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Combined thrombolytic and anticoagulant therapy for venous thrombosis in children
M J Manco-Johnson1, R Nuss, T Hays
1Departments of Pediatrics, Surgery, and Radiology, University of Colorado Health Sciences Center and The Children's Hospital, Denver, CO, USA.
Insights
Combination therapy using urokinase and unfractionated heparin demonstrated safety and efficacy in pediatric deep vein thrombosis treatment. Further randomized trials are recommended to confirm these findings in children.
Area of Science:
- Pediatric Thrombosis
- Pharmacological Interventions
- Vascular Medicine
Background:
- Deep vein thrombosis (DVT) in children requires effective treatment strategies.
- Combination therapy offers a potential approach to manage pediatric DVT.
Purpose of the Study:
- To assess the safety and efficacy of combined urokinase and heparin therapy in pediatric patients with DVT.
- To evaluate clinical outcomes and resolution rates following this treatment regimen.
Main Methods:
- An open, nonrandomized clinical protocol was employed.
- Children received urokinase loading dose followed by unfractionated heparin, then warfarin.
- Outcomes were assessed at 48 hours and at 1-year follow-up using clinical and imaging methods.
Main Results:
- Thirty-two children were treated, with one thrombotic death and one pulmonary embolism.
- Half of the children achieved substantial clot lysis within 48 hours, with complete resolution and symptom absence at follow-up.
- Poor early responders experienced recurrent thromboembolic events; minor bleeding and systemic reactions were noted.
Conclusions:
- Combination therapy with urokinase and unfractionated heparin appears safe and effective for pediatric DVT.
- A prospective, randomized, controlled study is warranted to validate these results.
Objectives:
To evaluate safety, efficacy, and outcome after combination thrombolytic and anticoagulant therapy.
Study Design:
An open nonrandomized clinical protocol with prospective standardized monitoring and data collection. Children with a documented first episode of deep vein thrombosis were treated with urokinase 4400 U/kg load and per hour with unfractionated heparin at 10 U/kg/h. At 48 hours heparin infusions were increased to achieve a therapeutic level for 5 days. Children were given therapeutic warfarin for at least 3 months. Outcome was assessed at 48 hours and > or =1 year with history, physical examination, high-resolution imaging, and Doppler ultrasonography +/- impedance and photo plethysmography.
Results:
Thirty-two children were treated. There was 1 thrombotic death, 1 nonfatal thrombus progression, and 1 pulmonary embolism. At 48 hours half of the children showed substantial clot lysis, and on follow-up these children had complete resolution and had no symptoms. Three children with poor early clot lysis had recurrent thromboemboli, pulmonary embolism, or both, 2 had limb pain and swelling, and 2 had asymptomatic swelling. Two children had minor bleeding, whereas systemic reactions were common.
Conclusions:
Combination therapy in children (urokinase and unfractionated heparin) was safe and efficacious. A prospective, randomized, controlled study in children is needed.