Thromb Haemostasis
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The main purpose of anticoagulants is to diminish fibrin formation, thereby decreasing the risk of venous or arterial thrombosis. Vitamin K antagonist have been used for many decades in order to achieve reduced thrombotic risk, despite major drawbacks of this class of drugs such as cumbersome dossing and monitoring of anticoagulant status. To overcome these drawbacks of VKA, new classes of anticoagulants have been developed including oral anticoagulants for direct inhibition of either thrombin or factor Xa, which can be administrated in a fixed dose without monitoring. ⋯ Animal models revealed that VKA therapy induced both intima and media calcification and accelerated plaque vulnerability, whereas specific and direct inhibition of thrombin or factor Xa attenuated atherosclerosis. In this review we provide an overview of old and new oral anticoagulants, as well discuss potential pleiotropic effects with regard to calcification and atherosclerosis. Although translation from animal model to clinical patients seems difficult at first sight, effort should be made to fully understand the clinical implications of long-term oral anticoagulant therapy on vascular side effects.
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In addition to playing a central role in normal haemostasis, platelets make important contributions to host inflammatory and immune responses to injury or infection. Under pathophysiological conditions where platelet function is not tightly controlled, platelets also play critical roles in pathogenic processes underlying cardiovascular disease, uncontrolled inflammation, coagulopathy and in tumour metastasis. ⋯ Especially intriguing is the potential for platelet-driven coagulation to be modulated by NETs in plasma and interstitial spaces. These findings also reveal new perspectives related to improved therapy for venous thrombosis.
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During the past four years the phase III trials on stroke prophylaxis in atrial fibrillation and on treatment of venous thromboembolism have been completed for four new oral anticoagulants - dabigatran, apixaban, edoxaban and rivaroxaban. The studies have revealed advantages in terms of a reduced risk of bleeding, most importantly of intracranial bleeding. These anticoagulants also have favourable pharmacokinetics, eliminating the need for routine laboratory monitoring and dose adjustments. ⋯ These features are reviewed here. The management of patients in association with invasive procedures or major bleeding is also discussed. Finally, a strategy of how to select patients for warfarin or the new anticoagulants and thereafter possibly also among the latter is outlined.
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Review Meta Analysis
Benefit-to-harm ratio of thromboprophylaxis for patients undergoing major orthopaedic surgery. A systematic review.
Surgeons consider the benefit-to-harm ratio when making decisions regarding the use of anticoagulant venous thromboembolism (VTE) prophylaxis. We evaluated the benefit-to-harm ratio of the use of newer anticoagulants as thromboprophylaxis in patients undergoing major orthopaedic surgery using the likelihood of being helped or harmed (LHH), and assessed the effects of variation in the definition of major bleeding on the results. A systematic literature search was performed to identify phase II and phase III studies that compared regulatory authority-approved newer anticoagulants to the low-molecular-weight heparin enoxaparin in patients undergoing major orthopaedic surgery. ⋯ The exclusion of bleeding at surgical site which did not require reoperation shifted the benefit-to-harm ratio in favour of the newer agents. Variations in the definitions of major bleeding may change the benefit-to-harm ratio and subsequently affect its interpretation. Clinical trials should attempt to improve the consistency of major bleeding reporting.
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Newer oral anticoagulants offer several advantages over traditional agents (e.g. warfarin), but they are still associated with a bleeding risk and currently there is no validated reversal treatment for them. While there is little support for the use of fresh frozen plasma, and limited data available on the effects of activated recombinant factor VII, preclinical data suggest that prothrombin complex concentrates (PCCs) may have potential in this setting. PCCs are currently used to successfully reverse warfarin-induced anticoagulation; however, clinical evidence for their use with new oral anticoagulants is lacking, with most of the available data coming from preclinical animal studies. ⋯ Although there have been encouraging results, care must be taken in generalising findings from animal models and nonbleeding human subjects to the situation in bleeding patients. Ultimately, more evidence supporting anticoagulation reversal for new anticoagulants is needed, particularly regarding the treatment of bleeding in human patients in a clinical setting. According to the current evidence, use of PCCs may be considered a reasonable approach in dire clinical situations; however, a consensus has not yet been reached regarding PCC use or dosing, due to lack of clinical data.