Neutrophil extracellular traps, scholarly debates, and public–private partnerships: highlights of the eighth annual Platelet Colloquium

Abstract

The first of the Colloquium’s three main sessions included discussion of the rising importance of neutrophil extracellular DNA traps (NETs), which represent an intersection of inflammation, infection, and thrombosis. NETs, a network of DNA fibers, histones, and nuclear proteins produced by nucleosome release from activated neutrophils, are a longrecognized component of the body’s innate immune response to infection. It has recently become apparent, however, that NETs form within blood vessels in response to injury and disease, providing a lattice for red cell adherence, platelet activation, and thrombus formation. Both DNAse and heparin have been shown to disrupt the NET structure, preventing thrombosis. This finding might have relevance in the development of novel therapeutic targets. In addition, the fact that polymers have been shown to bind to cell-free DNA in vitro might hold promise in the development of methods to assess thrombotic risk and status. Also in the first session, the Colloquium brought back a popular segment from 2012, a position debate between two leading researchers. This year’s topic was ‘‘Is There a Role for Antiplatelet Therapy in the Management of Atrial Fibrillation?’’ Arguing in favor was Steven R. Steinhubl, MD, of Geisinger Medical Center, Danville, Pennsylvania; arguing against was Elaine Hylek, MD, of Boston University Medical Center. Table 1 summarizes the main points from both sides of the debate. In the end, the debaters agreed that well-controlled studies will be needed to address many of the knowledge gaps relevant to this question. Session II contemplated the evidence regarding the use of antiplatelet therapies in several high-risk groups, with additional discussions about avenues for future investigation. Despite the available data, substantial knowledge gaps persist for the use of antiplatelet agents in persons with hemoglobinopathies, diabetes, other metabolic disturbances, previous stroke, and deep vein thrombosis. In addition, providers are uncertain about the optimal use of antiplatelet agents during transcatheter aortic valve implantation (TAVI), during ‘‘hybrid’’ coronary procedures, and as a bridge to noncardiac surgery. In Session III, the focus turned to regulatory sciences and governmental support of platelet-related research. Regulatory agencies recognize that the clinical trial ecosystem in the United States is under stress (Table 2). Representatives from the U.S. Food and Drug Administration (FDA) and the National Institutes of Health were on hand to outline the roles that government agencies can play in easing these stressors and facilitating the conduct of high-level research that both addresses public health needs and meets regulatory requirements for therapeutics in the U.S. Specific examples of the new approaches and philosophies embraced by the FDA include implementing new concepts to appropriately P. A. French (&) Chapel Hill, NC, USA e-mail: pat.french@leftlanecomm.com