fondaparinux has been researched along with edoxaban* in 16 studies
3 review(s) available for fondaparinux and edoxaban
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Efficacy of 11 anticoagulants for the prevention of venous thromboembolism after total hip or knee arthroplasty: A systematic review and network meta-analysis.
To systematically review the efficacy of 11 anticoagulants in the treatment of venous thromboembolism (VTE) after total hip or knee arthroplasty.. PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang Data, VIP, and China Biology Medicine databases were electronically searched for studies assessing the efficacy of different anticoagulants for the prevention of VTE after total hip or knee arthroplasty from January 1, 2010, to January 27, 2022. Two reviewers independently screened the literature, extracted data, and graded the evidence using Confidence in Network Meta-Analysis. The network meta-analysis was then performed using Stata 16.0 software and R 4.1.0 software.. A total of 61 articles were included. The results of network meta-analysis showed that apixaban, edoxaban, fondaparinux, rivaroxaban, and darexaban were the most effective anticoagulants for the prevention of deep vein thrombosis in patients undergoing total hip or knee arthroplasty (P < .05), while there was no difference in the efficacy among the anticoagulants for the prevention of pulmonary embolism (P > .05).. Apixaban, edoxaban, fondaparinux, rivaroxaban, and darexaban have the best efficacy for the prevention of VTE after total hip or knee arthroplasty. Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Fondaparinux; Humans; Network Meta-Analysis; Rivaroxaban; Venous Thromboembolism | 2023 |
Reversal of anticoagulants: an overview of current developments.
Several new anticoagulants have entered the clinical arena or are under clinical development. These drugs include indirect (fondaparinux) and direct oral factor Xa inhibitors (rivaroxaban, apixaban, edoxaban, betrixaban), and the direct thrombin inhibitor dabigatran. Especially the oral direct FXa and FIIa inhibitors overcome many of the shortcomings of heparins and vitamin K antagonists (VKAs). They are administered orally at a fixed dose; regular monitoring is not necessary; interaction with other drugs or nutrition occur less than with VKAs and they are at least as effective as VKAs for most indications tested. They are associated with about 50 % less intracranial bleeding than VKAs. Nevertheless, they are still associated with bleeding complications. Bleeding can occur spontaneously or as a result of trauma or urgent surgery. In such situations rapid reversal of the anticoagulant effect is highly desirable. For unfractionated heparin protamine, and for VKAs prothrombin complex concentrates are available as specific antidotes. Under clinical development are: for the direct and indirect FXa inhibitors a modified recombinant FXa (andexanet alpha), which lacks enzymatic activity; and for dabigatran a Fab fragment of a monoclonal antibody (idarucizumab). In addition a small molecule (aripazine) has entered phase I clinical trials, which seems to inhibit nearly all anticoagulants but VKAs and argatroban. This review summarises the current options and strategies in development to antagonise anticoagulants with a focus on the status of the development of antidotes for the oral direct FXa and FIIa inhibitors. Topics: Administration, Oral; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticoagulants; Antithrombins; Benzamides; Clinical Trials as Topic; Dabigatran; Factor Xa; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Hemostatics; Heparin; Humans; Infusions, Parenteral; Intracranial Hemorrhages; Polysaccharides; Protamines; Pyrazoles; Pyridines; Pyridones; Recombinant Proteins; Rivaroxaban; Thiazoles; Thrombosis; Vitamin K | 2015 |
Current management of venous thromboembolism in Japan: Current epidemiology and advances in anticoagulant therapy.
Venous thromboembolism (VTE), manifesting as either deep vein thrombosis or pulmonary embolism, is common worldwide including in Japan. The number of patients clinically diagnosed with VTE is increasing with the majority of cases occurring out-of-hospital and of milder severity. Cancer is the largest risk factor for VTE and VTE in cancer patients confers an increased 1-year mortality rate. However, the majority of VTE cases are considered "idiopathic" or "unprovoked." The limited efficacies of unfractionated heparin and warfarin have stimulated the development of new anticoagulant therapies. Recently, parenteral and oral administration of the Xa inhibitors fondaparinux and edoxaban, respectively, was approved in Japan. These agents have the potential to provide safer and more efficacious treatment options for VTE. Although further randomized studies are required to validate the utility of these agents, they are expected to substantially improve quality of life in VTE patients. This review summarizes the current status of VTE management in Japan focusing on current epidemiology and recent advances in anticoagulant therapy. Topics: Anticoagulants; Fondaparinux; Heparin; Humans; Japan; Polysaccharides; Pulmonary Embolism; Pyridines; Quality of Life; Risk Factors; Thiazoles; Venous Thromboembolism; Venous Thrombosis; Warfarin | 2015 |
1 trial(s) available for fondaparinux and edoxaban
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Effect of edoxaban on markers of coagulation in venous and shed blood compared with fondaparinux.
Edoxaban, an oral direct factor Xa (FXa) inhibitor, is in phase III clinical development for stroke prevention in atrial fibrillation and treatment of venous thromboembolism. The shed blood model allows for study of activated coagulation at a site of standardised tissue injury due to local release of tissue factor. The objective of this study was to evaluate the effect of three doses of edoxaban on markers of coagulation in shed and venous blood versus placebo and a standard prophylactic dose of fondaparinux. A total of 100 healthy male subjects were randomised to receive single doses of one of five treatments: subcutaneously administered fondaparinux 2.5 mg; orally administered edoxaban 30, 60, or 120 mg; or placebo. The primary objective was measurement of blood coagulation markers prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin (TAT) complex, and platelet activation marker β-thromboglobulin (β-TG), in venous and shed blood. Secondary objectives included pharmacokinetics, shed blood volume, and safety of edoxaban. Single doses of edoxaban caused rapid and significant decreases of F1+2, TAT, and β-TG in the shed blood model, indicating inhibition of thrombin generation and platelet activation. Inhibition was significantly less for fondaparinux versus edoxaban. Baseline-corrected F1+2, TAT, and β-TG values demonstrated sustained inhibition up to 24 hours for shed blood in the edoxaban groups but no significant inhibition in venous blood. Overall, edoxaban treatments were well tolerated. In conclusion, single oral doses of edoxaban 30, 60, or 120 mg caused rapid and sustained inhibition of coagulation up to 24 hours in the shed blood model. Topics: Antithrombin III; beta-Thromboglobulin; Biomarkers; Blood Coagulation; Clinical Protocols; Clinical Trials, Phase III as Topic; Drug Dosage Calculations; Factor Xa Inhibitors; Fondaparinux; Humans; Male; Peptide Fragments; Peptide Hydrolases; Platelet Activation; Polysaccharides; Prothrombin; Pyridines; Thiazoles | 2011 |
12 other study(ies) available for fondaparinux and edoxaban
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Edoxaban for the treatment of pulmonary embolism in hospitalized COVID-19 patients.
We aimed to investigate the clinical performance of edoxaban for the treatment of pulmonary embolism (PE) in hospitalized COVID-19 patients.. We conducted a retrospective analysis selecting hospitalized patients with COVID-19 admitted to our Institution from 20 May 2020 to 20 November 2020 with computer tomography (CT) detected PE at admission, treated with edoxaban after initial parenteral therapy. Clinical outcomes were compared between patients with and without ARDS at admission and between those with and without CT confirmed PE resolution.. 50 patients were included. Mean follow-up was 42.5 ± 10 days. No baseline differences were found between patients with ARDS (30%) and those without ARDS at admission. Patients with PE resolution (84%) were younger (. Edoxaban was an effective and safe treatment for acute PE in COVID-19 setting. Topics: Adult; Aged; COVID-19; Factor Xa Inhibitors; Female; Fondaparinux; Humans; Male; Middle Aged; Multivariate Analysis; Proportional Hazards Models; Pulmonary Embolism; Pyridines; Respiratory Distress Syndrome; Retrospective Studies; SARS-CoV-2; Thiazoles | 2021 |
Profile of Patients Diagnosed With Acute Venous Thromboembolism in Routine Clinical Practice: The RE-COVERY DVT/PE™ Study.
The safety and efficacy of nonvitamin K antagonist oral anticoagulants (NOACs) for the treatment of venous thromboembolism (VTE) have been established in randomized controlled trials, but limited data are available on their use in clinical practice across geographical regions.. In the international RE-COVERY DVT/PE observational study (enrollment January 2016 to May 2017), we sought to characterize the patient population and describe the prescribed anticoagulant. Patient characteristics and anticoagulants administered after objective diagnosis of VTE were recorded at the baseline visit and again at hospital discharge or at 14 days after the diagnosis, whichever was later.. A total of 6095 patients were included, 50.2% were male, and the mean age was 61.5 years. The most common comorbidities were hypertension (35%), diabetes mellitus (11%), cancer (11%), prior VTE(11%), and trauma/surgery (7%). Overall, 77% of patients received oral anticoagulants, with 54% on NOACs and 23% on vitamin K antagonists (VKAs); 20% received parenteral anticoagulation only. NOACs comprised about 60% of anticoagulant treatment in Europe and Asia but substantially less in Latin America (29%) and the Middle East (21%). For NOAC therapies, the distribution (as a percentage of the total cohort) was rivaroxaban 25.6%, dabigatran 15.5%, apixaban 11.3%, and edoxaban 1.7%. Treatment with NOACs was less frequent in patients who had cancer, chronic renal disease, heart failure, or stroke.. These findings enhance our understanding of baseline characteristics and the initial management of patients with VTE in routine practice. Topics: Administration, Oral; Adult; Age Distribution; Aged; Anticoagulants; Asia; Comorbidity; Cross-Sectional Studies; Dabigatran; Diabetes Mellitus; Europe; Factor Xa Inhibitors; Female; Fondaparinux; Heparin; Humans; Hypertension; Latin America; Male; Middle Aged; Middle East; Neoplasms; Postoperative Complications; Practice Patterns, Physicians'; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Venous Thromboembolism; Venous Thrombosis; Wounds and Injuries | 2020 |
[Antithrombotic Treatment of Pulmonary Embolism].
The present article addresses clinical challenges associated with the choice of the anticoagulant agent, the definition of the duration of anticoagulant treatment and the assessment of the risk-to-benefit ratio of prolonged anticoagulation for patients with pulmonary embolism (PE).Anticoagulation is performed with unfractionated heparin (UFH) in hemodynamically unstable patients and with low molecular weight heparins (LWMH) or fondaparinux in normotensive patients. In patients with high or intermediate clinical probability of pulmonary embolism, anticoagulation should be initiated without delay while awaiting the results of diagnostic tests. LMWH and fondaparinux are preferred over UFH in the initial anticoagulation of PE since they are associated with a lower risk of bleeding.All patients with PE require therapeutic anticoagulation for at least three months. The current 2019 guidelines of the European Society of Cardiology (ESC) recommend that all eligible patients should be treated with a non-vitamin K antagonist oral anticoagulant (NOAC) in preference to a vitamin K antagonist (VKA). In patients with active cancer, Apixaban, Edoxaban and Rivaroxaban are effective alternatives to treatment with LMWH.The decision on the duration of anticoagulation should consider both, the individual risk of PE recurrence and the individual risk of bleeding. The risk for recurrent PE after discontinuation of treatment is related to the features of the index PE event. While patients with a strong transient risk factor have a low risk of recurrence and anticoagulation can be discontinued after three months, patients with strong persistent risk factor (such as active cancer) have a high risk of recurrence and thus should receive anticoagulant treatment of indefinite duration. Given the favourable safety profile of NOACs (especially if a reduced dosage of Apixaban or Rivaroxaban is initiated after at least six months of therapeutic anticoagulation), extended oral anticoagulation of indefinite duration should be considered for all patients with intermediate risk of recurrence. Topics: Acute Disease; Dalteparin; Dose-Response Relationship, Drug; Drug Administration Schedule; Fibrinolytic Agents; Fondaparinux; Guideline Adherence; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Long-Term Care; Neoplasms; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Recurrence; Risk Assessment; Risk Factors; Rivaroxaban; Thiazoles | 2020 |
The clinical impact of edoxaban for the patients with postoperative anemia after total hip arthroplasty.
Postoperative anemia is a common complication after total hip arthroplasty (THA). However, the effect of edoxaban on postoperative anemia after THA remains unclear. Here, we retrospectively evaluated the clinical assessment of postoperative anemia and the associated changes of coagulation parameters in patients undergoing thromboprophylaxis with edoxaban compared with fondaparinux as a conventional anticoagulant thromboprophylactic agent after THA.. One hundred and forty-nine patients who underwent THA from July 2010 to June 2012 were divided into two groups, according to whether they were operated on before or after the approval of edoxaban: the fondaparinux group (Group F: 86 patients) and the edoxaban group (Group E: 63 patients). The frequency of postoperative anemia and blood coagulation values were investigated.. Postoperative anemia developed more frequently in Group E than in Group F after surgery. However, the degree of postoperative anemia showed no significant difference between the groups. Meanwhile, prothrombin time (PT), prothrombin time-international normalized ratio (PT-INR), and activated partial thromboplastin time were markedly higher in patients with edoxaban-associated postoperative anemia, which showed an increased potential to predict the occurrence of postoperative anemia. Additionally, both PT and PT-INR in Group E were also correlated with the volume of estimated blood loss.. The frequency of postoperative anemia was increased in patients treated with edoxaban, compared to fondaparinux, after THA. Edoxaban thromboprophylaxis might, therefore, require more careful monitoring to prevent postoperative anemia. Additionally, particular prolongation of PT and PT-INR induced by edoxaban treatment might predict postoperative anemia. Topics: Aged; Aged, 80 and over; Anemia; Anticoagulants; Arthroplasty, Replacement, Hip; Blood Coagulation Tests; Chemoprevention; Factor Xa Inhibitors; Female; Fondaparinux; Humans; Male; Middle Aged; Predictive Value of Tests; Pyridines; Retrospective Studies; Thiazoles; Venous Thromboembolism | 2018 |
Edoxaban, a direct factor Xa inhibitor, suppresses tissue-factor induced human platelet aggregation and clot-bound factor Xa in vitro: Comparison with an antithrombin-dependent factor Xa inhibitor, fondaparinux.
Tissue factor-induced platelet aggregation and factor Xa (FXa) activity bound to clot contribute to the formation and growth of thrombus. The effects of edoxaban, a direct FXa inhibitor, on these responses were determined and compared with that of fondaparinux, an antithrombin-dependent (indirect) FXa inhibitor.. Human platelet aggregation was induced by human tissue factor (Dade Innovin or RecombiPlasTin) in platelet-rich plasma spiked with edoxaban or fondaparinux. Clot formed from human whole blood was incubated with 0.9μM prothrombin in the absence or presence of FXa inhibitors. As the index of FXa activity, the amount of prothrombin fragment F1+2 was measured with an ELISA. Free FXa activity was measured using human FXa and its chromogenic substrate S-2222.. Edoxaban inhibited tissue factor-induced platelet aggregation in a concentration-dependent manner with the IC50 values of 150 and 110nM for Dade Innovin and RecombiPlasTin-induced platelet aggregation, respectively. At 1μM, edoxaban completely inhibited the aggregation. Fondaparinux inhibited RecombiPlasTin-induced aggregation with the IC50 of 9.3μM, but did not show complete inhibition up to 30μM and had no effect on Dade Innovin-induced aggregation. Edoxaban inhibited both free and clot-bound FXa with the IC50 of 2.3 and 8.2nM, respectively. Fondaparinux inhibited free FXa (IC50 5.4nM), but 40-times higher concentration were required to inhibit clot-bound FXa (IC50 217nM).. Edoxaban, a direct FXa inhibitor, was a more potent inhibitor of tissue factor-induced platelet aggregation and clot-bound FXa than fondaparinux, an indirect FXa inhibitor. Topics: Antithrombins; Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Factor Xa; Factor Xa Inhibitors; Female; Fondaparinux; Humans; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Polysaccharides; Pyridines; Thiazoles; Thromboplastin | 2016 |
Clinical Assessment of Postoperative Anemia Associated with Edoxaban in Patients Undergoing Total Knee Arthroplasty Compared to Fondaparinux.
Edoxaban, an oral direct factor Xa inhibitor, was developed and approved for anticoagulant thromboprophylaxis after total knee arthroplasty (TKA). We retrospectively investigated the postoperative anemia by oral administration of edoxaban 30 mg compared with fondaparinux 2.5 mg in TKA patients. Two hundred twenty nine patients who underwent TKA in National Hospital Organization Okayama Medical Center from July 2010 to June 2012 were divided into two groups; pre and post approval of edoxaban: fondaparinux-group (F-group) and edoxaban-group (E-group). As the primary endpoint, the frequency of postoperative anemia was evaluated. Blood coagulation values and relations between these parameters and postoperative anemia were also investigated. The frequency of postoperative anemia was significantly higher in E-group than F-group patients (52.7% vs. 37.8%; p<0.05). Hemoglobin (Hgb) levels were decreased with the peak at postoperative day (POD) 3 in both groups, and the change of Hgb values from POD1 (ΔHgb) was significantly increased in the E-group (p=0.04). At each POD, prothrombin time (PT) and international normalized ratio of PT (PT-INR) prolonged from the preoperative day in E-group were significantly higher than F-group. Additionally, PT and PT-INR in the E-group at POD3 were significantly prolonged in patients with postoperative anemia and the sensitivity of cut-off values to predict postoperative anemia was superior to the activated partial thromboplastin time (APTT). Thus, as the frequency of postoperative anemia tended to be higher in E-group, edoxaban 30 mg might require vigilance, and prolonged PT and PT-INR could potentially predict edoxaban-associated postoperative anemia after TKA. Topics: Administration, Oral; Aged; Aged, 80 and over; Anemia; Arthroplasty, Replacement, Knee; Factor Xa Inhibitors; Female; Fondaparinux; Humans; Injections, Subcutaneous; International Normalized Ratio; Male; Partial Thromboplastin Time; Polysaccharides; Postoperative Complications; Prothrombin Time; Pyridines; Thiazoles; Thrombosis | 2016 |
[Venous Thromboembolism during the Cisplatin-based Adjuvant Chemotherapy;Report of a Case].
We report a case of venous thromboembolism during the cisplatin-based adjuvant chemotherapy. A 49-year-old woman who was undergone left lower lobectomy for the lung cancer received adjuvant chemotherapy of cisplatin + vinorelbine ditartrate regimen. On day 11 after starting the chemotherapy, she presented a left lower leg pain and readmitted. Computed tomography revealed a deep venous thrombosis of the left lower leg and peripheral pulmonary embolism. The symptom and thromboembolism were successfully treated by anticoagulant drug and thrombolytic therapy. Although cisplatin-based chemotherapy is a risk factor of venous thromboembolism in patients with advanced malignancy, it should be also recognized as a complication of the adjuvant chemotherapy after surgery. Topics: Anticoagulants; Chemotherapy, Adjuvant; Cisplatin; Drug Substitution; Drug Therapy, Combination; Echocardiography; Female; Fibrinolytic Agents; Fondaparinux; Humans; Lung Neoplasms; Middle Aged; Polysaccharides; Pyridines; Thiazoles; Thrombolytic Therapy; Tomography, X-Ray Computed; Treatment Outcome; Urokinase-Type Plasminogen Activator; Venous Thromboembolism | 2016 |
Retrospective comparison of three thromboprophylaxis agents, edoxaban, fondaparinux, and enoxaparin, for preventing venous thromboembolism in total knee arthroplasty.
Patients undergoing total knee arthroplasty (TKA) are at high risk of venous thromboembolism, manifesting as deep vein thrombosis (DVT) or pulmonary embolism. The purpose of this study is to evaluate the efficacy and safety of edoxaban 15 mg once daily (o.d.) for preventing DVT in patients undergoing TKA.. Three hundred patients undergoing primary TKA under general anaesthesia for osteoarthritis were enrolled in this study: 100 treated with enoxaparin 2,000 IU twice daily (b.i.d.), 100 treated with fondaparinux 1.5 mg o.d. and 100 treated with edoxaban 15 mg o.d.. All treatments were scheduled to continue for 14 days.. The incidence of DVT in patients treated with edoxaban 15 mg o.d. was lower than in patients with enoxaparin 2,000 IU b.i.d. and fondaparinux 1.5 mg o.d.. D-dimer levels were significantly lower in patients with edoxaban than in patients with enoxaparin and fondaparinux 1.5 mg o.d. on the first postoperative day; ΔHb levels were lower in patients with edoxaban than in patients with enoxaparin and fondaparinux on postoperative days, However, the difference was not statistically significant. Finally, the incidence of hepatic dysfunction was lower in patients with edoxaban than in patients with enoxaparin and fondaparinux.. Edoxaban 15 mg o.d. was more efficient than enoxaparin 2,000 IU b.i.d. and fondaparinux 1.5 mg o.d.. Furthermore, edoxaban was safe compared with enoxaparin and fondaparinux. Edoxaban, an orally administered direct factor Xa (FXa) inhibitor, may offer a new option for preventing DVT, with a level of evidence III. Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Knee; Dose-Response Relationship, Drug; Enoxaparin; Female; Fondaparinux; Humans; Incidence; Knee Joint; Male; Osteoarthritis, Knee; Polysaccharides; Pyridines; Retrospective Studies; Thiazoles; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis | 2014 |
Treatment of venous thrombosis with an oral direct factor Xa inhibitor edoxaban by single and multiple administrations in rats.
Edoxaban is an oral and direct activated factor X inhibitor. In this study, the acute treatment effect of edoxaban on venous thrombosis is investigated in rats by single and multiple administrations, and compared to the conventional parenteral anticoagulants, enoxaparin and fondaparinux. Venous thrombus was induced in the inferior vena cava by partial stenosis plus topical application of 10% ferric chloride for 5min. After 1-h thrombus maturation, oral edoxaban and subcutaneous enoxaparin and fondaparinux were given. In the single administration experiment, thrombus weight was measured 1 or 4h after thrombus induction. In the multiple administration experiments, edoxaban was orally administered once daily (QD) and twice daily (BID) for 3 days. In the single administration experiment, oral administration of edoxaban (3.0 and 10mg/kg) 1h after thrombus formation significantly regressed the venous thrombus compared to the thrombus at 1h after thrombus formation. Similarly the significant venous thrombus regression was observed with enoxaparin (10mg/kg) and fondaparinux (0.30-3.0mg/kg). In the multiple administration experiment, both QD and BID administration of edoxaban at daily doses of 5 and 10mg/kg exerted significant treatment effects. QD administration of edoxaban including lower doses (1-10mg/kg) significantly reduced thrombus weight. Edoxaban administered QD and BID was effective in the treatment of venous thrombosis, and the treatment effect of edoxaban was comparable to the conventional parenteral anticoagulants. These data demonstrate the potential of edoxaban as an oral anticoagulant in the acute treatment of venous thromboembolism. Topics: Administration, Oral; Animals; Anticoagulants; Antithrombin III; Disease Models, Animal; Drug Administration Schedule; Enoxaparin; Factor Xa Inhibitors; Fondaparinux; Male; Peptide Hydrolases; Polysaccharides; Pyridines; Rats; Rats, Wistar; Thiazoles; Venous Thrombosis | 2014 |
Impact of antithrombin deficiency on efficacy of edoxaban and antithrombin-dependent anticoagulants, fondaparinux, enoxaparin, and heparin.
Oral factor Xa (FXa) inhibitors are a novel class of anticoagulants that, unlike heparins, are expected to demonstrate antithrombotic effects independent of plasma antithrombin (AT) concentrations. We utilized heterozygous AT-deficient (AT+/-) mice to determine the impact of AT deficiency on anticoagulant and antithrombotic effects of edoxaban, a direct FXa inhibitor, and compared with heparins (fondaparinux, enoxaparin, and unfractionated heparin [UHF]).. The effects of edoxaban and heparins on in vitro prothrombin time and activated partial thromboplastin time were measured in plasma obtained from wild type (AT+/+) and AT+/- male mice. To assess the antithrombotic effects of these anticoagulants in vivo, venous thrombosis was induced in the inferior vena cava by FeCl3 treatment. Potency ratios of antithrombotic effects in AT+/- compared with AT+/+ mice were analyzed by a parallel line assay.. In vitro studies demonstrated that the clotting-time prolongation effects of edoxaban were not affected by heterozygous AT deficiency whereas those of AT-dependent anticoagulants were attenuated. In AT+/- mice, the antithrombotic effects of AT-dependent anticoagulants were less potent than those in AT+/+ mice. In contrast, edoxaban was equipotent in preventing thrombus formation in both wild-type and AT-deficient mice. The attenuated antithrombotic effects of fondaparinux, enoxaparin, and UFH in AT-deficient mice were restored by AT supplementation. Edoxaban exerts a comparable antithrombotic effect even in mice with low plasma AT antigen and activity to that in wild-type mice.. Edoxaban may potentially be prioritized over AT-dependent anticoagulants in patients with lower plasma AT concentration. Topics: Animals; Anticoagulants; Antithrombin III; Blood Coagulation Tests; Enoxaparin; Factor Xa Inhibitors; Female; Fondaparinux; Gene Deletion; Hemostasis; Male; Mice; Mice, Inbred C57BL; Polysaccharides; Pyridines; Thiazoles; Venous Thrombosis | 2013 |
In vitro study of the anticoagulant effects of edoxaban and its effect on thrombin generation in comparison to fondaparinux.
Edoxaban, an oral direct factor Xa (FXa) inhibitor, is in Phase III development for prevention and treatment of thromboembolic disorders. Fondaparinux is an approved indirect FXa inhibitor. This study compared the effects of edoxaban and fondaparinux on thrombin generation (TG) using the calibrated automated thrombogram (CAT). Secondary objectives included evaluation of edoxaban and inhibition of coagulation parameters (prothrombin time [PT], activated partial thromboplastin time [aPTT]), anti-FXa activity and clotting times.. Pooled citrated platelet-poor plasma from healthy subjects was spiked with edoxaban (0.02-3.65 μM) or fondaparinux (0.15-1.18 μM). Parameters of TG were calculated using Thrombinoscope software. PT ratios and aPTT were measured in the presence of different thromboplastin reagents. Exogenous anti-FXa was measured using Rotachrom HBPM (Stago) and a specific assay developed for direct FXa inhibitors (Hyphen BioMed).. Edoxaban exhibited a 3-fold greater concentration-dependent effect than fondaparinux across TG parameters (except endogenous thrombin potential). Edoxaban also produced a concentration-dependent prolongation of PT ratio and aPTT. The magnitude of concentration-dependent increase was related to thromboplastin reagent. In contrast to edoxaban, fondaparinux was inactive on these clotting tests. Linear correlations were observed between plasma concentration of edoxaban and anti-FXa activity and results of clotting time assays.. TG evaluation by the CAT method, coagulation tests, and anti-FXa and clotting assays demonstrated concentration-dependent effects of edoxaban. The PT and aPTT prolongation are reagent dependent; correction of PT ratio by international normalized ratio does not reduce variability in response. The greater effect of edoxaban vs. fondaparinux may be related to the broader activity of direct FXa inhibitors compared with indirect FXa inhibitors. Topics: Anticoagulants; Blood Coagulation; Blood Platelets; Cells, Cultured; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Fondaparinux; Humans; In Vitro Techniques; Polysaccharides; Pyridines; Thiazoles; Thrombin | 2012 |
Comparison of antithrombotic efficacy between edoxaban, a direct factor Xa inhibitor, and fondaparinux, an indirect factor Xa inhibitor under low and high shear rates.
Edoxaban is an oral, direct factor Xa (FXa) inhibitor under late-phase clinical development. This study compared the antithrombotic efficacy of edoxaban with that of an indirect FXa inhibitor, fondaparinux, in in vivo venous and arterial thrombosis models and in ex vivo perfusion chamber thrombosis model under low and high shear rates in rats. Venous and arterial thrombi were induced by platinum wire insertion into the inferior vena cava and by application of FeCl₃ to the carotid artery, respectively. The perfusion chamber thrombus was formed by blood perfusion into a collagen-coated capillary at 150 s⁻¹ (low shear rate) and 1,600 s⁻¹ (high shear rate). Effective doses of edoxaban that reduced thrombus formation by 50% (ED₅₀) in venous and arterial thrombosis models were 0.076 and 0.093 mg/kg/h, respectively. In contrast, ED₅₀ of fondaparinux in the arterial thrombosis model (>10 mg/kg/h) was markedly higher compared to ED₅₀ in the venous thrombosis model (0.021 mg/kg/h). In the perfusion chamber thrombosis model, the ratio of ED₅₀ under high shear rate (1.13 mg/kg/h) to that under low shear rate (0.63 mg/kg/h) for edoxaban was 1.9, whereas that for fondaparinux was more than 66. While the efficacy of fondaparinux markedly decreased in arterial thrombosis and in a high-shear state, edoxaban exerted consistent antithrombotic effects regardless of flow conditions. These results suggest that shear rate is a key factor in different antithrombotic effects between edoxaban and fondaparinux. Topics: Animals; Anticoagulants; Antithrombins; Blood Flow Velocity; Carotid Arteries; Disease Models, Animal; Factor Xa Inhibitors; Fondaparinux; Humans; Male; Polysaccharides; Pyridines; Rats; Rats, Wistar; Thiazoles; Thrombosis; Vena Cava, Inferior | 2011 |