Anticoagulant therapy: present and future.

Welcome to a very special issue of Seminars in Thrombosis & Hemostasis. This issue, on the topic of “Anticoagulant therapy: present and future,” is guest edited by Job Harenberg, a longtime member of the editorial board and supporter of the journal. Indeed, Dr. Harenberg most recently wrote a historical sketch for the journal around the many meetings that he organized on the anticoagulant and nonanticoagulant actions of glycosaminoglycans, a family of compounds that includes heparin.1 The journal’s founding Editor-in-Chief, Eberhard Mammen, was in attendance at several of these meetings. This period of time represents a special phase for Dr. Harenberg, who is approaching a stage of forced semiretirement, given his upcoming 65th birthday and an unfortunate compulsory retirement from university duties. Dr. Harenberg continues, nonetheless, to be an active contributor to the field of thrombosis and hemostasis, as attested by the current bumper issue that hehas assembled. Dr. Harenberg also clearly expresses his deep appreciation to the Dietmar Hopp foundation, which has provided substantial support for his research activities over many years as well as facilitating procurement of additional copies of the current issue for advancement of knowledge in the field. The initial contribution to this issue is by Agnelli et al,2 on the methodological quality of studies assessing thromboprophylaxis with low-molecular-weight heparin (LMWH), which represent the standard of care for prophylaxis of venous thromboembolism (VTE). The authors have reviewed the evidence supporting the use of the different LMWHs in VTE prophylaxis, in different clinical settings, and analyzed this progression over time. They conclude that the quality of studies supporting LMWH for VTE prophylaxis in different clinical settings is not homogeneous and inferior for studies performed before the year 1990. Also, clinical interchangeability of LMWHs in clinical practice remains a critical issue, and they propose that the selection of a product should be based on evidence available for each agent, and for each clinical indication derived from the clinical trials. The next article is provided by Prandoni et al,3 on the impact of residual vein thrombosis (RVT) on the long-term outcome of patients with deep venous thrombosis (DVT), treatedwith conventional anticoagulation, which is currently largely unknown. These authors have therefore assessed the incidence of recurrent VTE, postthrombotic syndrome (PTS), arterial thrombotic events, and cancer in patients with DVT, with and without RVT, and using a dataset of more than 800 consecutive patients with acute proximal DVT who had conventional anticoagulation. RVT was detected in almost half of the patients, and was more likely in males, in patients with previous VTE and in those with extensive thrombosis. During the 3-year follow-up recurrent VTE, PTS, arterial thrombosis, and cancer developed in twice the number of patients with, compared with without, RVT. They conclude that studies are needed to address the impact of the nonvitamin K antagonist (VKAs) oral anticoagulants (NOACs) on the development of RVT as well as the long-term complications of DVT. The third contribution, by Dahl et al,4 discusses arterial and venous thrombosis following trauma and major orthopedic surgery, as well as the molecular mechanisms and strategies for intervention. A variety of harmful effects can be triggered by trauma and major orthopedic surgery, with thrombin being one of the key players involved in such adverse processes, and DVT and pulmonary embolism (PE) being potential clinical outcomes. Protecting patients from VTE has been the main goal of preventive strategies, including thromboprophylaxis aiming in part to control thrombin generation and activation. However, recent years have seen expansion of knowledge related to cell destruction and release of substances that may cause organ damage, including small molecules such as RNAs and histones, which may cause additional cell destruction and organ damage at distal sites if released in huge amounts and disseminated systemically. Accordingly, there is an unmet need for therapies that prevent both vascular events and organ deterioration, and this article briefly reviews