Seminars in thrombosis and hemostasis
-
Semin. Thromb. Hemost. · Jul 2007
Review Comparative StudyPreclinical and clinical characteristics of rivaroxaban: a novel, oral, direct factor Xa inhibitor.
There are several novel anticoagulants in development that target factor Xa(FXa)-the pivotal point of the coagulation cascade. One promising agent is rivaroxaban (a highly selective, oral, direct FXa inhibitor), which is in advanced clinical development for the prevention and treatment of thromboembolic disorders. Oral rivaroxaban may be given in fixed once-daily doses, with the potential for no coagulation monitoring. ⋯ Phase II studies of rivaroxaban for the prevention of venous thromboembolism (VTE) after major orthopedic surgery support these findings. The results also suggested that a total daily dose range of 5 to 20 mg rivaroxaban had similar efficacy and safety to enoxaparin, and that 10 mg rivaroxaban once daily was the optimal dose. This review assesses the preclinical and clinical characteristics of rivaroxaban, and discusses phase II findings with rivaroxaban for the prevention of VTE after major orthopedic surgery.
-
Semin. Thromb. Hemost. · Jul 2007
ReviewAntimetastatic activities of modified heparins: selectin inhibition by heparin attenuates metastasis.
Heparin, which is traditionally used as an anticoagulant but has a variety of additional biological activities, was shown in several retrospective and prospective clinical trials to have an effect on cancer survival. Experimental evidence from animal models consistently demonstrates that heparin is an efficient inhibitor of metastasis. To clarify the mechanism of heparin antimetastatic activity, several biological effects are being investigated. ⋯ Modified heparins characterized for heparanase inhibitory activity are also potential inhibitors of selectins. Selectin inhibition is a clear component of heparin inhibition of metastasis. The contribution of selectin or heparanase inhibition by heparin can provide evidence about its antimetastatic activity.
-
Semin. Thromb. Hemost. · Jun 2007
ReviewManagement of bleeding complications of hematologic malignancies.
Persons with hematologic malignancies bleed for a variety of reasons, including alterations in platelet function and numbers, clotting factor deficiencies, circulating anticoagulants, and defects in vascular integrity. The management of bleeding begins with a full characterization of the hemostatic defect. Vitamin K deficiency always should be considered and excluded by clinical history and laboratory tests. ⋯ Fresh frozen plasma is indicated infrequently; bleeding due to coagulopathies is better managed with cryoprecipitate if fibrinogen is low, or with clotting factor concentrates appropriate for the specific clotting factors found to be deficient. rFVIIa or activated prothrombin complex concentrate usually controls hemorrhage due to autoantibodies directed against factor VIII, and acquired von Willebrand's disease may be responsive to desmopressin or intravenous gamma globulin infusion. Antifibrinolytic agents often enhance other hemostatic therapies, but should be withheld if there is genitourinary bleeding or evidence of disseminated intravascular coagulation. Finally, plasmapheresis and immunoadsorption to remove paraproteins may be helpful when other measures fail to curb bleeding.
-
Semin. Thromb. Hemost. · Apr 2007
ReviewEmerging technologies in hemostasis diagnostics: a report from the Australasian Society of Thrombosis and Haemostasis Emerging Technologies Group.
Technology in hemostasis laboratories has evolved enormously during the last 30 years. Although many scientists and clinicians will remember the traditional tilt-tube techniques to screen for coagulation abnormalities and to monitor anticoagulant therapy, the hemostasis laboratory today uses a variety of modern technologies. ⋯ Although these advances in technology have resulted in greater capability, productivity, sensitivity, specificity, and ultimately, improvement in the clinical care of patients, controversies and limitations remain. This article highlights new and emerging technologies in hemostasis and discusses whether they have improved or are likely to improve laboratory diagnostics by specifically addressing the following: (1) Can new technologies help predict likelihood of thrombosis recurrence? (2) Has an understanding of the role of A Disintegrin-like And Metalloprotease with Thrombo Spondin type 1 motifs (ADAMTS13) in microangiopathy resulted in improved diagnostic methods for this disorder? (3) Does thrombelastography allow better definition of bleeding risk than conventional hemostasis assays, especially in settings of acute hemostatic pathology?
-
Patients with clinical conditions such as surgery, trauma, and acute medical illness have a transiently increased risk of venous thromboembolism and merit consideration for adequate thromboprophylaxis. The choice of an appropriate pharmacologic or physical means of prophylaxis should be made taking into account both the thrombotic and bleeding risk associated with patient-related factors and the type of surgery or other disease state involved. A large number of randomized clinical trials, meta-analyses, and guidelines developed by scientific societies worldwide have addressed this issue and have provided information and recommendations that should be considered carefully. ⋯ Patients at moderate thrombotic risk face a 10 to 20% risk of deep vein thrombosis (DVT) and require prophylaxis with low-dose unfractionated heparin or low molecular weight heparins (LMWHs) at a dosage < 3400 U once daily, or with graduated elastic stockings if their bleeding risk is high. Patients with an expected 20 to 40% DVT rate without prophylaxis are considered at high thrombotic risk and should be treated preferentially with LMWHs at high prophylactic dosage (> 3400 U). Patients undergoing major orthopedic surgery face a DVT rate > 40%, are considered at very high risk of venous thromboembolism, and should be given either LMWHs at high prophylactic dosage, fondaparinux, or vitamin K antagonists--either alone or in association with intermittent pneumatic compression devices.