Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis
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Clin. Appl. Thromb. Hemost. · Jul 2009
ReviewState-of-the-art review: Assessing the safety profiles of new anticoagulants for major orthopedic surgery thromboprophylaxis.
The safety and efficacy of new anticoagulants are often initially tested for venous thromboembolism (VTE) prevention in patients undergoing major orthopedic surgery. Concern among surgeons about the risks for bleeding may result in suboptimal use of thrombophylaxis. ⋯ The definitions of bleeding events that clinical trials of thromboprophylaxis use in their assessment of new anticoagulants strongly influences each drug's perceived safety profile and may underestimate bleeding risks. Clinical studies of new anticoagulants urgently need standardization of bleeding definitions to allow intertrial comparability and to ensure consistent reporting of clinically relevant outcomes.
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Clin. Appl. Thromb. Hemost. · Jan 2007
ReviewIntravenous DDAVP and factor VIII-von Willebrand factor concentrate for the treatment and prophylaxis of bleedings in patients With von Willebrand disease type 1, 2 and 3.
The current standard set of von Willebrand factor (VWF) parameters used to differentiate type 1 from type 2 VWD include bleeding times (BTs), factor VIII coagulant activity (FVIII:C), VWF antigen (VWF:Ag), VWF ristocetine cofactor activity (VWF:RCo), VWF collagen binding activity (VWF:CB), ristocetine induced platelet aggregation (RIPA), and analysis of VWF multimers in low and high resolution agarose gels and the response to DDAVP. The BTs and RIPA are normal in asymptomatic carriers of a mutant VWF allele, in dominant type 1, and in recessive type 2N VWD, and this category has a normal response of VWF parameters to DDAVP. The response of FVIII:C is compromised in type 2N VWD. ⋯ FVIII/VWF concentrates should be characterised by labelling with FVIII:C, VWF:RCo, VWF:CB and VWF multimeric pattern to determine their safety and efficacy in prospective management studies. As the bleeding tendency is moderate in type 2 and severe in type 3 VWD and the FVIII:C levels are near normal in type 2 and very low in type 3 VWD patients. Proper recommendations of FVIII/VWF concentrates using VWF:RCo unit dosing for the prophylaxis and treatment of bleeding episodes are proposed and has to be stratified for the severity of bleeding, the type of surgery either minor or major and for type 2 and type 3 VWD as well.
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Clin. Appl. Thromb. Hemost. · Apr 2003
ReviewManagement of thrombotic and cardiovascular disorders in the new millenium.
Anticoagulants and antithrombotic drugs have played a key role in the prophylaxis, treatment and surgica/interventional management of thrombotic and cardiovascular disorders. There are several newer drugs which are currently developed for the anticoagulant management of cardiovascular diseases in both the medical and surgical indications. These include the low molecular weight heparins (LMWHs), antithrombin agents such as the Hirudin, Hirulog and Argatroban and indirect and direct anti-Xa drugs, represented by Pentasaccharide (Arixtra) and DX 9065a, respectively. ⋯ Since most of these newer anticoagulant and antithrombotic drugs are mono-therapeutic their therapeutic index is rather limited. Only in combination these agents can mimic heparins. At this time it is safe to state that heparin and its LMW derivatives will remain the anticoagulant of choice for cardiovascular indications until these newer agents have been validated in extended clinical trials in polytherapeutic settings.
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Thrombin is a central bioregulator of coagulation and is therefore a key target in the therapeutic prevention and treatment of thromboembolic disorders, including deep vein thrombosis and pulmonary embolism. The current mainstays of anticoagulation treatment are heparins, which are indirect thrombin inhibitors, and coumarins, such as warfarin, which modulate the synthesis of vitamin K-dependent proteins. Although efficacious and widely used, heparins and coumarins have limitations because their pharmacokinetics and anticoagulant effects are unpredictable, with the risk of bleeding and other complications resulting in the need for close monitoring with their use. ⋯ Such compounds inhibit thrombin by covalently binding to it, but this can result in toxicity and nonspecific binding. The development of reversible noncovalent DTIs, such as inogatran and melagatran, has resulted in safer, more specific and predictable anticoagulant treatment. Oral DTIs, such as ximelagatran, are set to provide a further breakthrough in the prophylaxis and treatment of thrombosis.
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Clin. Appl. Thromb. Hemost. · Jan 2000
ReviewExclusion and diagnosis of pulmonary embolism by a rapid ELISA D-dimer test and noninvasive imaging techniques within the context of a clinical model.
A negative rapid ELISA D-dimer test alone in out-patients with a low to moderate clinical probability (CP) on pulmonary embolism (PE) is predicted to safely exclude pulmonary embolism. The combination of a negative rapid ELISA D-dimer test and a low to moderate CP on PE followed by compression ultrasonography (CUS) for the detection of deep vein thrombosis (DVT) is safe and cost-effective as it reduces the need for noninvasive imaging techniques to about 50% to 60% of outpatients with suspected PE. A high probability ventilation-perfusion (VP) scan or a positive spiral CT consistent with PE and the detection of DVT by CUS are currently considered to be clear indications for anticoagulant treatment. ⋯ Serial CUS testing for the detection of DVT in patients with a low to moderate CP on PE and a nondiagnostic VP scan or negative spiral CT is predicted to be safe and will reduce the need for PA to less than 10% or even less than 5%. This noninvasive serial CUS strategy restricts the need for invasive PA to a minor group of patients (< 5%) with the combination of a low CP on PE and high probability VP scan or the combination of a nondiagnostic VP scan or negative spiral CT and a high CP on PE. Prospective evaluations are warranted to implement and to validate the advantages and the disadvantages of the various combinations of noninvasive strategies and to compare serial CUS testing versus PA in randomized clinical management studies of outpatients with suspected pulmonary embolism.