LMWH [Enoxaparin (Lovenox, Aventis Pharma Inc., Quebec, Canada)] for > 4 days for a noncerebral TE were included in this study.

Results  

A total of 232 children (142 boys, 90 girls) were treated with LMWH at a median age of 43 days (1 days to 17.3 years). The majority of these children were <2 months of age (neonates) (140/232, 60%); 94 were born at term (>37 gestational weeks) and 46 were born prematurely (<37 gestational weeks). The Enoxaparin dose given to keep an anti-Xa level of 0.5–1 IU mL^-1 was 1.7 mg ± 0.5 mg (mean ± SD) in neonates and 1 mg ± 0.3 mg in older children. Major and minor bleeding occurred in 16/232 (6.9%) and 23/232 (9.9%) of children, respectively. Bleeding was more frequent in premature neonates, 13/46, 28.3%, compared to term-neonates, 11/94, 11.7% and non-neonates, 15/92, 14.2% (P < 0.05). Recurrence and progression of TE on therapy occurred in 18/232 (7.8%) and 13/232 (5.6%) of children, respectively. Recurrence was more frequent in neonates, 15/140, 10.7%, compared to non-neonates, 3/92, 3.3% (P < 0.05). Recurrences in neonates occurred after a 24–48 h interruption of LMWH therapy for invasive procedures. Progression of TE on therapy was not associated with age. Underlying disease, vessel involved, location of the TE and the dose of LMWH were not associated with bleeding, recurrence or progression on therapy.

Conclusion  

Although LMWH is safe in most children, the frequency of bleeding events is higher in children compared to adults. Thus, LMWH treatment in children, especially premature neonates, should be used with caution to decrease bleeding events. In high risk neonates, recurrence of TE during short interruption of LMWH could perhaps be prevented by the use of unfractionated heparin with shorter half-life. Further investigation is needed to increase the safety and efficacy of LMWH in children.