Deep vein thrombosis (DVT) and pulmonary embolism (PE), known collectively as venous thromboembolism (VTE), affect an approximate 900,000 people in the U.S. annually, resulting in several hundred thousand hospitalizations with an estimated mortality ranging from 100,000 - 300,000 deaths per year; the mortality from VTE is greater than deaths from motor vehicle accidents, breast cancer, and HIV combined. Patients who die from acute PE are most commonly not diagnosed, or even suspected until they are already dead. The major cause of death in acute PE is RV failure. VTE also carries a substantial public health burden, due to the current necessity for life-long clinical management. Despite therapy, a complication of VTE is chronic thromboembolic pulmonary hypertension (CTEPH), for which limited medical management options exist. There are clear clinical risk factors for acute PE, such as immobilization, trauma, surgery, malignancy, and others and obviously these are risk factors for CTEPH. However, the risk factors and pathogenetic events leading to the subsequent development of CTEPH after acute PE are much less clear.
The Division of Lung Diseases (DLD), National Heart, Lung, and Blood Institute convened a workshop in July 2011 to discuss the current state-of-the art in PE and CTEPH research. Multidisciplinary experts discussed the current concepts in VTE etiology and clinical management, identified gaps in our knowledge of CTEPH pathogenesis, and prioritized emerging opportunities to advance pulmonary coagulopathic disease research. Participants evaluated several risk factor conditions associated with VTE, including obesity, COPD, and trauma, in order to identify commonalities and specificities for coagulopathic disease development in co-morbid settings. Specific discussions of acute PE research opportunities included potential novel diagnostics for detecting disease, current and emerging anticoagulation approaches to clinical management of disease, appropriate use of inferior vena cava filters (IVCF), and early surgical intervention for severe acute PE resolution. The panel discussed research in CTEPH, covering basic science knowledge and gaps, translational research, and clinical practices and studies. Pathogenesis research using advanced technology and state-of-the-art techniques was heavily discussed. Topics included: 1) better understanding the interaction between blood cellular elements and the pulmonary vasculature (such as the role for mesenchymal progenitor cells and the fibrin microenvironment in disease development and progression, impact of reduced flow shear in pulmonary vascular remodeling, and effects of platelets and leukocytes in pulmonary vascular biology and pathobiology); and 2) integration of soluble factors and signaling in the pulmonary vasculature to produce vascular remodeling (such as thrombin-mediated endothelial barrier dysfunction, structural changes in fibrinogen against genetic backgrounds, and re-activation of developmental pathways such as Notch signaling in the lung vascular wall). Group discussion of the spectrum of topics from acute PE to CTEPH and the key issues and concerns that emerged led to specific research recommendations presented in this report.
Last Updated December 2011