The Indiana Center for Thrombosis Research (ICTR) exists to improve the lives of patients affected by blood clots by improving the diagnosis and treatment of venous thromboembolic disease through a multidisciplinary approach to scientific discovery, knowledge transfer and patient care. Our vision is that practitioners in Indiana will routinely use safe, rapid and low cost methods to diagnose and completely treat patients with blood clots, resulting in cost effective care and better quality of life. The ICTR will recruit and incorporate resources from academia, corporations and the community to create an internationally acclaimed, quaternary center for research and innovative treatment of persons with blood clots. Two multicenter, randomized controlled trials, published in January 2014 embody these ideas. In the first trial, we showed for the first time that a computerized method of probability assessment could reduce radiation exposure in emergency department patients with shortness of breath and chest pain. (Kline JA, Jones AE, Shapiro NI, Hernandez J, Hogg MM, Troyer J, Nelson RD. Multicenter, randomized trial of quantitative pretest probability to reduce unnecessary medical radiation exposure in emergency department patients with chest pain and dyspnea. Circ Cardiovasc Imaging. 2014 Jan 1;7(1):66-73). In the second trial, we found that a clot dissolving drug improved patient-oriented outcomes, including quality of life after severe pulmonary embolism. (Kline JA, Nordenholz KE, Courtney DM, Kabrhel C, Jones AE, Rondina MT, Diercks DB, Klinger JR, Hernandez J. Treatment of submassive pulmonary embolism with tenecteplase or placebo: Cardiopulmonary outcomes at three months (TOPCOAT): Multicenter double-blind, placebo-controlled randomized trial. J Thromb Haemost. 2014 Jan 31.) Both studies required collaboration and help from numerous medical specialties. The first trial has led to an ongoing a larger shared decision making trial, funded by PCORI and led by Mayo Clinic collaborator Erik Hess. We have put the TOPCOAT trial into practice in the Level I PE program being developed at Methodist and Eskanazi hospitals. In the Kline lab, one main focus is development of technology to directly deliver a recombinant variant plasmin protein on to intravascular blood clots. Because plasmin is immediately neutralized by circulating proteins, direct delivery to the clot surface causes clot lysis without increased bleeding risk.