Effect of apixaban, an oral and direct factor Xa inhibitor, on coagulation activity biomarkers following acute coronary syndrome

2010 ◽  
Vol 104 (11) ◽  
pp. 976-983 ◽  
Author(s):  
John Alexander ◽  
L. Kristin Newby ◽  
Hongqiu Yang ◽  
Yuchen Barrett ◽  
Puneet Mohan ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Factor Xa ◽  
Factor Xa Inhibitor ◽  
Direct Factor ◽  
Coagulation Activity ◽  
Once Daily ◽  
St Segment Elevation ◽  
Coronary Syndrome ◽  
Daily Dose ◽  
D Dimer

SummaryApixaban is an oral, direct factor Xa inhibitor under development for secondary prevention in acute coronary syndrome (ACS). Apixaban‘s effect on D-dimer and prothrombin fragment 1.2 (F1.2) (coagulation activity biomarkers ) was determined in a randomised, double-blinded, placebo-controlled, phase 2 study. Patients (n=1,715) with either ST-segment elevation or non-ST-segment elevation ACS received either placebo or apixaban 2.5 mg twice daily, 10 mg once daily, 10 mg twice daily or 20 mg once daily for six months. Samples were obtained at baseline (before study drug administration), week 3 and week 26. Apixaban plasma concentrations were measured directly by liquid chromatography/mass spectometry, and anti-Xa activity was determined using apixaban as a reference standard. D-dimer and F 1.2 were measured using ELISA-based methods. Most patients had elevated D-dimer and F1.2 levels at baseline. Both coagulation activity biomarkers decreased by week 3 in all treatment groups, but to a greater degree with apixaban than placebo (p<0.001). In a multivariable analysis, apixaban was independently associated with a change in biomarkers over time (p<0.0001). While the overall decrease did not differ significantly among the three highest apixaban doses, F1.2 was suppressed more rapidly by the 10 mg once daily than the 2.5 mg twice daily dose (p<0.05). There was a strong and direct relationship between apixaban plasma concentrations and anti-Xa-apixaban levels, and an inverse relationship for both measures with coagulation activity biomarkers. In conclusion, the oral direct factor Xa inhibitor apixaban significantly reduced coagulation activity biomarkers among patients with ACS. The 10 mg once daily dose reduced thrombin generation (F 1.2) and fibrin formation (D-dimer) more rapidly and robustly than the 2.5 mg twice daily dose. The effect on both D-dimer and F 1.2 was apixaban concentration-and factor Xa inhibition dependent, durable and provided general guidance for dose selection in phase 3 investigation.

scholarly journals Factor Xa Inhibition Reduces Coagulation Activity but Not Inflammation Among People With HIV: A Randomized Clinical Trial

2020 ◽  
Vol 7 (2) ◽  
Author(s):  
Jason V Baker ◽  
Julian Wolfson ◽  
Tess Peterson ◽  
Micah Mooberry ◽  
Matthew Gissel ◽  
...  
Keyword(s):  
Immune Activation ◽  
Disease Risk ◽  
Substantial Reduction ◽  
Factor Xa ◽  
Factor Xa Inhibitor ◽  
Direct Factor ◽  
Bleeding Events ◽  
Double Blind ◽  
Coagulation Activity ◽  
D Dimer

Abstract Background Coagulation activity among persons with HIV is associated with end-organ disease risk, but the pathogenesis is not well characterized. We tested a hypothesis that hypercoagulation contributes to disease risk, in part, via upregulation of inflammation. Methods Treatment effects of edoxaban (30 mg), a direct factor Xa inhibitor, vs placebo were investigated in a randomized, double-blind crossover trial among participants with HIV and viral suppression and D-dimer levels ≥100 ng/mL. During each 4-month crossover period, blood measures of coagulation, inflammation, and immune activation were assessed. Analyses of change on edoxaban vs change on placebo used linear mixed models. Results Forty-four participants were randomized, and 40 completed at least 1 visit during each study period. The mean age was 49 years, and the CD4+ count was 739 cells/mm3. Edoxaban treatment led to declines in D-dimer (44%) and thrombin-antithrombin complex (26%) but did not lower inflammatory or immune activation measures. More bruising or bleeding events occurred during edoxaban (n = 28) than during placebo or no drug periods (n = 15). Conclusions The direct factor Xa inhibitor edoxaban led to a substantial reduction in coagulation but no effect on inflammation or immune activation. These results do not support that hypercoagulation contributes to ongoing inflammation during chronic antiretroviral therapy–treated HIV disease.

Assessment of laboratory assays to measure rivaroxaban – an oral, direct factor Xa inhibitor

2010 ◽  
Vol 103 (04) ◽  
pp. 815-825 ◽  
Author(s):  
Jean-Luc Martinoli ◽  
Léna LeFlem ◽  
Céline Guinet ◽  
Geneviève Plu-Bureau ◽  
François Depasse ◽  
...  
Keyword(s):  
Vitamin K Antagonists ◽  
Plasma Concentrations ◽  
Factor Xa ◽  
Specific Factor ◽  
Factor Xa Inhibitor ◽  
Direct Factor ◽  
Paradoxical Response ◽  
Pharmacodynamic Effects ◽  
Dependent Relationship ◽  
Low Concentrations

SummaryAlthough there is no need for routine coagulation monitoring with rivaroxaban – an oral, direct factor Xa inhibitor – a haemostasis assay might be valuable to measure its pharmacodynamic effects. This study aimed to find assays, among those commercially available, to measure rivaroxaban pharmacodynamics. Several global conventional clotting tests, as well as clotting or chromogenic assays to measure anti-factor Xa activity, were studied. A thrombin generation test using calibrated automated thrombogram was also done. Tests were performed with the indirect factor Xa inhibitor fondaparinux for comparison. A concentration-dependent prolongation of prothrombin time (PT), dilute PT, and activated partial thromboplastin time was observed with rivaroxaban. The results varied depending on the reagents. This variability cannot be standardised with the international normalised ratio system commonly used for vitamin K antagonists. Using a standard calibration curve, PT test results can be expressed in plasma concentrations of rivaroxaban rather than PT seconds or ratio. Standard methods for HepTest and two-step prothrombinase-induced clotting time (PiCT) resulted in a paradoxical response, with low concentrations of rivaroxaban reducing clotting times. This was not observed with shorter incubation times, or when antithrombin-deficient (immunodepleted) plasma was used. The chromogenic tests found a dose-dependent relationship between anti-factor Xa activity and rivaroxaban concentration. Modified specific factor Xa chromogenic assays are being further investigated. One-step PiCT and HepTest with shortened incubation times, as well as the widely available PT assay (using a rivaroxaban calibrator) could be useful to monitor the pharmacodynamic effects of rivaroxaban accurately. Finally, all clotting and chromogenic assays showed a concentration-dependent effect induced by rivaroxaban.

Anti–Factor Xa Activity of Fixed-Dose Fondaparinux in Low-Body-Weight Patients With Acute Coronary Syndrome

2020 ◽  
Vol 54 (11) ◽  
pp. 1083-1089
Author(s):  
Wanwarang Wongcharoen ◽  
Nualnit Tantisirivit ◽  
Lalita Norasetthada ◽  
Siriluck Gunaparn ◽  
Arintaya Phrommintikul
Keyword(s):  
Acute Coronary Syndrome ◽  
Body Weight ◽  
Subcutaneous Injection ◽  
Bleeding Event ◽  
Factor Xa ◽  
Fixed Dose ◽  
Once Daily ◽  
St Segment Elevation ◽  
Coronary Syndrome ◽  
St Segment

Background: Fixed-dose 2.5 mg of fondaparinux subcutaneous injection once daily has been recommended in treatment of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) irrespective of body weight (BW). However, data on anti–factor Xa (anti-FXa) activity of fondaparinux are scarce in low-BW patients. Objective: We aimed to assess anti-FXa activity of fondaparinux in low-BW patients (BW < 50 kg) compared with normal-BW patients (BW ≥ 50 kg) who presented with NSTE-ACS. Methods: This is a prospective cohort study of patients with NSTE-ACS receiving fondaparinux. Anti-FXa activity was measured 4 hours after 2.5 mg subcutaneous injection of fondaparinux after the first 2 doses. Results: Among 87 enrolled patients, 18 (21%) had BW <50 kg. Patients in the low-BW group were older and had lower creatinine clearance. Median duration of fondaparinux therapy was 3 (IQR 2-4) days. Anti-FXa activity after the first dose of fondaparinux was similar between the low-BW and normal-BW groups (0.40 ± 0.15 vs 0.40 ± 0.17 mg/L, P = 0.914). However, anti-FXa activity after the second dose of fondaparinux was significantly higher in the low-BW group as compared with the normal-BW group (0.53 ± 0.10 vs 0.44 ± 0.16 mg/L, P = 0.011). Multivariate analysis showed that BW was the only independent factor that inversely correlated with anti-FXa activity. There was only 1 bleeding event during hospitalization in the normal-BW group and none in the low-BW group. Conclusion and Relevance: Anti-FXa activity of the second dose of fondaparinux was higher in low-BW patients but still within the expected range.

scholarly journals A Once-Daily, Oral, Direct Factor Xa Inhibitor, Rivaroxaban (BAY 59-7939), for Thromboprophylaxis After Total Hip Replacement

Circulation ◽  
2006 ◽  
Vol 114 (22) ◽  
pp. 2374-2381 ◽  
Author(s):  
Bengt I. Eriksson ◽  
Lars C. Borris ◽  
Ola E. Dahl ◽  
Sylvia Haas ◽  
Menno V. Huisman ◽  
...  
Keyword(s):  
Total Hip Replacement ◽  
Hip Replacement ◽  
Factor Xa ◽  
Factor Xa Inhibitor ◽  
Direct Factor ◽  
Once Daily ◽  
Total Hip

Pharmacokinetics, Biotransformation, and Mass Balance of Edoxaban, a Selective, Direct Factor Xa Inhibitor, in Humans

2012 ◽  
Vol 40 (12) ◽  
pp. 2250-2255 ◽  
Author(s):  
Mohinder S. Bathala ◽  
Hiroshi Masumoto ◽  
Toshihiro Oguma ◽  
Ling He ◽  
Chris Lowrie ◽  
...  
Keyword(s):  
Mass Balance ◽  
Factor Xa ◽  
Factor Xa Inhibitor ◽  
Direct Factor

Betrixaban – the next direct factor Xa inhibitor?

2016 ◽  
Vol 9 (12) ◽  
pp. 1111-1117 ◽  
Author(s):  
Martin Thoenes ◽  
Joan Minguet ◽  
Karin Bramlage ◽  
Peter Bramlage ◽  
Carmen Ferrero
Keyword(s):  
Factor Xa ◽  
Factor Xa Inhibitor ◽  
Direct Factor

scholarly journals In vitro and in vivo studies of the novel antithrombotic agent BAY 59-7939-an oral, direct Factor Xa inhibitor

2005 ◽  
Vol 3 (3) ◽  
pp. 514-521 ◽  
Author(s):  
E. PERZBORN ◽  
J. STRASSBURGER ◽  
A. WILMEN ◽  
J. POHLMANN ◽  
S. ROEHRIG ◽  
...  
Keyword(s):  
Factor Xa ◽  
In Vivo Studies ◽  
Factor Xa Inhibitor ◽  
The Novel ◽  
Direct Factor ◽  
Antithrombotic Agent

Evaluation of the Use of Low-Dose 4-Factor Prothrombin Complex Concentrate in the Reversal of Direct Oral Anticoagulants in Bleeding Patients

2018 ◽  
Vol 35 (9) ◽  
pp. 903-908 ◽  
Author(s):  
Teresa A. Allison ◽  
Pei Jen Lin ◽  
Jennifer A. Gass ◽  
Kenneth Chong ◽  
Samuel J. Prater ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Prothrombin Complex Concentrate ◽  
Low Dose ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Final Analysis ◽  
Factor Xa Inhibitor ◽  
Direct Factor

Objective: This study investigated the percentage of patients who achieved hemostasis with 4-factor prothrombin complex concentrate (4-factor PCC) 35 U/kg. The primary end point was to determine the effect of 4-factor PCC 35 U/kg on bleeding progression, assessed using computed tomography. Methods: This was a retrospective, observational, single-center study conducted in patients with a major bleed admitted to a level 1 trauma center from May 1, 2013, to June 15, 2015, who received 4-factor PCC 35 U/kg for reversal of a direct factor Xa inhibitor taken prior to admission. Results: Thirty-three patients were included in the study, with 31 patients in the final analysis. The mean (standard deviation) age was 73 (14.8) years; 54.5% of patients were female. Of the 33 patients, 13 presented with a traumatic brain injury, 9 with an aneurysmal subarachnoid hemorrhage, 8 with an intracerebral hemorrhage, 1 with a gastrointestinal bleed, 1 with a hematoma with active extravasation, and 1 with an intra-abdominal bleed. The most frequently used direct factor Xa inhibitor was rivaroxaban (81.8%). Overall, 83.8% of patients achieved hemostasis with 4-factor PCC 35 U/kg. Progression of hemorrhage was observed in 4 patients on repeat computed tomography scan and 1 patient had continued surgical bleeding. No thromboembolic events were reported. Conclusions: Low-dose, 4-factor PCC 35 U/kg appeared to produce hemostasis in a majority of the patients. This may be an effective dosing regimen for anticoagulant reversal of factor Xa inhibitors in clinically bleeding patients.

scholarly journals Identification of ssDNA specific to a direct factor Xa inhibitor

2020 ◽  
Author(s):  
Ka Lok Hong ◽  
Nevina Trunzo ◽  
Mina Roueinfar ◽  
Kiersten B. Wiedwald ◽  
Julia Iskra ◽  
...  
Keyword(s):  
Factor Xa ◽  
Factor Xa Inhibitor ◽  
Direct Factor
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