Seminars in thrombosis and hemostasis
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Semin. Thromb. Hemost. · Feb 2008
ReviewCurrent and future prospects for anticoagulant therapy: inhibitors of factor Xa and factor IIa.
Indirect systemic and direct oral factor Xa and direct oral factor IIa inhibitors with improved pharmacologic profiles compared with heparins and vitamin K antagonists are currently in clinical development. This overview focuses on the indirect antithrombin dependent pentasaccharide derivatives of idraparinux and on the most advanced oral direct inhibitors to factor Xa (rivaroxaban and apixaban) and IIa (dabigatran). Specifically, the results of dose-finding studies for the prevention of venous thromboembolism after elective orthopedic surgery, the results of dose-finding studies for treatment of acute venous thromboembolism including prolonged prophylaxis of recurrent events, and the designs of ongoing clinical trials are reviewed.
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Semin. Thromb. Hemost. · Nov 2007
ReviewThrombolysis for pulmonary embolism and venous thrombosis: is it worthwhile?
Venous thromboembolism is a frequently occurring and potentially fatal disease characterized by short-term and long-term sequelae. Conventional treatment consists of heparin and vitamin K antagonists, but there is an ongoing controversy if more aggressive therapy, such as thrombolytic drugs, should be used in selected patients to achieve faster clot lysis in pursuit of better clinical outcome. A review of the literature shows that thrombolytic therapy is not recommended in the treatment of venous thrombosis. ⋯ In pulmonary embolism (PE), thrombolytic therapy is generally recommended for patients with massive PE and hemodynamic instability, despite scarce and inconclusive evidence. There is no evidence that thrombolysis has a benefit over standard anticoagulant treatment in normotensive patients with acute PE, but more research is needed to better identify the subgroup of patients with nonmassive PE in whom the risk-benefit ratio is most favorable. Until this group is defined and the benefit of thrombolytic therapy is demonstrated, thrombolytic therapy should only be considered in patients with signs of massive PE and hemodynamic shock.
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Semin. Thromb. Hemost. · Nov 2007
ReviewClinical relevance of the effects of plasma expanders on coagulation.
Patients with severe bleeding are often treated with colloids as plasma replacement fluids, including dextrans, gelatin-based solutions, or starches. Many of these agents will affect the hemostatic system beyond their effect on hemodilution. ⋯ In this overview, we discuss the effects of various plasma replacement solutions on the coagulation system and review the controlled clinical studies with different plasma expanders on clinically significant end points. We conclude that most plasma expanders have indeed marked effects at various points in the hemostatic system and that there are significant differences between various plasma replacement fluids but that clinically relevant effects on bleeding are mostly present if large volumes (i.e., > 1.5 L) are infused or if the patient has a concomitant or preexistent hemostatic impairment.
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Venous thromboembolism (VTE) in patients with cancer follows an aggressive course, and it is often resistant to traditional regimens of pharmacological prophylaxis and treatment. Anticoagulant-related bleeding is also common and can complicate VTE treatment as well as cancer therapy. Consequently, the most effective approach to reducing the burden of VTE and its associated morbidity and mortality is to provide appropriate prophylaxis. ⋯ Currently, low-molecular-weight heparins and oral vitamin K antagonists are the most commonly used anticoagulants for primary prevention in patients with cancer, but compliance with consensus guidelines is poor. Novel anticoagulants with a convenient and favorable risk/benefit profile may help to improve prophylaxis utilization and treatment. This review will provide a summary of the evidence on the primary prevention of VTE in patients with cancer.
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Thrombophilia is associated with a prohemostatic state and consequently with an increased tendency to develop thrombosis. In severe infection and sepsis, activation of coagulation frequently occurs, which contributes to the development of multiple organ dysfunction. Hypothetically, patients with thrombophilia may suffer from more severe coagulopathy in the presence of severe infection or sepsis, which may result in a more serious clinical course and an unfavorable outcome. This article reviews experimental and clinical evidence regarding such a relationship, with a particular focus on deficiencies of natural anticoagulant proteins (protein C and antithrombin), the factor V Leiden mutation, and genetic variation in the fibrinolytic system.