Thromb Haemostasis
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Bivalirudin is a direct thrombin inhibitor (DTI) frequently used for anticoagulation in the setting of invasive cardiology, particularly percutaneous coronary intervention (PCI). Bivalirudin has a unique pharmacologic profile: unlike other marketed DTIs, it undergoes predominant non-organ elimination (proteolysis), and has the shortest half-life (approximately 25 min). Its affinity for thrombin is intermediate between that of lepirudin (highest) and argatroban (lowest)--this helps explain why it interferes with functional clotting assays to an extent intermediate between that achieved by these two other DTIs. ⋯ Bivalirudin is also indicated for PCI with provisional use of glycoprotein IIb/IIIa antagonist therapy, and for patients with, or at risk of, heparin-induced thrombocytopenia (HIT), or HIT with thrombosis syndrome (HITTS), undergoing PCI. The bivalirudin development program has used a "quadruple" endpoint comprising a "triple" efficacy endpoint plus major bleeding - this approach anticipated the subsequent emphasis on strategies to improve clinical outcomes through bleeding reduction. Besides summarizing the key trials evaluating bivalirudin use for acute coronary syndrome (especially employing PCI), we review also the studies of bivalirudin as anticoagulant for "on-" and "off-pump" cardiac surgery, including both HIT and non-HIT situations.
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Several biological medicines derived from human and animal plasmas can effectively improve haemostasis in individuals with inherited or acquired defects in haemostasis. Factor VIII and factor VIII/vWF and factor IX concentrates are used to treat haemophilia A, von Willebrand disease and hemophilia B respectively. Cryoprecipitates are used to treat hypofibrinogenemia and von Willebrand disease where desmopressin (DDAVP) is ineffective or when plasma-derived factor VIII/vWF concentrates are unavailable. ⋯ This safety concern has lessened significantly in the past decade as a result of the institution of more effective pre- and post-donation screening that tests for potential pathogens, and institution of pathogen reduction strategies to which many plasma-derived biological medicines are now routinely subjected. This article considers the manufacture, standardization, clinical efficacy and adverse event profiles of the plasma-derived biological medicines currently used to promote haemostasis in patients with inherited or acquired functional defects in haemostasis. It also considers approaches employed to minimize infectivity of biological medicines derived from human and animal plasmas and to manage patients who develop antibodies (inhibitors) to clotting factor concentrate infusions.
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Dual antiplatelet therapy with aspirin and clopidogrel is currently the standard therapy after coronary stent implantation to prevent a life-threatening stent thrombosis. However, a variety of procedural and individual factors contribute to the individual patient risk and have to be taken into account to allow for an individual recommendation for both the duration and intensity of the antiplatelet therapy. Obviously, the benefit of the prevention of stent thrombosis by antithrombotic therapy has to outweigh the risk of severe bleeding complications. ⋯ However, in a subgroup of high-risk patients there is insufficient evidence for the benefit of conventional dual antiplatelet regimen. These include i) patients with an indication for anticoagulation, ii) patients with urgent need for an operation requiring a perioperative withholding of antiplatelet therapy, as well as iii) clopidogrel low responders. This review aims to provide a stratification to define patient collectives who may benefit from more individualized antithrombotic regimens on behalf of currently available literature and guidelines.
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The risk of stroke in atrial fibrillation (AF) needs to be assessed in each patient to determine the clinical and cost-effectiveness of thromboprophylaxis, with the aim of appropriate use of antithrombotic therapy. To achieve this, stroke risk factors in AF populations need to be identified and stroke risk stratification models have been devised on the basis of these risk factors. In this article, we firstly provide a systematic review of studies examining the attributable stroke risk of various clinical, demographic and echocardiographic patient characteristics in AF populations. ⋯ In patients at high risk of stroke, anticoagulation is cost effective, but not for those with a low risk of stroke. With the evidence available for stroke risk factors and the various alternative stroke risk stratification models, a review of these models in terms of the evidence on which they are devised and their performance in representative AF populations is important. The appropriate administration of thromboprophylaxis in AF patients would need to balance the risks and benefits of antithrombotic therapy with its cost-effectiveness.
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Review Meta Analysis
Thromboprophylaxis in cancer patients with central venous catheters. A systematic review and meta-analysis.
It was the aim of the review to determine the risks and benefits of primary thromboprophylaxis with anticoagulants in cancer patients with central venous devices. Medline, Central and Google Scholar databases were searched for randomized controlled trials (RCTs) in June 2006. Two reviewers extracted data and appraised the quality of RCTs. ⋯ The use of anticoagulants showed no statistically significant difference in the risk of overall bleeding (5 trials, 1,193 patients, RR 1.24, 95% CI 0.84-1.82, p = 0.28), and thrombocytopenia for heparin versus placebo (4 trials, 958 patients, RR 0.85, 95% CI 0.49, 1.46, p = 0.55) without any statistical heterogeneity (I(2) = 0%). In cancer patients with central venous devices, thromboprophylaxis has no significant effect on the risk of catheter related thrombosis or bleeding. The use of primary thromboprophylaxis in cancer patients with central venous catheters while not causing any harm provides no benefit.