Treatment Outcomes in Pediatric Patients with Pulmonary Embolism Using Low Dose Tissue Plasminogen Activator Therapy

Introduction:

Pulmonary Embolism (PE) is relatively rare in children but is associated with significant morbidity and many acute and chronic complications. Currently, based on ACCP guidelines, unfractionated heparin or low-molecular-weight heparin (LMWH) remains standard therapy for children with PE and systemic thrombolysis is reserved for life threatening thrombosis due to concerns with bleeding. Thrombolytic therapy has been shown to be more efficacious than anticoagulation alone in adults with PE but similar data in pediatric population is lacking. Specific guidelines for use of tissue plasminogen activator (TPA) in children with PE were created at Children's Hospital of New Orleans (CHNOLA) in 2008. We have used low dose systemic TPA (0.03 mg/kg/hr initially, increased to 0.05 mg/kg/hr if less than optimal response is seen within 24 hrs) together with unfractionated heparin (5 units/kg/hr) to achieve a goal PTT of 40-60 seconds. Thrombolytic therapy is continued until clot resolution is achieved, but not for a period longer than 72 hrs, at which point patients are transitioned to LMWH.

The aim of our study was to determine the effectiveness of systemic low dose TPA therapy in treatment of PE in the pediatric population and also to determine if there are increased bleeding complications.

Methods:

After IRB approval, a retrospective chart review of patient incidences (PI) with PE and treated with systemic TPA at CHNOLA between June 2008 and June 2014 was performed. Underlying risk factors for thrombophilia were noted. Responses were classified as complete resolution of thrombus (CR), improvement but no complete resolution (PR) or no change in thrombus (NR) based on imaging at the end of TPA treatment. Data were analyzed to determine the efficacy of low dose TPA in treatment of PE.

Results:

During the specified time, 16 PI were identified for which low dose systemic TPA therapy was used in children with PE. Median age was 13 years. Mean duration of TPA treatment was 51 hrs (range 17-72 hrs). All patients received simultaneous therapy with unfractionated heparin. Seven PI needed an increase in the dose of TPA infusion to 0.05 mg/kg/hr after 24 hrs due to partial or no response to therapy.

Nine (56%) PI had complete response, six (38%) were partial responders and one (6%) was classified as a non-responder. All PI were switched to LMWH at the end of systemic TPA. Duration of therapy with TPA did not affect response to treatment (p = 0.16) . There were no major bleeding problems. Furthermore, there were no complications that required TPA to be stopped. Table shows all the 16 PI, risk factors, duration/response to treatment and complications.

Conclusions:

To our knowledge, this is the first clinical study of low dose TPA use for PE in pediatric patients. Our results show that low dose TPA therapy is effective and relatively safe in treatment of PE in children. Further large-scale prospective trials are needed to validate the results of our study.