scholarly journals Andexanet Alfa for Specific Anticoagulation Reversal in Patients with Acute Bleeding during Treatment with Edoxaban

2022 ◽  
Author(s):  
Alexander P. Benz ◽  
Lizhen Xu ◽  
John W. Eikelboom ◽  
Saskia Middeldorp ◽  
Truman J. Milling ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Thrombotic Event ◽  
Acute Bleeding ◽  
Anticoagulation Reversal ◽  
Limited Experience ◽  
Life Threatening ◽  
Antifactor Xa ◽  
Andexanet Alfa ◽  
Uncontrolled Bleeding ◽  
Efficacy Population

Abstract Background Andexanet alfa (andexanet) is approved for specific anticoagulation reversal in patients with life-threatening or uncontrolled bleeding during treatment with rivaroxaban or apixaban. There is limited experience with andexanet in patients with acute bleeding on edoxaban. Methods Patients with acute major bleeding within 18 hours of edoxaban intake were prospectively enrolled. Patients received a bolus and 2-hour follow-on infusion of andexanet. The co-primary efficacy outcomes were change in antifactor Xa activity and the percentage of patients achieving excellent or good hemostasis, 12 hours after andexanet treatment. Efficacy was analyzed in patients with confirmed major bleeding and baseline antifactor Xa activity ≥40 ng/mL. Safety was analyzed in all patients. Results Thirty-six patients (mean age: 82 years, 61.1% male and 91.7% with atrial fibrillation) with acute major bleeding on edoxaban received andexanet. The primary site of bleeding was intracranial in 29 patients (80.6%). In the efficacy population (n = 28), median antifactor Xa activity decreased from 121.1 (interquartile range [IQR]: 70.3–202.4) ng/mL at baseline to 24.0 (IQR: 77.7–83.7) ng/mL at the end of andexanet bolus (median decrease: 68.9%, 95% confidence interval [CI]: 56.1–77.7%). Excellent or good hemostasis at 12 hours was achieved in 78.6% (95% CI: 59.0–91.7%) of patients. Within 30 days, four patients (11.1%) experienced a thrombotic event and four others (11.1%) died. Conclusion In patients with acute major bleeding on edoxaban, andexanet significantly decreased antifactor Xa activity. Hemostatic efficacy was similar to that observed in patients with bleeding on rivaroxaban or apixaban. Thrombotic events occurred at a rate expected in such patients.

Abstract P3: Andexanet Alfa for Acute Bleeding During Treatment With Edoxaban

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Alexander P Benz ◽  
Lizhen Xu ◽  
John W Eikelboom ◽  
Saskia Middeldorp ◽  
Truman J Milling ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Additional Data ◽  
Thrombotic Event ◽  
Factor Xa ◽  
Acute Bleeding ◽  
Study Enrollment ◽  
Inhibitor Study ◽  
Andexanet Alfa ◽  
Adjudication Committee ◽  
Efficacy Population

Introduction: We previously reported results of a prospective cohort study evaluating andexanet alfa (andexanet) for anticoagulation reversal in patients with acute bleeding on a factor Xa inhibitor. Study enrollment continued to accumulate additional data on patients on edoxaban, which are presented here. Methods: Patients with acute major bleeding within 18 hours of edoxaban intake were prospectively enrolled. Patients received a 400 or 800 mg bolus and a 480 or 960 mg 2-hour follow-on infusion of andexanet, depending on edoxaban dosage and time of last dose. The co-primary efficacy outcomes were change in anti-factor Xa activity and the rate of excellent or good hemostasis, 12 hours after andexanet treatment, as determined by an independent adjudication committee. Efficacy was analyzed in patients with confirmed major bleeding and baseline anti-factor Xa activity ≥75 ng/mL. Safety was analyzed in all patients. Results: A total of 36 patients (mean age 82 years, 61.1% male and 91.7% with atrial fibrillation) with acute major bleeding on edoxaban received andexanet. The primary site of bleeding was intracranial in 29 (80.6%) patients. In the efficacy population (n=20), median anti-factor Xa activity decreased from 160.5 (interquartile range [IQR] 106.2-222.2) ng/mL at baseline to 50.9 (IQR 19.9-119.4) ng/mL at the end of bolus (median decrease 69.2%, 95% confidence interval [CI] 25.5-80.2%). Excellent or good hemostasis at 12 hours was achieved in 75.0% (95% CI 50.9-91.3%) of patients overall and in 81.3% (95% CI 54.4-96.0%) of those with intracranial hemorrhage (ICH). Within 30 days, a total of 4 (11.1%) patients experienced at least one thrombotic event and 4 (11.1%) others died. Conclusions: In patients with acute bleeding on edoxaban, andexanet significantly decreased anti-factor Xa activity. Excellent or good hemostasis at 12 hours was observed in 75.0% of patients overall and 81.3% of those with ICH. Thrombotic events occurred at a rate expected in such patients.

A Review on the Use of Reversal Agents of Direct Oral Anticogulant Drugs in Case of Gastrointestinal Bleeding

2020 ◽  
Vol 15 ◽  
Author(s):  
Veronica Ojetti ◽  
Angela Saviano ◽  
Mattia Brigida ◽  
Luisa Saviano ◽  
Alessio Migneco ◽  
...  
Keyword(s):  
Gastrointestinal Bleeding ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Medical Emergency ◽  
Management Approach ◽  
Emergency Setting ◽  
Reversal Agents ◽  
Life Threatening ◽  
Andexanet Alfa

Background : Major bleeding is a life-threatening condition and a medical emergency with high mortality risk. It is often the complication of anticoagulant’s intake. Anticoagulants are commonly used for the prevention and the treatment of thrombotic events. The standard therapy with vitamin K antagonist (warfarin) has been frequently replaced by direct oral anticoagulants (DOACs). The latter agents (rivaroxaban, apixaban, edoxaban, dabigatran, betrixaban) showed a better efficacy and safety compared to standard warfarin treatment and they are recommended for the reduction of ischemic stroke. Literature data reported a high risk of gastrointestinal bleeding with DOACs, in particular with dabigatran and rivaroxaban. In case of life-threatening gastrointestinal bleeding, these patients could benefit from the use of reversal agents. Methods: We performed an electronic search on PUBMED of the literature concerning reversal agents for DOACs and gastrointestinal bleeding in the Emergency Department from 2004 to 2020. AIM: This review summarizes the current evidences about three reversal agents idarucizumab, andexanet alfa and ciraparantag, and the use of the first two in the emergency setting in patients with an active major bleeding or who need urgent surgery to offer physicians indications for a better management approach in order to increase patient’s safety. Conclusion: Although these agents have been marketed for five years (idarucizumab) and two years (andexanet alfa) respectively, and despite guidelines considering antidotes as first-line agents in treating life-threatening hemorrhage when available, these antidotes seem to gain access very slowly in the clinical practice. Cost, logistical aspects and need for plasma level determination of DOAC for an accurate therapeutic use probably have an impact on this phenomenon.. An expert multidisciplinary bleeding team should be established so as to implement international guidelines based on local resources and organization.

scholarly journals Reversal Activity and Toxicity of Heparin-Binding Copolymer after Subcutaneous Administration of Enoxaparin in Mice

2021 ◽  
Vol 22 (20) ◽  
pp. 11149
Author(s):  
Justyna Swieton ◽  
Joanna Miklosz ◽  
Shin-Ichi Yusa ◽  
Krzysztof Szczubialka ◽  
Dariusz Pawlak ◽  
...  
Keyword(s):  
Biochemical Parameters ◽  
Histological Analysis ◽  
Anticoagulant Activity ◽  
Subcutaneous Administration ◽  
Histopathological Analysis ◽  
Heparin Binding ◽  
Adverse Side Effects ◽  
Life Threatening ◽  
Antifactor Xa ◽  
Uncontrolled Bleeding

Uncontrolled bleeding after enoxaparin (ENX) is rare but may be life-threatening. The only registered antidote for ENX, protamine sulfate (PS), has 60% efficacy and can cause severe adverse side effects. We developed a diblock copolymer, heparin-binding copolymer (HBC), that reverses intravenously administered heparins. Here, we focused on the HBC inhibitory activity against subcutaneously administered ENX in healthy mice. BALB/c mice were subcutaneously injected with ENX at the dose of 5 mg/kg. After 110 min, vehicle, HBC (6.25 and 12.5 mg/kg), or PS (5 and 10 mg/kg) were administered into the tail vein. The blood was collected after 3, 10, 60, 120, 360, and 600 min after vehicle, HBC, or PS administration. The activities of antifactors Xa and IIa and biochemical parameters were measured. The main organs were collected for histological analysis. HBC at the lower dose reversed the effect of ENX on antifactor Xa activity for 10 min after antidote administration, whereas at the higher dose, HBC reversed the effect on antifactor Xa activity throughout the course of the experiment. Both doses of HBC completely reversed the effect of ENX on antifactor IIa activity. PS did not reverse antifactor Xa activity and partially reversed antifactor IIa activity. HBC modulated biochemical parameters. Histopathological analysis showed changes in the liver, lungs, and spleen of mice treated with HBC and in the lungs and heart of mice treated with PS. HBC administered in an appropriate dose might be an efficient substitute for PS to reverse significantly increased anticoagulant activity that may be connected with major bleeding in patients receiving ENX subcutaneously.

scholarly journals ANDEXANET ALFA FOR ACUTE BLEEDING DURING TREATMENT WITH ENOXAPARIN

2021 ◽  
Vol 77 (18) ◽  
pp. 1856
Author(s):  
Thijs F. van Haaps ◽  
Alexander P. Benz ◽  
Lizhen Xu ◽  
Michiel Coppens ◽  
John W. Eikelboom ◽  
...  
Keyword(s):  
Acute Bleeding ◽  
Andexanet Alfa

Safety and Efficacy of Vitamin K Antagonists versus Rivaroxaban in Hemodialysis Patients with Atrial Fibrillation: A Multicenter Randomized Controlled Trial

2021 ◽  
pp. ASN.2020111566
Author(s):  
An S. De Vriese ◽  
Rogier Caluwé ◽  
Hans Van Der Meersch ◽  
Koen De Boeck ◽  
Dirk De Bacquer
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Cardiovascular Events ◽  
Vitamin K Antagonists ◽  
Vitamin K2 ◽  
Composite Outcome ◽  
End Point ◽  
Life Threatening ◽  
K2 Group

BackgroundIn patients with normal renal function or early stage CKD, the risk-benefit profile of direct oral anticoagulants (DOACs) is superior to that of vitamin K antagonists (VKAs). In patients on hemodialysis, the comparative efficacy and safety of DOACs versus VKAs are unknown.MethodsIn the Valkyrie study, 132 patients on hemodialysis with atrial fibrillation were randomized to a VKA with a target INR of 2–3, 10 mg rivaroxaban daily, or rivaroxaban and vitamin K2 for 18 months. Patients continued the originally assigned treatment and follow-up was extended for at least an additional 18 months. The primary efficacy end point was a composite of fatal and nonfatal cardiovascular events. Secondary efficacy end points were individual components of the composite outcome and all-cause death. Safety end points were life-threatening, major, and minor bleeding.ResultsMedian (IQR) follow-up was 1.88 (1.01–3.38) years. Premature, permanent discontinuation of anticoagulation occurred in 25% of patients. The primary end point occurred at a rate of 63.8 per 100 person-years in the VKA group, 26.2 per 100 person-years in the rivaroxaban group, and 21.4 per 100 person-years in the rivaroxaban and vitamin K2 group. The estimated competing risk–adjusted hazard ratio for the primary end point was 0.41 (95% CI, 0.25 to 0.68; P=0.0006) in the rivaroxaban group and 0.34 (95% CI, 0.19 to 0.61; P=0.0003) in the rivaroxaban and vitamin K2 group, compared with the VKA group. Death from any cause, cardiac death, and risk of stroke were not different between the treatment arms, but symptomatic limb ischemia occurred significantly less frequently with rivaroxaban than with VKA. After adjustment for competing risk of death, the hazard ratio for life-threatening and major bleeding compared with the VKA group was 0.39 (95% CI, 0.17 to 0.90; P=0.03) in the rivaroxaban group, 0.48 (95% CI, 0.22 to 1.08; P=0.08) in the rivaroxaban and vitamin K2 group and 0.44 (95% CI, 0.23 to 0.85; P=0.02) in the pooled rivaroxaban groups.ConclusionsIn patients on hemodialysis with atrial fibrillation, a reduced dose of rivaroxaban significantly decreased the composite outcome of fatal and nonfatal cardiovascular events and major bleeding complications compared with VKA.Clinical Trial registry name and registration number:Oral Anticoagulation in Hemodialysis, NCT03799822

scholarly journals Croup and COVID-19 in a child: a case report and literature review

2021 ◽  
Vol 14 (9) ◽  
pp. e244769
Author(s):  
Chee Chean Lim ◽  
Jeyasakthy Saniasiaya ◽  
Jeyanthi Kulasegarah
Keyword(s):  
Paediatric Intensive Care Unit ◽  
Rare Case ◽  
Prolonged Treatment ◽  
Third Wave ◽  
Close Monitoring ◽  
Limited Experience ◽  
Threatening Condition ◽  
Life Threatening ◽  
Severe Pathology ◽  
Inflammatory Syndrome

Croup (laryngotracheitis) is frequently encountered in the emergency department in a young child presenting with stridor. We describe a rare case of croup secondary to SARS-CoV-2 in an 18-month-old child who presented with stridor and respiratory distress and required urgent intubation. Subsequently, the child developed multisystem inflammatory syndrome in children (MIS-C). The child was monitored in paediatric intensive care unit. We would like to highlight that COVID-19 croup in children may be an indicator for MIS-C, and close monitoring is warranted as MIS-C is a life-threatening condition. Our limited experience suggests that COVID-19 croup especially if associated with MIS-C has an underlying more severe pathology and may require prolonged treatment in comparison with the typical croup or even COVID-19 croup. It is important to recognise this clinical entity during a time when most countries are in a third wave of COVID-19 pandemic.

Andexanet Alfa or Prothrombin Complex Concentrate for Factor Xa Inhibitor Reversal in Acute Major Bleeding

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Charlie J. Nederpelt ◽  
Leon Naar ◽  
Pieta Krijnen ◽  
Saskia le Cessie ◽  
Haytham M. A. Kaafarani ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Prothrombin Complex Concentrate ◽  
Factor Xa ◽  
Factor Xa Inhibitor ◽  
Andexanet Alfa

Medication Dosages During Pediatric Emergencies: A Simple and Comprehensive Guide

PEDIATRICS ◽  
1989 ◽  
Vol 84 (4) ◽  
pp. 731-735
Author(s):  
CRAIG TENDLER ◽  
SUSAN GROSSMAN ◽  
JUDITH TENENBAUM
Keyword(s):  
Critical Care ◽  
Pediatric Critical Care ◽  
Drug Dosing ◽  
Pediatric Emergencies ◽  
Medical Centers ◽  
Limited Experience ◽  
Life Threatening ◽  
Drug Doses

Drug dosing during life-threatening pediatric emergencies is a source of stress for most physicians and nurses. This can be attributed to the lack of standardized drug doses for most pediatric medications, thus requiring time-consuming calculations with small margins of error. Anxiety may be further heightened by the infrequent occurrence of pediatric emergencies, resulting in a staffs limited experience with such crises. In an effort to reduce the potential for error and anxiety during administration of these pediatric critical care drugs, a majority of the major medical centers are currently using medication tables. Many prototypes have been published in the literature, but most require calculations and are incomplete in their content.

Uncontrolled bleeding during tooth extraction from an undiagnosed arteriovenous malformation

2021 ◽  
Vol 14 (8) ◽  
pp. e236983
Author(s):  
Kumar Nilesh ◽  
Swenil Shah ◽  
Amol Gautam ◽  
Sagar Thorat
Keyword(s):  
Arteriovenous Malformations ◽  
Tooth Extraction ◽  
Severe Bleeding ◽  
Space Management ◽  
Vascular Morphogenesis ◽  
Vascular Flow ◽  
Life Threatening ◽  
Surgical Manipulation ◽  
Uncontrolled Bleeding ◽  
Adult Female Patient

Arteriovenous malformations (AVMs) are rare congenital disorders of vascular morphogenesis. These lesions are characterised by high vascular flow with risk of severe bleeding from accidental trauma or surgical manipulation. Although infrequent, potentially life-threatening and fatal oral bleeding has been reported during extraction of tooth associated with AVM. This paper presents a case of uncontrolled bleeding in an adult female patient undergoing mandibular anterior tooth extraction. The bleeding was related to undiagnosed soft tissue AVM in gingivobuccal space. Management of the case with review of previously reported similar cases is presented.

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