S Schulman

..Unfortunately, there is a limited evidence base to inform decisions around management of these agents. We present our practice in these settings supported, where available, with literature evidence...

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..Dabigatran, which is administered in a fixed dose and does not require laboratory monitoring, may be suitable for extended treatment of venous thromboembolism...

..The VKAs have been subjected to many randomised trial addressing the initiation, intensity, monitoring and self-management. Extended anticoagulation and the selection for that is finally reviewed...

..This article reviews the data and, where applicable, compares them with other novel oral anticoagulants, particularly rivaroxaban, for which all phase III trials have been published...

..This review discusses the directions we could follow in such a tailored anticoagulation approach, referring to the limited evidence when available...

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..Laboratory testing for dabigatran will not be discussed in any detail in this article, which is instead the focus of other articles from this issue of Seminars in Thrombosis & Hemostasis...

..Guidelines recommend that patients receiving warfarin undergo international normalized ratio (INR) monitoring every 4 weeks...

..Evaluation of modulators of the phenotypic expression of hemophilia may benefit from a scoring system that reflects several aspects of the clinical severity instead of only one dimension...

..Knowledge of the clinical determinants of postoperative response could help avoid excessive anticoagulation in sensitive patients or avoid extended delays in achieving a therapeutic level in resistant patients...

..Additional options that may become available in the future are also discussed briefly...

..In addition, we review the possibilities to reduce the amount of factor concentrate by performing a combination of orthopaedic procedures and using local haemostatic agents or antifibrinolytic agents...

..The conclusions drawn should help clinicians make balanced decisions on the optimal duration of anticoagulation after an episode of VTE...

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..The intention is to also seek approval of this definition from the regulatory authorities...

..The agents are generally safe, with only a small increase of major bleeding, less with LMWH than with unfractionated heparin. The challenge is still to direct the efforts to the most appropriate patients...

..A bolus dose of 20 microg kg(-1) and thereafter maintenance of the FVII activity at approximately 3 IU mL(-1) appears effective and safe...

..The influence of the duration of anticoagulant therapy after venous thromboembolism (VTE) on the long-term morbidity and mortality is unclear...

..36, 1.93; P = 0.7). This complementary follow-up analysis confirms the benefit of oral ximelagatran 24 mg twice daily, administered without coagulation monitoring or dose adjustment, for the long-term secondary prevention of VTE...

..This mode of substitution was therefore safe, effective and well tolerated...

..We sought to identify easily available clinical characteristics that may influence the rate of normalization of prothrombin time when warfarin is stopped before surgery or invasive procedures...

..This review focuses on the novel therapies for VTE although the new anticoagulants will also play a major role in the management of arterial disease, which will be briefly presented...

..However, as the patient slowly stabilizes after appropriate interventions, it is necessary to de-escalate the treatment in accordance with decreasing net benefit of prolonged combination therapy...

..Well-controlled patients on warfarin may still have occasional International Normalized Ratios (INRs) outside the therapeutic range. It is unclear whether there is any benefit of a single-dose correction in this situation...

..The direct oral thrombin inhibitor dabigatran has a predictable anticoagulant effect and may be an alternative therapy to warfarin for patients who have acute venous thromboembolism...

..The intention is to seek approval of this definition from the regulatory authorities to enhance its incorporation into future clinical trial protocols...

..The aim of the present study was to assess total costs of warfarin-based anticoagulation in different health care models...

..Although new, orally available anticoagulants without need for monitoring or dose adjustments have been in clinical trials for a decade, none is approved yet, and will not be discussed in this review...

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..Whether the introduction of rivaroxaban is a change of paradigm will ultimately be decided in the eyes and mind of the beholder...

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..Patients with haemophilia appear to generate normal concentrations of APC during basal conditions. APC does not seem to be an important modulator of the phenotypic expression of haemophilia...

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..The length of time after an episode of venous thromboembolism during which the risk of newly diagnosed cancer is increased is not known, and whether vitamin K antagonists have an antineoplastic effect is controversial...

..For many patients with venous thromboembolism, secondary prevention with vitamin K antagonists is not extended beyond six months, since the risk of recurrence may be outweighed by the risk of major bleeding...

..Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use. Dabigatran is a new oral direct thrombin inhibitor...

..Oral ximelagatran appears to be a promising alternative to current anticoagulant therapy to limit the progression of acute DVT, and it seems to possess a wide therapeutic window...

..We aimed to test the efficacy and safety of oral rivaroxaban for the prevention of venous thromboembolism after total knee arthroplasty...

..Long-term use of oral ximelagatran, without coagulation monitoring or dose adjustment, should be feasible and well tolerated in a wide cross-section of patients for the secondary prevention of VTE...

..The aim of this study was to investigate prospectively whether low PAI-1 activity increases the risk for perioperative bleeding in patients undergoing transurethral resection of prostate, an organ with high fibrinolytic activity...

..This introduction attempts to explain the different mechanisms of action on a broad scale, and also includes a brief look at effects on inflammation and cancer...

..The optimal treatment regimen is individualized, taking into account a variety of risk factors, and re-evaluated regularly in case of prolonged therapy...

..Apixaban, a novel factor Xa inhibitor, may be an alternative treatment for such patients...

..0-2.5 in combination with low-dose aspirin, but is it really cost-effective? Finally, many controversies exist regarding anticoagulation during pregnancy...

..The purpose of this study was to investigate if patients with low PAI-1 activity have a lack of inflammatory response or a low insulin level...

..The only indications discussed here are hemophilia A or B with inhibitors or acquired hemophilia. Different recommendations may apply for other indications...

..The question of optimal monitoring needs further attention. Haemorrhagic complications were significantly less frequent when treatment was combined with the antifibrinolytic tranexamic acid...

..Thus, continuous infusion with this highly purified factor IX concentrate with improved viral safety is effective for surgery in haemophilia B...

..Low-dose oral vitamin K decreases the international normalized ratio (INR) in overanticoagulated patients who receive warfarin therapy. Its effects on bleeding events are uncertain...

..Prospective studies of the epidemiology and clinical significance of low plasminogen activator inhibitor type 1 (PAI-1) activity are lacking...

..In order to find the optimal balance of anticoagulation, avoiding recurrent events as well as major hemorrhage, it is important to know the impact of different risk factors over time...

..A number of recently discussed risk factors that are not routinely used in clinical practice might be useful for the identification of patients with a low risk of recurrence...

..Future studies should address the question of minimum steady-state levels required for haemostasis, comparisons with bolus injection using a randomized design and investigate the risk of inhibitor formation...

..The ideal solutions will perhaps only be achieved when we have learned how to combine the optimal duration with a time-adjusted decrease in oral anticoagulation...

..We sought to confirm our clinical impression and to gather data for the development of a guide to dosing these patients...

..In this paper we use new nomenclature for TAFI, and we believe that this recommended terminology for different forms of TAFI can simplify further standardization in TAFI investigation...

..Many studies on the influence of biochemical factors in the risk of recurrence have also been published recently. This review should be helpful in-the individual decision on how to tailor the duration of anticoagulation...

..In patients at a high risk for recurrence of VTE an initial period of regular intensity anticoagulation, followed by a low-intensity regimen, may provide effective and safe secondary prophylaxis...

..Although reports of the use of fondaparinux for this indication have thus far been favorable, the diagnosis of HIT in most cases was not based on definitive laboratory confirmation of heparin-dependent, platelet-activating antibodies...

..The experience is reviewed here and compared with data from the conventional bolus dose regimen...

..The relationship between the TAFI activation pathway and bleeding complications associated with hemophilia A, hemophilia B and VWD requires further investigation...

..For other genotypes, the decision regarding duration of therapy has to be based on the tolerance of the individual patient together with experiences from other studies...

..Thrombolytic therapy increases the risk of major bleeding 1.5-fold to threefold in patients with acute venous thromboembolism, ischemic stroke, or ST-elevation myocardial infarction...

..The evidence for established management strategies is reviewed and, finally, practical handling of the case is considered...

..The long-term risk for fatal pulmonary embolism (PE) after treatment of venous thromboembolism (VTE) may be an important factor in the decision to discontinue this treatment...

..Based on our low rate of observed major bleeding we conclude that 2.5 mg of oral vitamin K is a reasonable treatment for patients with INR values of more than 10 who are not actively bleeding...

..4% to 4.1%]; p-value for non-inferiority=0.002; p-value for superiority=0.34). In conclusion, similar maintenance control of the INR was achieved with a simple one-step dosing algorithm and a commercial computerised management system...

..The perioperative management of anticoagulation in patients who are having implantation of a pacemaker or implantable cardioverter defibrillator (ICD) is a common clinical problem in which best clinical practise is not established...

..The aim of this study was to investigate the clinical and biochemical effects of recombinant activated factor VII (rFVIIa) in the treatment of bleeding in children with liver disease...

..The special problems of keeping the balance between thrombosis and bleeding in this group of patients with need of anticoagulation due to mechanical heart valves or other thrombogenic factors are discussed...

..Conversely, the differentiated inhibition of the coagulation protease on vascular receptors may play a greater role for effects that are not traditionally considered as part of hemostasis...

..Low-molecular-weight heparin (LMWH) is often used; however, wound hematoma is a common complication...

..Cervical artery dissection is often treated with anticoagulants to prevent ischemic stroke. The risk-benefit ratio of anticoagulation versus antiplatelet therapy is unclear...

..The normalization of the bleeding time after valve surgery supports the hypothesis that the calcified cusps may interact with the platelet function...

..The minimal thrombin-complexing ability of the mutant AT-III protein that was observed was accelerated by heparin, but to subnormal levels...

..To report a case of inhibition of the effect of warfarin during treatment with ribavirin...

..Knowledge of these risk factors helps to weigh the risk and benefit in the selection of therapy in individual patients. Moreover, some risk factors can be modified or avoided if they are recognized...

..0 g/L) at diagnosis. MGUS patients with (vs without) thrombosis had no excess risk of MM or Waldenström macroglobulinemia. Our findings are of relevance for future studies and for improvement of thrombosis prophylaxis strategies...

..We performed a large retrospective cohort study to obtain more precise risk estimates...

..We conclude that screening and eradication therapy for infection with H. pylori in patients with congenital bleeding disorders is an effective and economic strategy...

..There was no clear evidence for a higher risk of recurrent VTE or bleeding across subgroups according to the potential prothrombotic factors analysed in this study...

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..We did a meta-analysis to assess from available evidence whether men and women have the same risk of recurrent venous thromboembolism after stopping anticoagulant treatment...

..In terms of treatment decision making for anticoagulant therapy, bleeding risk cannot be considered alone, ie, the potential decrease in thromboembolism must be balanced against the potential increased bleeding risk...

..At a mean unbound plasma concentration (Cu(ss)) of 335 micromol/L, NXY-059 was well tolerated, with no major safety concerns identified. In conclusion, NXY-059 does not appear to affect primary hemostasis...

..In conclusion, this study suggests that antithrombin alfa is a safe and effective alternative to human plasma-derived AT for treating hereditary AT deficiency patients at high risk for thromboembolic events...

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..Sequence comparisons indicate that X4 virus can be selected in vivo due to either absence of CCR5 receptors or relative increase of CXCR4 receptors...