Treatment Outcomes in Pediatric Patients with Pulmonary Embolism Using Low Dose Tissue Plasminogen Activator Therapy
Authors: Raulji Chittalsinh M , Silverburg Mary , Farge Justin , Velez Maria , Morales Jaime 
Published: October 2019

Abstract

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.
Table Age (Year) Risk Factor Duration of TPA (Hours) Response Complication 12 Y MTHFR heterozygous + high Homocystein level 72 PR Fecal occult blood positive 21 Y Hip surgery 1 month prior 24 CR No 19 Y Leukemia, Bone marrow transplant 3 weeks prior, central line 24 CR Left hand/forearm hematoma 6 days Prematurity, maternal cocaine use 72 NR No 16 Y Unknown 48 CR No 14 Y H/o Deep vein thrombosis 72 CR No 9 Y Leukemia, Downs syndrome 72 PR No 29 Y History of Fontan procedure 24 PR No 13 Y Downs Syndrome, hypothyroidism 48 CR No 11 Y Diabetes mellitus 72 PR No 11Y Right hip fracture 72 CR Oozing from IV sites 16 Y Oral contraceptive pills 48 CR Oozing from IV sites 17 Y Oral contraceptive pills 72 CR No 9 Y Diabetes mellitus, high lipoprotein a 72 PR Epistaxis 11 Y Right femur surgery 17 CR No 11 Y Diabetes mellitus, high lipoprotein a 72 PR Epistaxis
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.

Disclosures
No relevant conflicts of interest to declare.