scholarly journals 769: COMPARISON OF 4F-PCC AND ANDEXANET ALFA FOR REVERSAL OF APIXABAN- AND RIVAROXABAN-ASSOCIATED ICH

2021 ◽  
Vol 50 (1) ◽  
pp. 378-378
Author(s):  
Michelle Lipski ◽  
Stacy Pasciolla ◽  
Kevin Wojcik ◽  
Brian Jankowitz ◽  
Lauren Igneri
Keyword(s):  
Andexanet Alfa

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 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

scholarly journals Safety, pharmacokinetics, and reversal of apixaban anticoagulation with andexanet alfa

2017 ◽  
Vol 1 (21) ◽  
pp. 1827-1838 ◽  
Author(s):  
Deborah Siegal ◽  
Genmin Lu ◽  
Janet M. Leeds ◽  
Mark Karbarz ◽  
Janice Castillo ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Healthy Subjects ◽  
Preclinical Models ◽  
Key Points ◽  
Andexanet Alfa

Key Points Andexanet reversed apixaban anticoagulation in healthy volunteers within minutes after administration and for the duration of infusion. Andexanet was generally well tolerated, with no evidence of prothrombotic activity in preclinical models and in healthy subjects.

scholarly journals Is It Truly “Alpha”? Incidence of Thrombotic Events With Andexanet Alfa at a Single Academic Medical Center

2020 ◽  
Vol 75 (5) ◽  
pp. 675-676 ◽  
Author(s):  
Katie A. Parsels ◽  
Robert W. Seabury ◽  
William Darko ◽  
Luke A. Probst ◽  
Gregory M. Cwikla ◽  
...  
Keyword(s):  
Medical Center ◽  
Academic Medical Center ◽  
Academic Medical ◽  
Andexanet Alfa

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

Abstract 212: Andexanet Alfa, a Universal Antidote for Reversal of Anticoagulation of Factor Xa Inhibitors in Healthy Human Volunteers

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Mark Crowther ◽  
Alexander M Gold ◽  
Genmin Lu ◽  
Janet M Leeds ◽  
Brian L Wiens ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Statistical Significance ◽  
Factor Xa ◽  
Clinical Results ◽  
Phase 2 ◽  
Healthy Human ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Secondary Endpoints ◽  
Andexanet Alfa

Introduction: Andexanet alfa (AnXa) is a recombinant modified fXa molecule that acts as a specific antidote for fXa inhibitors. We report clinical results in healthy subjects anticoagulated with apixaban (apix), rivaroxaban (riva), edoxaban (edox), or enoxaparin (enox), demonstrating rapid and sustained reversal of anticoagulation following administration of AnXa. Methods: These were Phase 2/3 randomized, double-blind, placebo-controlled studies in healthy subjects. In Phase 2, about153 subjects age18 - 45 were given one of the fXa inhibitors (apix 5 mg BID, riva 20 mg QD, edox 60 mg QD or enox 40 mg QD) for 6 days. AnXa or placebo (3:1 randomization) was given IV on Day 6, 3hrs after the last inhibitor dose (∼inhibitor Cmax). Safety was followed through Day 48. A range of AnXa doses (bolus or bolus+infusion) was evaluated by correction of biomarkers (anti-fXa activity, free inhibitor concentrations and thrombin generation (TG)). In Phase 3 (ANNEXA™), older subjects age 50 to 75 were dosed with apix (5 mg BID) or riva (20 mg QD) for 4 days. ANNEXA™-A had 63 subjects treated with apix. AnXa (400 mg bolus; 400 mg bolus plus 4 mg/min x 2hr infusion) or placebo (3:1 randomization) was given on Day 4, 3 hrs after the last apix dose. ANNEXA™-R had 82 subjects treated with riva. AnXa (800 mg bolus; 800 mg bolus plus 8 mg/min x 2hr infusion) or placebo (2:1) was given on Day 4, 4 hrs after the last riva dose. Safety was followed through Day 43. Results: About 298 healthy subjects were enrolled in the studies. AnXa demonstrated rapid and sustained reversal of both direct and indirect fXa inhibitors as measured by correction of biomarkers. The ANNEXA™ studies confirmed findings from Phase 2, and met all primary (reversal of anti-fXa) and secondary endpoints (reduction of free inhibitor concentration and restoration of TG) with high statistical significance. AnXa was well-tolerated with no serious adverse events, thrombotic events, or antibodies to fX or fXa reported. Conclusion: AnXa treatment results in rapid and sustained reversal of anticoagulation of fXa inhibitors. A Phase 3b/4 confirmatory study (ANNEXA-4) in patients with acute major bleeds is ongoing.

Abstract TP352: Safety and Efficacy of Andexanet Alfa in Patients With Life Threatening Intracerebral Hemorrhage: A Single Center Experience

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Syed Daniyal Asad ◽  
Stephanie R Lombardi ◽  
Ilene Staff ◽  
Amre M Nouh ◽  
Mark J Alberts
Keyword(s):  
Intracerebral Hemorrhage ◽  
Factor Xa ◽  
Hospital Length ◽  
Factor Xa Inhibitors ◽  
Hematoma Expansion ◽  
Amyloid Angiopathy ◽  
Single Center ◽  
Discharge Disposition ◽  
Ischemic Complications ◽  
Andexanet Alfa

Background: Intracerebral hemorrhage (ICH) is a devastating condition with high 30- day mortality. Up to a third of patients experience hematoma expansion within the first 24 hours; anticoagulation with factor Xa inhibitors may increase the risk of expansion and poor outcomes. Objective: We assessed our experience using Andexanet alfa (Aα) by evaluating stabilization of the hematoma and ischemic complications. Methods: We conducted a single center prospective observational study on all patients receiving Aα for reversal of anticoagulation in the setting of an ICH and use of Factor Xa inhibitors. The degree of hematoma expansion within 12 hours of drug administration on non-contrast head CT was categorized as 'excellent' (<20% increase in hematoma size), ‘good' ( > 20-<35%), and 'poor' ( > 35%). Secondary outcomes included dosage, median length of stay, mortality, modified Rankin score (mRS), discharge disposition, and ischemic complications. Results: Fifteen patients received Aα (5=lobar, 5=deep, 5= multicompartment). One patient with a presumed deep hemorrhage was excluded because subsequent imaging showed chronic mineralization. The predominant etiologies were hypertension (40%), amyloid angiopathy (26.6%) and trauma (13.3%). The median age was 86 years (IQR 19) and median ICH score on arrival was 2 (IQR 2), and median hematoma size was 14.3 mL (IQR 34.5). Most patients (71.4%) received the low dose formulation. Based on hematoma expansion, 64.3%, 14.3% and 21.4% of patients achieved excellent, good and poor hemostasis, respectively. Reduction in hematoma size was seen in 20% (n=3) while 13.3% (n=2) patients had no expansion. Median ICU and hospital length of stays were 2.0 days (IQR 2.2) and 6.6 days (IQR 9.78) respectively. Mortality was 28.6% and median mRS upon discharge was 4 (IQR 2), with most patients discharged to rehabilitation facilities (60%). There were no ischemic complications. Conclusion: Our experience is consistent with the results of the ANNEXA 4 study with 78.6% of patients showing excellent or good hemostasis. These results led to improved clinical outcomes, with 60% of patients being discharged to rehabilitation. These data support the efficacy of this treatment paradigm in a real-world setting.

Sign in / Sign up

Export Citation Format

Share Document