New anticoagulants: Moving on from scientific results to clinical implementation

Eerenberg, Elise S.; Es, Josien van; Sijpkens, Meertien K.; Büller, Harry R.; Kamphuisen, Pieter Willem

doi:10.3109/07853890.2011.606829

Cited by 8 publications

(7 citation statements)

References 50 publications

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“…Thrombin inhibitors and inhibitors of activated factor X such as dabigatran and rivaroxaban could be an attractive option [30]. These newer agents offer the advantage of oral administration, the absence of laboratory monitoring, and a mechanism of action which is independent of antithrombin [29].…”

Section: Anticoagulationmentioning

confidence: 99%

Portal vein thrombosis, cirrhosis, and liver transplantation

Francoz

Valla

Durand

2012

Journal of Hepatology

220

265

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Section: Anticoagulationmentioning

confidence: 99%

Portal vein thrombosis, cirrhosis, and liver transplantation

Francoz

Valla

Durand

2012

Journal of Hepatology

220

265

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“…Despite the need for effective and safe thromboprophylactic drugs in patients undergoing joint replacement therapy, few real-world data assessed the benefits of anticoagulants in this population. The translation of evidence-based guidelines into everyday clinical practice is not immediate [6]. Adoption of these recommendations in patients undergoing elective orthopedic surgery depends on combinations of patient-associated factors, including age, gender, and comorbidities, and physician-associated factors, including clinical practice and institutional compliance, as well as the widespread dissemination of guidelines and educational initiatives to reinforce published guidelines [7,8].…”

Section: Introductionmentioning

confidence: 99%

Venous thromboembolism after total joint arthroplasty: results from a Japanese multicenter cohort study

et al. 2014

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IntroductionReal-world evidence of the effectiveness of pharmacological thromboprophylaxis for venous thromboembolism (VTE) is limited. Our objective was to assess the effectiveness and safety of thromboprophylactic regimens in Japanese patients undergoing joint replacement in a real-world setting.MethodOverall, 1,294 patients (1,073 females and 221 males) who underwent total knee arthroplasty (TKA) and 868 patients (740 females and 128 males) who underwent total hip arthroplasty (THA) in 34 Japanese national hospital organization (NHO) hospitals were enrolled. The primary efficacy outcome was the incidence of deep vein thrombosis (DVT) detected by mandatory bilateral ultrasonography up to post-operative day (POD) 10 and pulmonary embolism (PE) up to POD28. The main safety outcomes were bleeding (major or minor) and death from any cause up to POD28.ResultsPatients undergoing TKA (n = 1,294) received fondaparinux (n = 360), enoxaparin (n = 223), unfractionated heparin (n = 72), anti-platelet agents (n = 45), or no medication (n = 594). Patients undergoing THA (n = 868) received fondaparinux (n = 261), enoxaparin (n = 148), unfractionated heparin (n = 32), anti-platelet agents (n = 44), or no medication (n = 383). The incidence rates of sonographically diagnosed DVTs up to POD10 were 24.3% in patients undergoing TKA and 12.6% in patients undergoing THA, and the incidence rates of major bleeding up to POD28 were 1.2% and 2.3%, respectively. Neither fatal bleeding nor fatal pulmonary embolism occurred. Significant risk factors for postoperative VTE identified by multivariate analysis included gender (female) in both TKA and THA groups and use of a foot pump in the TKA group. Only prophylaxis with fondaparinux reduced the occurrence of VTE significantly in both groups. Propensity score matching analysis (fondaparinux versus enoxaparin) showed that the incidence of DVT was lower (relative risk 0.70, 95% confidence interval (CI) 0.58 to 0.85, P = 0.002 in TKA and relative risk 0.73, 95% CI 0.53 to 0.99, P = 0.134 in THA) but that the incidence of major bleeding was higher in the fondaparinux than in the enoxaparin group (3.4% versus 0.5%, P = 0.062 in TKA and 4.9% versus 0%, P = 0.022 in THA).ConclusionsThese findings indicate that prophylaxis with fondaparinux, not enoxaparin, reduces the risk of DVT but increases bleeding tendency in patients undergoing TKA and THA.Trial registrationUniversity Hospital Medical Information Network Clinical Trials Registry: UMIN000001366. Registered 11 September 2008.

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“…There is a large body of evidence indicating that the thrombin-generating capacity of plasma is an important element in this systematic component and that it is the function that is diminished by antithrombotics. 6,7 The effect of antithrombotic treatment is, therefore, likely due to its effect on the thrombin-generating capacity of blood. This determines the therapeutic results of the treatment, which are measured as the rates of thrombosis and bleeding in the treated group in comparison to a reference group.…”

Section: Introductionmentioning

confidence: 99%

Large inter-individual variation of the pharmacodynamic effect of anticoagulant drugs on thrombin generation

2012

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Anticoagulation by a standard dosage of an inhibitor of thrombin generation presupposes predictable pharmacokinetics and pharmacodynamics of the anticoagulant. We determined the inter-individual variation of the effect on thrombin generation of a fixed concentration of direct and antithrombin-mediated inhibitors of thrombin and factor Xa. Thrombin generation was determined by calibrated automated thrombinography in platelet-poor plasma from 44 apparently healthy subjects which was spiked with fixed concentrations of otamixaban, melagatran, unfractionated heparin, dermatan sulfate and pentasaccharide. The variability of the inhibitory effect of the different anticoagulants within the population was determined using the coefficient of variation, i.e. the standard deviation expressed as a percentage of the mean. The inter-individual coefficients of variation of the endogenous thrombin potential and peak height before inhibition were 18% and 16%, respectively and became 20%-24% and 24%-43% after inhibition. The average inhibition of endogenous thrombin potential and peak height (ETP, peak) brought about by the anticoagulants was respectively: otamixaban (27%, 83%), melagatran (56%, 63%), unfractionated heparin (43%, 58%), dermatan sulfate (68%, 57%) and pentasaccharide (25%, 67%). This study demonstrates that the addition of a fixed concentration of any type of anticoagulant tested causes an inhibition that is highly variable from one individual to another. In this respect there is no difference between direct inhibitors of thrombin and factor Xa and heparin(-like) inhibitors acting on the same factors. Large inter-individual variation of the pharmacodynamic effect of anticoagulant drugs on thrombin generation

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New anticoagulants: Moving on from scientific results to clinical implementation

Cited by 8 publications

References 50 publications

Portal vein thrombosis, cirrhosis, and liver transplantation

Portal vein thrombosis, cirrhosis, and liver transplantation

Venous thromboembolism after total joint arthroplasty: results from a Japanese multicenter cohort study

Large inter-individual variation of the pharmacodynamic effect of anticoagulant drugs on thrombin generation

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