Institutional Experience of Using Andexanet Alfa

Khadka, Sushmita; Kasireddy, Vineela; Dhakal, Pravash

doi:10.7759/cureus.9173

Cited by 5 publications

(6 citation statements)

References 22 publications

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“…The ANNEXA‐4 trial, which trended anti‐Xa activity and assessed hemostasis after andexanet alfa administration in patients experiencing acute major bleeding within 18 h of a FXa‐I, demonstrated a decrease in anti‐FXa activity up to 4 h postinfusion with good or excellent hemostasis in 82% of patients 6 . Subsequent smaller, nonrandomized studies specifically addressing intracranial or gastrointestinal hemorrhages demonstrated that 48% to 90% of patients receiving FXa‐I therapy achieved excellent or good hemostasis following andexanet alfa administration 7–13 . However, patients requiring invasive or surgical procedures have not been represented in these data.…”

Section: Introductionmentioning

confidence: 99%

“… 6 Subsequent smaller, nonrandomized studies specifically addressing intracranial or gastrointestinal hemorrhages demonstrated that 48% to 90% of patients receiving FXa‐I therapy achieved excellent or good hemostasis following andexanet alfa administration. 7 , 8 , 9 , 10 , 11 , 12 , 13 However, patients requiring invasive or surgical procedures have not been represented in these data. Furthermore, patients suspected to undergo surgical procedures within 12 h of admission were excluded from ANNEXA‐4.…”

Section: Introductionmentioning

confidence: 99%

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Reversal of apixaban and rivaroxaban with andexanet alfa prior to invasive or surgical procedures

et al. 2022

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Background: Outcomes following andexanet alfa reversal of factor Xa inhibitors in patients requiring urgent or emergent invasive procedures are lacking. This study aimed to describe efficacy and safety outcomes following andexanet alfa administration within 24 h of an invasive procedure.Methods: This single-center, observational, retrospective study included patients who received andexanet alfa within 24 h of an invasive or surgical procedure. The primary outcome was hemostatic efficacy graded as excellent, good, or poor using similar definitions to the ANNEXA-4 criteria. Secondary outcomes included hospital discharge disposition, intensive care unit (ICU) and hospital length of stay, 30-day mortality, 30-day thromboischemic event rates, and serum coagulation assay changes pre-and postreversal.Results: Forty-four patients met inclusion criteria; of these, 27 (62.8%) received apixaban and 16 (37.2%) were treated with rivaroxaban prior to admission. The indications for reversal were categorized as intracranial (n = 20 [45.5%]) or extracranial (n = 24 [54.5%]) sites. Majority of patients required emergent operative procedures (18 [40.9%]), followed by invasive device placement (10 [22.7%]) or arterial embolization (9 [20.5%]). Thirty-eight (86.4%) patients were able to be adequately graded for hemostatic efficacy. Overall, 30 (78.9%) patients achieved excellent or good hemostasis within 24 h after periprocedural administration of andexanet alfa ( 19[82.6%] apixaban vs. 11 [78.6%] rivaroxaban; 12 [80.0%] intracranial events vs. 18 [78.3%] extracranial events). Discharge disposition was most often to a short-or long-term care facilities (27 [61.4%]). Thirty-day mortality and thromboischemic complications occurred in 15 (34.1%) and 12 (27.3%) patients, respectively. Prothrombin time and | 781 BRADSHAW et al.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Reversal of apixaban and rivaroxaban with andexanet alfa prior to invasive or surgical procedures

et al. 2022

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“…Thus far, real-world experiences in both intracranial and extracranial hemorrhages have been mixed, [25][26][27][28]30,31 while a large multicenter observational study showed similar rates of inadequate hemostasis in patients with FXa inhibitor-associated hemorrhage receiving PCC 13 as those described in ANNEXA-4. However, compared to patients with extracranial hemorrhage, patients with ICH raise unique concerns given a distinct set of risk factors for further hematoma growth, 32,33 along with the relatively unpredictable nature of its occurrence.…”

Section: Discussionmentioning

confidence: 98%

Modeling the Clinical Implications of Andexanet Alfa in Factor Xa Inhibitor–Associated Intracerebral Hemorrhage

et al. 2021

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Background and Objectives:Andexanet alfa was recently approved as a reversal agent for the Factor Xa inhibitors (FXai) apixaban and rivaroxaban, but its impact on long-term outcomes in FXai-associated intracerebral hemorrhage (ICH) is unknown. We aimed to explore potential clinical implications of andexanet alfa in FXai-associated ICH in this simulation study.Methods:We simulated potential downstream implications of andexanet alfa across a range of possible hemostatic effects using data from a single center that treats FXai-associated ICH with prothrombin complex concentrate (PCC). We determined baseline probabilities of inadequate hemostasis across FXai and non-FXai patients via multivariable regression models, then determined probabilities of unfavorable 3-month outcome (modified Rankin Scale 4-6) using models comprising established predictors and each patient’s calculated probability of inadequate hemostasis. We applied bootstrapping with model parameters from this derivation cohort to simulate a range of hemostatic improvements and corresponding outcomes, then calculated absolute risk reduction (relative to PCC) and projected number needed to treat (NNT) to prevent one unfavorable outcome.Results:Training models using real-world patients (n=603 total; 55 FXai) had good accuracy in predicting inadequate hemostasis (AUC 0.78) and unfavorable outcome (AUC 0.78). Inadequate hemostasis was strongly associated with unfavorable outcome (OR 4.5, 95% CI 2.0-9.9) and occurred in 11.4% of FXai patients. Across simulated FXai patients comparable to those in the ANNEXA-4 study, predicted absolute risk reduction of unfavorable outcome was 4.9% (95% CI 1.3%-7.8%) when the probability of inadequate hemostasis was reduced by 33%, and 7.4% (95% CI 2.0%-11.9%) at 50% reduction, translating to projected NNTs of 21 (cumulative cost $519,750) and 14 ($346,500), respectively.Discussion:Even optimistic simulated hemostatic effects suggest that the costs and potential benefits of andexanet alfa should be carefully considered. Placebo-controlled randomized trials are needed before its use can definitively be recommended.

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“…The frequency of AnAl-induced heparin resistance, diagnostic methods, and appropriate treatment remain unknown. However, reports have indicated the risk of intraoperative blood clots associated with AnAlinduced heparin resistance during emergency cardiovascular surgery [1,[5][6][7][8][9][10]. Therefore, in cases where AnAl has already been administered prior to systemic heparinization, a management protocol for AnAlinduced heparin resistance must be established.…”

Section: Discussionmentioning

confidence: 99%

“…However, concerns exist among anesthesiologists regarding AnAl-induced heparin resistance [4]. Additionally, AnAl-induced heparin resistance has solely been documented in case reports, and as of present, the precise incidence as well as the optimal diagnostic and treatment approaches remain undetermined [1,[5][6][7][8][9][10]. We present a case of AnAlinduced heparin resistance managed with antithrombin during emergent aortic surgery.…”

Section: Introductionmentioning

confidence: 99%

A Case of Andexanet Alfa Induced Heparin Resistance in Emergent Aortic Surgery: Successful Anticoagulation Management Using Antithrombin Administration

Takagi,

Fukuda,

Saku

et al. 2023

Cureus

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Andexanet alfa (AnAl) is utilized for the urgent reversal of direct oral anticoagulants (DOACs) in cases of severe bleeding. While the guidelines from the Society of Thoracic Surgeons recommend AnAl for urgent cardiac surgery in patients treated with DOACs, concerns persist regarding the potential of AnAl to induce heparin resistance. This report details the case of an 85-year-old woman diagnosed with acute type A aortic dissection, who received AnAl due to prior edoxaban use. During the emergent aortic surgery, she exhibited heparin resistance following the administration of unfractionated heparin (UFH). The administration of antithrombin III (ATIII) significantly influenced activated clotting times, facilitating successful surgery while maintaining adequate anticoagulation. This case underscores the importance of cautious management of AnAl-induced heparin resistance during critical surgeries, emphasizing the role of ATIII supplementation for effective anticoagulation.

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Institutional Experience of Using Andexanet Alfa

Cited by 5 publications

References 22 publications

Reversal of apixaban and rivaroxaban with andexanet alfa prior to invasive or surgical procedures

Reversal of apixaban and rivaroxaban with andexanet alfa prior to invasive or surgical procedures

Modeling the Clinical Implications of Andexanet Alfa in Factor Xa Inhibitor–Associated Intracerebral Hemorrhage

A Case of Andexanet Alfa Induced Heparin Resistance in Emergent Aortic Surgery: Successful Anticoagulation Management Using Antithrombin Administration

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