Idarucizumab, a Humanized, Monoclonal Antibody Fragment for Immediate Reversal of Dabigatran

2015 ◽  
Vol 28 (6) ◽  
pp. 548-554 ◽  
Author(s):  
Marta A. Miyares ◽  
Yara Kuyumjian ◽  
Shannon Eaves ◽  
Eliza Dollard
Keyword(s):  
Monoclonal Antibody ◽  
Anticoagulant Activity ◽  
Antibody Fragment ◽  
The United States ◽  
Mesh Term ◽  
Priority Review ◽  
Reversal Agent ◽  
Humanized Monoclonal Antibody ◽  
Pubmed Database ◽  
License Application

Objective: To evaluate the role of idarucizumab, a humanized monoclonal antibody fragment, as a specific reversal agent for the anticoagulant activity of dabigatran and to review the pharmacology, pharmacokinetic properties, efficacy, and safety of this agent. Methods: A literature search was conducted consisting of a PubMed database using the MeSH term idarucizumab and the key word dabigatran antidote. Studies evaluating the pharmacology, pharmacokinetics, safety, and efficacy of idarucizumab for the reversal of the anticoagulant activity of dabigatran were included. Results: Idarucizumab represents a novel treatment option as it is the only humanized, monoclonal antibody fragment that specifically binds to dabigatran. Studies evaluating reversal of dabigatran-induced anticoagulation have demonstrated immediate, complete, and sustained effects with idarucizumab. Idarucizumab did not overcorrect thrombin generation. Additionally, evaluations have shown that dabigatran can be safely reinitiated 24 hours after the administration of idarucizumab. The United States Food and Drug Administration granted priority review for the biologic license application and accelerated approval for idarucizumab. Conclusion: Idarucizumab represents an encouraging development in the reversal of dabigatran. Its novel mechanism of action, pharmacokinetics, tolerability, and lack of thrombotic events contribute positively to its use in patients who experience bleeding or for those who require emergent surgery or procedures.

scholarly journals Genetic Polymorphisms Affecting Ranibizumab Response in High Myopia Patients

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1973
Author(s):  
David Blánquez-Martínez ◽  
Xando Díaz-Villamarín ◽  
Alba Antúnez-Rodríguez ◽  
Ana Pozo-Agundo ◽  
José Ignacio Muñoz-Ávila ◽  
...  
Keyword(s):  
Genetic Polymorphisms ◽  
Genetic Variants ◽  
High Myopia ◽  
Antibody Fragment ◽  
The United States ◽  
Vascular Endothelial ◽  
Humanized Monoclonal Antibody ◽  
Ophthalmic Pathology ◽  
Endothelial Growth Factor ◽  
Vegfa Gene

High myopia is an ophthalmic pathology that affects half of the young adults in the United States and Europe and it is predicted that a third of the world’s population could be nearsighted at the end of this decade. It is characterized by at least 6 diopters or axial length > 26 mm and, choroidal neovascularization (CNV) in 5 to 11% of cases. Ranibizumab is a recombinant humanized monoclonal antibody fragment. It is an anti-vascular endothelial growth factor (anti-VEGF) drug used in the treatment of CNV. Many genetic polymorphisms have been associated with interindividual differences in the response to ranibizumab, but these associations were not yet assessed among patients with high myopia and CNV. We performed a retrospective study assessing the association of genetic polymorphisms with response to ranibizumab in patients with CNV secondary to high myopia (mCNV). We included genetic polymorphisms previously associated with the response to drugs used in CNV patients (bevacizumab, ranibizumab, aflibercept, and photodynamic therapy (PDT)). We also included genetic variants in the VEGFA gene. Based on our results, ARMS2 (rs10490924) and CFH (rs1061170) are associated with response to ranibizumab in high myopia patients; and, included VEGFA genetic polymorphisms are not associated with ranibizumab response in our population but might be related to a higher risk of CNV.

scholarly journals A dabigatran-antidótum, az intravénás idarucizumab első hazai alkalmazása

2017 ◽  
Vol 158 (10) ◽  
pp. 387-392 ◽  
Author(s):  
Lajos Driesz ◽  
Éva Barabás ◽  
Ildikó Bodócs ◽  
Zoltán Szántó ◽  
György Herr ◽  
...  
Keyword(s):  
Stroke Risk ◽  
Surgical Intervention ◽  
Antibody Fragment ◽  
Thrombin Inhibitor ◽  
The Novel ◽  
Reversal Agent ◽  
Humanized Monoclonal Antibody ◽  
Life Threatening ◽  
Direct Anticoagulants ◽  
Emergency Cholecystectomy

Abstract: At present, the direct thrombin inhibitor dabigatran is the only one amongst the new direct anticoagulants which has an effective, specific reversal agent. The novel agent idarucizumab is a humanized, monoclonal antibody fragment binds to dabigatran within minutes thereby offers an opportunity to induce a safe, long-lasting reverse of the anticoagulant effects of dabigatran. The authors describe the first use of idarucizumab in Hungary (23. 05. 2016) in an old female patient with non-valvular paroxysmal atrial fibrillation of high stroke risk-score and renal dysfunction who was taking dabigatran (2 x 110 mg/day) when an acute abdomen developed requiring emergency cholecystectomy. Patient received the antidote (idarucizumab 2 x 2.5 g/50 ml iv.) two hours before the surgical intervention, and she did not have any uncontrollable, life-threatening bleeding during the surgery. The high activated partial thromboplastin time relating to anticoagulative influence before the surgery normalized completely after administration of the antidote. Antagonizing dabigatran with idarucizumab was feasible and safe without any side effects. The patient received dabigatran therapy again after her recovery. Orv. Hetil., 2017, 158(10), 387–392.

scholarly journals DABIGATRAN AND IDARUZIZUMAB. NEW OPPORTUNITIES FOR IMPROVING PATIENT SAFETY

2019 ◽  
pp. 53-61
Author(s):  
N. A. Novikova ◽  
A. N. Volovchenko ◽  
D. A. Parfenov
Keyword(s):  
Monoclonal Antibody ◽  
Clinical Trials ◽  
Clinical Practice ◽  
Oral Anticoagulants ◽  
Medication Use ◽  
Antibody Fragment ◽  
Efficacy And Safety ◽  
Reversal Agent ◽  
Reversal Agents ◽  
Real Clinical Practice

The widespread use of new oral anticoagulants in clinical practice requires improving the safety of medication use, i.e. the use of specific reversal agents, if necessary. Idarucizumab, a humanied monoclonal antibody fragment, is the first reversal agent authorized in our country that binds to dabigatran. Its efficacy and safety have been validated in several clinical trials, and its use gains experience in real clinical practice.

scholarly journals The preoperative management of dabigatran and its specific antidote idarucizumab in patients with nonvalvular atrial fibrillation: Case reports

2020 ◽  
Vol 70 (5) ◽  
pp. 310-318
Author(s):  
Milan Tomić
Keyword(s):  
Atrial Fibrillation ◽  
Anticoagulant Activity ◽  
Case Reports ◽  
Oral Anticoagulants ◽  
Antibody Fragment ◽  
Bleeding Risk ◽  
Ease Of Use ◽  
Preoperative Management ◽  
Nonvalvular Atrial Fibrillation ◽  
Reversal Agent

Dabigatran is a novel oral anticoagulant preferred due to its ease of use, favorable pharmacokinetics, decreased potential for drug-drug interactions, and the lack of monitoring requirements. With the growing use of dabigatran, it is important to highlight that dabigatran increases the risk of hemorrhage after some procedures. Therefore, when dabigatran is used before the elective or urgent procedures, it is necessary to compare the thromboembolic event risk with the relative risk of bleeding. Before the approval of a reversal agent, the lack of specific antidotes had been the major limitation against the widespread utilization of dabigatran. In October 2015, idarucizumab, a humanized monoclonal antigen-binding antibody fragment capable of reversing the anticoagulant activity of dabigatran, has been introduced into the market to be used in lifethreatening bleeding or urgent surgery. In this manuscript, the preoperative management of dabigatran and the initial experience of using idarucizumab in a patient with nonvalvular atrial fibrillation were described. We propose that the option of dabigatran reversal needs to be considered in patients with nonvalvular atrial fibrillation. However, additional research is needed to define optimal perioperative management of dabigatran and other novel oral anticoagulants, especially in high bleeding risk patients, and to determine whether pre-procedure coagulation testing should be performed.

scholarly journals Idarucizumab, a humanized monoclonal antibody fragment, for reversal of Dabigatran therapy for atrial fibrillation

2017 ◽  
Vol 1 (1) ◽  
Author(s):  
Osmar Antonio Centurión ◽  
Nelson Javier Aquino ◽  
Laura Beatriz García ◽  
Judith María Torales
Keyword(s):  
Atrial Fibrillation ◽  
Monoclonal Antibody ◽  
Antibody Fragment ◽  
Humanized Monoclonal Antibody ◽  
Dabigatran Therapy

Idarucizumab for Urgent Dabigatran Reversal in Clinical Practice: A Case Series of First Use in Vietnam

MedPharmRes ◽  
2020 ◽  
Vol 4 (1) ◽  
pp. 13-17
Author(s):  
Sy Van Hoang ◽  
Kha Minh Nguyen
Keyword(s):  
Monoclonal Antibody ◽  
Clinical Practice ◽  
Vitamin K ◽  
Oral Anticoagulants ◽  
Case Series ◽  
Antibody Fragment ◽  
Randomized Control Trials ◽  
Humanized Monoclonal Antibody ◽  
Life Threatening ◽  
Randomized Control

The benefits of non-Vitamin K oral antagonists in prevention or treatment of thrombosis have been studied in many randomized control trials. However, episodes of life-threatening bleeding caused by using novel oral anticoagulants have occurred in clinical practice and necessitate the development of aims for reversal of the anticoagulant effects. We report here three cases in which the use of idarucizumab, a humanized monoclonal antibody fragment, has successfully reversed the anticoagulation effects of dabigatran and produced favorable outcomes.

Questions to the Article: A Global Overview of COVID-19 Research in the Pediatric Field (Preprint)

2021 ◽  
Author(s):  
CHIEN WEI ◽  
Julie Chi Chow ◽  
Willy Chou
Keyword(s):  
The United States ◽  
Mesh Term ◽  
Forest Plot ◽  
Medical Subject Headings ◽  
Mesh Terms ◽  
Pubmed Database ◽  
The Us ◽  
Choropleth Maps ◽  
The Difference ◽  
Choropleth Map

UNSTRUCTURED The article, published on 23 July 2021, is well-written and of interest, but remains several questions that are required for clarifications, such as (1) the static choropleth map of collaboration analysis between countries should be dynamically visualized and highlighted by top three countries on their publications and author collaboration characteristics; (2) the research achievements in authors, institutes, and countries should be quantified by author-weighted scheme considering author order in article bylines; and (3) keyword analysis was too simple to identify the difference in article types between countries. We downloaded 2,268 abstracts from the Pubmed database with a search string of (COVID-19[MeSH Major Topic]) AND (pediatrics[Affiliation]), similar to the mentioned study, and displayed (1) choropleth maps highlighted by the most productive and highly author-collaborated countries, and (2)forest plot to identify differences in article types between two countries. The medical subject headings(MeSH terms) were used to denote the article types in articles. We observed that (1) three top productive countries were the United States, Italy, and India; (2) three top countries collaborated the authors affiliated with the US were Canada, the United Kingdom, and Italy; and (3) only the MeSH term of epidemiology presents the difference in article types between the US and India when the top 10 most frequently occurred MeSH terms were compared. We produced the dashboard-type visualizations to provide valuable information for readers. The novel visual representations make data clear with a better understanding of bibliographic analysis. The methods used in this study are recommended for future studies, not just limited to the field of COVID-19 research.

The Anticoagulant Properties of a Modified Form of Protein S

1988 ◽  
Vol 60 (02) ◽  
pp. 298-304 ◽  
Author(s):  
C A Mitchell ◽  
S M Kelemen ◽  
H H Salem
Keyword(s):  
Monoclonal Antibody ◽  
Anticoagulant Activity ◽  
Activated Protein C ◽  
Factor Xa ◽  
Protein S ◽  
Human Neutrophil Elastase ◽  
Factor X ◽  
Sds Page

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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