The National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group meeting on June 14-15, 2012 in Bethesda, MD to explore the issues relevant to thrombosis (prevention, detection/surveillance, treatment) in pediatric cardiology and adult congenital heart disease patients. The goals of the Working Group were to:
The working group consisted of experts in pediatric cardiology, hematology, and neurology, adult cardiology and hematology, basic science of coagulation, imaging, and dissemination and implementation of guidelines along with representatives from the pharmaceutical industry and the Food and Drug Administration. The Working Group's charge was responsive to the NHLBI Strategic Plan Goals 1, 2, and 3.
Thrombosis, its sequelae, and complications related to management are increasingly recognized as important contributors to morbidity and mortality among children with congenital and acquired heart disease and adults with congenital heart disease. The prevalence and relevance of thrombosis in these populations are informed by unique factors, such as developmental and acquired abnormalities in thrombosis and fibrinolysis (e.g., physiologically low levels of anticoagulants, including antithrombin and protein C, in neonates and patients with functional single ventricle), and the presence of specific high-risk conditions (e.g., Kawasaki disease, perioperative state in patients undergoing open heart surgery, prosthetic heart valves). The pathophysiology, incidence, associated risk factors, clinical relevance, and optimal strategies for prevention, detection/surveillance, and management of thrombosis in these populations are poorly understood.
The insufficient evidence base in the field has been highlighted by recent clinical recommendations from the American College of Chest Physicians [Antithrombotic Therapy in Neonates and Children; Chest 2012;141;e737S-e801S] and the AHA Council on Cardiovascular Disease in the Young [Prevention and Treatment of Thrombosis in Children and Adults with Congenital Heart Disease and in Children with Acquired Heart Disease; under review]. These guidelines were characterized by absence of high-grade levels of evidence on which to base recommendations.
The introduction of newer anticoagulation therapies, such as anti-platelet agents and direct thrombin and Xa inhibitors, their success in adult patients, and industry's interest in developing pediatric trials combine to offer the opportunity to improve our current understanding of therapeutics, identify areas requiring further study, and develop a coordinated plan for testing these newer agents. Multidisciplinary and cross-agency coordination is critical when caring for a rare disease population; otherwise, isolated research efforts will pursue (ultimately unsuccessfully) a limited patient cohort.
The Working Group discussed the challenges and knowledge gaps in the area of thrombosis management in pediatric cardiology and adult congenital heart disease. To improve the knowledge base in this field, the Working Group made several recommendations.
The Working Group committee will develop a report of the meeting for publication in an appropriate professional journal.
Division of Cardiovascular Sciences
Division of Blood Diseases and Resources
Jonathan Kaltman, MD
Last Updated: September 2012