d-Phenylglycinol-derived non-covalent factor Xa inhibitors: Effect of non-peptidic S4 linkage elements on affinity and anticoagulant activity

2007 ◽  
Vol 17 (21) ◽  
pp. 5801-5805 ◽  
Author(s):  
Valentine J. Klimkowski ◽  
Brian M. Watson ◽  
Michael R. Wiley ◽  
John Liebeschuetz ◽  
Jeffry B. Franciskovich ◽  
...  
2017 ◽  
Vol 15 (4) ◽  
pp. 237-245 ◽  
Author(s):  
Tarek Nafee ◽  
Aysha Aslam ◽  
Gerald Chi ◽  
Seyedmahdi Pahlavani ◽  
Dima Nimri ◽  
...  

2021 ◽  
Author(s):  
Burcu TUNCAY ◽  
Selma Ari ◽  
Hasan Ari ◽  
Sencer CAMCI ◽  
Mehmet MELEK ◽  
...  

Abstract Objective:The aim of this study is to evaluate the effect of iohexol as a contrast agent on the anticoagulant activity of oral factor Xa inhibitors. Methods:The study included 65 people who underwent contrast computerized tomography (CT). Patients in group 1 were using rivaroxaban (20 patients), patients in group 2 were using apixaban (20 patients), patients in group 3 were using edoxaban (20 patients), and group 4 was the control group (5 volunteers). Iohexol (60ml) was used as a contrast agent. Two tubes were used to collect 2 ml of blood from the patients at 4 hours after the drug dose (rivaroxaban, apixaban, or edoxaban) and 1 hour after the contrast CT (CT was performed 3 hours after the drug was taken). In the control group, at any time and 1 hour after contrast CT, 2 tubes of 2 ml of blood were collected. The anticoagulant properties of rivaroxaban, apixaban, and edoxaban were evaluated using anti-factor Xa levels. Results:The anti-factor Xa level was increased after using the contrast agent in the rivaroxaban group (0.66±0.32U/ml vs. 0.67±0.32U/ml; p=0.01) and the edoxaban group (0.74±0.35 U/ml vs. 0.76±0.36 U/ml; p=0.006). However, there was no significant difference in the apixaban group (0.66±0.33U/ml vs. 0.66±0.32U/ml; p=0.21) and control group (0.02±0.01U/ml vs. 0.03±0.01U/ml; p=0.33).Conclusion:The anticoagulant properties of rivaroxaban and edoxaban tended to increase significantly, but there was no statistically significant difference in the anticoagulant properties of apixaban with contrast agent. The increasing is too small so that these laboratory results need to validate with larger clinical trials(NCT04611386).


2018 ◽  
Vol 51 (11) ◽  
pp. 975-979 ◽  
Author(s):  
S. M. Medvedeva ◽  
A. Yu. Potapov ◽  
I. V. Gribkova ◽  
E. V. Katkova ◽  
V. B. Sulimov ◽  
...  

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S17-S18
Author(s):  
Zahra Alipour ◽  
Ronald Jackups

Abstract Introduction Andexanet alfa, a reversal agent for factor Xa inhibitors rivaroxaban and apixaban, was approved by the Food and Drug Administration in May 2018 for patients with life-threatening bleeding. It acts by competing with endogenous factor Xa to block anticoagulant activity. Intravenous administration rapidly reduces anti-factor Xa activity. Because andexanet became available only recently, there is high potential for inappropriate use. Our objective was to investigate utilization and laboratory monitoring of andexanet in our hospital system in order to improve utilization. Methods This is a retrospective study with review of charts in the electronic medical record from April 2019 to February 2020. Charts were reviewed for the time of andexanet administration, anti-factor Xa testing before and after administration, turnaround time (TAT) for anti-factor Xa testing, and patient’s status after treatment. Results We identified 33 patients who received andexanet in our hospital system. Intracranial hemorrhage was the most common clinical symptom. Of 33 patients, 12 patients (36%) expired, one transferred to hospice, 18 (55%) were discharged alive, and two recent cases are alive awaiting disposition. Only 12 patients (36%) had anti-factor Xa testing performed prior to administration of andexanet, with one additional patient receiving testing only after administration. Factor Xa activity was misordered for anti-factor Xa in one patient. TAT for anti-factor Xa in these patients ranged from 25–112 minutes, with median 35.5 minutes. Of the 12 patients who had anti-factor Xa testing prior to administration, 4 expired and 8 survived. Pre-administration anti-factor Xa activity was significantly lower in patients who expired than in patients who survived (0.3 vs. 1.8 IU/ml, P value = 0.02). Conclusion Currently, anti-factor Xa testing is not ordered for most patients receiving andexanet alfa in our hospital system. Although not necessary for dosing decisions, anti-factor Xa testing may be useful prior to administration to identify patients unlikely to benefit from anticoagulant reversal. Despite a small sample size, there was a statistically significant difference in anti-factor Xa activity by patient outcome, suggesting that andexanet may be unhelpful in patients with low anti-factor Xa activity. Based on these findings, we are building an electronic order set to facilitate proper administration of this medication.


1991 ◽  
Vol 66 (04) ◽  
pp. 453-458 ◽  
Author(s):  
John T Brandt

SummaryLupus anticoagulants (LAs) are antibodies which interfere with phospholipid-dependent procoagulant reactions. Their clinical importance is due to their apparent association with an increased risk of thrombo-embolic disease. To date there have been few assays for quantifying the specific activity of these antibodies in vitro and this has hampered attempts to purify and characterize these antibodies. Methods for determining phospholipid-dependent generation of thrombin and factor Xa are described. Isolated IgG fractions from 7 of 9 patients with LAs were found to reproducibly inhibit enzyme generation in these assay systems, permitting quantitative expression of inhibitor activity. Different patterns of inhibitory activity, based on the relative inhibition of thrombin and factor Xa generation, were found, further substantiating the known heterogeneity of these antibodies. These systems may prove helpful in further purification and characterization of LAs.


1988 ◽  
Vol 60 (02) ◽  
pp. 298-304 ◽  
Author(s):  
C A Mitchell ◽  
S M Kelemen ◽  
H H Salem

SummaryProtein S (PS) is a vitamin K-dependent anticoagulant that acts as a cofactor to activated protein C (APC). To date PS has not been shown to possess anticoagulant activity in the absence of APC.In this study, we have developed monoclonal antibody to protein S and used to purify the protein to homogeneity from plasma. Affinity purified protein S (PSM), although identical to the conventionally purified protein as judged by SDS-PAGE, had significant anticoagulant activity in the absence of APC when measured in a factor Xa recalcification time. Using SDS-PAGE we have demonstrated that prothrombin cleavage by factor X awas inhibited in the presence of PSM. Kinetic analysis of the reaction revealed that PSM competitively inhibited factor X amediated cleavage of prothrombin. PS preincubated with the monoclonal antibody, acquired similar anticoagulant properties. These results suggest that the interaction of the monoclonal antibody with PS results in an alteration in the protein exposing sites that mediate the observed anticoagulant effect. Support that the protein was altered was derived from the observation that PSM was eight fold more sensitive to cleavage by thrombin and human neutrophil elastase than conventionally purified protein S.These observations suggest that PS can be modified in vitro to a protein with APC-independent anticoagulant activity and raise the possibility that a similar alteration could occur in vivo through the binding protein S to a cellular or plasma protein.


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