Landmarks in Anti-Thrombin Drug Development: The Argatroban Story

This special and dedicated issue of Seminars in Thrombosis and Hemostasis includes the proceedings of the symposium “Landmarks in Anti-Thrombin Drug Development: The Argatroban Story.” It was held on July 11, 2007, as a satellite symposium of the 21st Congress of the International Society on Thrombosis and Haemostasis (ISTH), in Geneva, Switzerland.

The symposium was dedicated to the memory of the late Prof. Dr. med. Dr. h. c. Hans Klaus Breddin, who played an important role in the understanding of the pathogenesis of thrombosis, the development of new anti-thrombotic agents, and in particular the development of argatroban. The development of thrombin inhibitors as a new class of anticoagulants emerged with the work of close friends and colleagues of Klaus Breddin, Prof. Fritz Markwardt and Prof. Shosuke Okamoto, who had both worked on anti-thrombin drugs since the early 1950s. Thrombin is the key enzyme for producing a hypercoagulable state and pathological blood clot formation. Thrombosis in cardiovascular diseases and associated with heparin-induced thrombocytopenia (HIT), an adverse reaction to heparin, is mediated by thrombin. Argatroban and other direct thrombin inhibitors (DTIs) are approved in the United States, Canada, and several European communities for the treatment of thrombosis in patients with HIT. Klaus Breddin played a pivotal role in optimizing the clinical management of HIT and other thrombotic cardiovascular disorders with DTIs through his own scientific studies and by encouraging others.

Although HIT has such a devastating pathology, this disorder is often overlooked in a differential diagnosis. An effective way to reduce morbidity and mortality associated with HIT is to increase awareness among clinicians and health-care professionals. One aim of this symposium was to enhance the awareness of HIT among physicians at an international level. The ISTH Congress afforded a unique opportunity to reach clinicians and scientists from the European community, Japan, the United States, and other nations.

Patients with HIT are at an extremely high risk of thrombosis and experience vascular, cardiovascular, renal, neurological, and other types of thromboembolic events. Our ability to clinically manage patients with HIT, or at risk of developing HIT, has greatly improved with the development of new anticoagulant drugs. DTIs such as argatroban have created a valuable treatment option never before available to this patient population. A second aim of this symposium was to provide up-to-date information on the management of patients with HIT/HIT-associated thrombosis.

One of the current challenges that practicing physicians face is the management of patients with HIT who experience clinical complications. The third aim of this symposium was to provide information and new data on the use of DTIs in patients admitted to intensive care units, patients who require hemodialysis, coronary angioplasty, and stent implantation, and patients in other high-risk clinical situations.

Argatroban and related DTI drugs have revolutionized the management of thrombotic disorders associated with HIT. However, along with the advent of a new class of anticoagulants come new and diverse questions related to clinical applications, dosing, monitoring, safety, and efficacy. The mission of this educational symposium was to deliver new information to both practicing clinicians and research scientists who strive to make further improvements in these areas. This was accomplished with a distinguished panel of international faculty. The proceedings of their presentations and discussions are published here. Due to a timely need to provide an objective educational platform to address these issues, investigators with advanced knowledge in these areas who could provide up-to-date, state-of-the-art information were selected to author additional articles in this supplement.

Loyola University Chicago, Stritch School of Medicine, Department of Thoracic & Cardiovascular Surgery, and the Division of Continuing Medical Education sponsored this educational symposium. The organizers would like to extend a special thank you to the staff of the Division of Continuing Medical Education, Mamdouh Bakhos, M.D., chair of the Department of Thoracic & Cardiovascular Surgery, and John M. Lee, M.D., Ph.D., dean of the Stritch School of Medicine, for supporting this endeavor. We are particularly grateful to Prof. Henri Bounameaux, president of the 21st Congress of the ISTH, for his support and encouragement in the organization of this symposium. An unrestricted educational grant from Mitsubishi Pharma Corporation to support this meeting is gratefully acknowledged. We are also appreciative of the ISTH organization for including this satellite symposium in the 2007 Congress program.