Question

• A pediatric ICU patient develops edema and tenderness in her left leg, where a left venous femoral central line is in place. In pediatric patients with venous thromboembolic events (VTEs), is low molecular weight heparin (LMWH) better than unfractionated heparin and oral anticoagulation (UFH/OA) for treatment (i.e. prevention of recurrent thrombotic events and/or death)?

Clinical Bottom Lines

1. Currently, the treatment of VTEs in pediatric patients has been extrapolated from adult data which suggests LMWH as equally efficacious and safer than unfractionated heparin and coumadin.
2. To date, there has been only one randomized controlled trial in pediatric patients with VTEs comparing the use of LMWH versus unfractionated heparin with oral anticoagulation. The results supported that LMWH was just as efficacious and safe as UFH/OA, however the study was underpowered, and the data was not statistically significant.
   

Summary of Key Evidence

1. 96 pediatric ICU patients with diagnosed VTEs were randomized to receive either reviparin (LMWH) or UFH with coumadin for 3 months of treatment.
2. At 3 months, the reviparin group had 5.6% recurrence of VTE, versus 10% in the UFH/coumadin group.
3. At 6 months, the reviparin group had 5.6% recurrence of VTE, versus 12.5% in the UFH/coumadin group.
4. During the 3 months of treatment, the incidence of major bleeding events was 5.6% in the reviparin group, and 12.5% in the UFH/coumadin group. The incidence of minor bleeding was 88.9% in reviparin group, and 67.5% in UFH/coumadin. Of note, bruising at the site of injection of the LMWH was considered minor bleeding.
5. There were 5 deaths during the study period, one in the reviparin group and 4 in the UFH/coumadin group, none was attributed to VTEs. One of the deaths in the UFH/coumadin group was due to an intracranial bleed.
   

Additional Comments

• This study was underpowered due to slow recruitment, and none of the events demonstrated statistical significance when analyzed by the Fisher Exact Test.
• These results are not statistically significant, however, they do support the current practice in place of treating pediatric patients with LMWH for VTEs.

Citation

1. Massicotte P, et al. An Open-Label Randomized Controlled trial of low molecular weight heparin compared to heparin and coumadin for treatment of venous thromboembolic events in children: the REVIVE trial. Thrombosis Research 2003; 109:85-92.
2. Massicotte P, et al. An open-label randomized controlled trial of low molecular weight heparin for the prevention of centroal venous line-related thrombotic complications in children: the PROTEKT trial. Thrombosis Research 2003; 109:101-108
3. Monagle, et al. ACCP Consensus Conference on Antithrombotic Therapy. Chest 2001; 119.
   

CAT Author: Rachel Caskey, MD

CAT Appraisers: Jonathan Fliegel, MD

Date appraised: February 11, 2004