Venous thrombosis affects approximately 1 in 200 hospitalized children. Important complications include shortness of breath and an inability to exercise in the first year after diagnosis resulting in a decreased quality of life. While considerable progress has been made in understanding the etiology and treatment of thrombosis in children, mechanisms contributing to complications after thrombosis in some patients or its absence in others remain largely unknown. In this proposal, we will evaluate potential mechanisms underlying shortness of breath and exercise intolerance after thrombosis. Our hypothesis is that a combination of heart, lung and muscle factors may explain these problems. We will enroll children between the ages of 8-20 years with thrombosis affecting either the lower legs or lungs, who will then undergo state-of-the art exercise and imaging assessments at 6 months after diagnosis.
Aim 1 will characterize the cardiac limitations and Aim 2 will assess the contribution of chronic thrombi in the lungs and deconditioning on pulmonary limitations after pulmonary embolism.
Aim 3 will investigate skeletal muscle problems after deep venous thrombosis and pulmonary embolism. We have developed and implemented a clinical program called the Pediatric Thrombosis and VTE Outcomes Program at the University of Texas Southwestern and Children's Medical Center, Dallas. This program risk stratifies all children initiating anticoagulation therapy and has prospectively captured important VTE complications in children after VTE for up to 2 years after diagnosis. Given this existing infrastructure and additional clinical sites from TX, we will be able to enroll adequate number of eligible patients to allow us to investigate potential mechanisms underlying functional limitations after thrombosis.
Venous thromboembolism (VTE) occurs in 1 in 200 hospitalized children. Up to 40% of children develop dyspnea and exercise intolerance after VTE, making VTE an important cause of disability in otherwise healthy children. The mechanisms of these functional limitations after VTE are unknown. The proposed research will investigate new mechanisms behind why children develop such VTE complications, and if successful, it will improve clinical outcomes and quality of life for children with VTE and inform the design of future clinical trials.
