AndexXa (coagulation factor Xa (recombinant), inactivated -zhzo) / Daiichi Sankyo, AstraZeneca - LARVOL DELTA

Machine Learning–Based risk stratification in patients with direct anti‑xa Inhibitors–Related bleeding treated with four‑factor prothrombinex complex concentrate (4F-PCC) (ASH 2025) - "Although Andexanet alfa is FDA-approvedfor reversal, its high cost and limited availability restrict its use in many centers... 4F-PCC showed efficacy and safety in the reversal of direct anti-Xa inhibitor related majorbleeding. Machine learning approach successfully identified predictors to classify patients with high andlow risk for mortality outcomes. Further large-scale prospective studies are warranted to validate this riskstratification model and support therapeutic decision-making in patients presenting with major bleeding."

Clinical • Machine learning • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders

Specific reversal agents for direct oral anticoagulants in neurosurgical emergencies - a systematic review. (PubMed, Res Pract Thromb Haemost) - "Idarucizumab and andexanet alfa are approved reversal agents, yet their effectiveness and safety in neurosurgical emergencies remain unclear. The use of DOAC reversal agents in emergency neurosurgery appears feasible and may support surgical hemostasis in selected patients. However, further research is warranted, particularly regarding the off-label use of andexanet, given the limited evidence and potential safety concerns."

Journal • Review • Cardiovascular

A UK-wide analysis of 2265 patients receiving a reversal agent for direct oral anticoagulant-associated bleeding. (PubMed, J Thromb Haemost) - "Reversal agents were generally used in patients with clinical evidence of major bleeding but were administered long after the last anticoagulant dose. In gastrointestinal bleeding, andexanet alfa was associated with a higher thrombotic risk than PCC."

Journal • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Gastroenterology • Hematological Disorders • Thrombosis

Automated Imaging and Analysis of Platelet, Coagulation and Fibrinolysis Activities Using a Novel Flow Chip-Based System at Physiological Temperature. (PubMed, Micromachines (Basel)) - "In platelet-sensitive mode, MC-2S demonstrated high sensitivity to antiplatelet therapy with aspirin or cangrelor. In coagulation-sensitive mode, it detected the anticoagulant effect of rivaroxaban plus its reversal by andexanet-α. In fibrinolysis-sensitive mode, it monitored tissue-type plasminogen activator-induced thrombus dissolution, inhibited by tranexamic acid. Collectively, the MC-2S platform was found to provide a versatile, physiologically relevant tool for functional hemostasis testing, with high potential for the acute and subacute evaluation of patient blood samples in the context of bleeding disorders, thrombosis risk, and drug monitoring."

Journal • Cardiovascular • Hematological Disorders • Thrombosis

Characteristics of Intracranial Hemorrhage in Patients on Factor-Xa Inhibitors: Japan Stroke Data Bank. (PubMed, Intern Med) - "Results A total of 859 patients (rivaroxaban, n=227; apixaban, n=355; edoxaban, n=277) with ICH (ICH: n=822, age 79±9 years, 38.6% female; SAH: n=37, age 79±10, 75.7% female) were investigated. Conclusion This study presents the clinical outcomes prior to the approval of andexanet alfa. Further studies are needed to evaluate post-approval outcome changes."

Journal • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Subarachnoid Hemorrhage

Andexanet Alfa in Emergency Cranial Neurosurgical Procedures: A Bicentric Analysis of Efficacy and Safety. (PubMed, Neurocrit Care) - "Our findings suggest that andexanet alfa is highly effective in preventing secondary bleeding during neurosurgery in patients on factor Xa inhibitors. However, the risk for ischemic events must be carefully considered."

Journal • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Gastrointestinal Disorder • Hematological Disorders • Pulmonary Embolism • Respiratory Diseases

Clinical laboratory testing of blood from patients presenting to the emergency department with acute bleeding due to factor Xa inhibitors: An unmet medical need. (PubMed, Clin Chim Acta) - "For patients on warfarin, stat testing of blood for the prothrombin time and calculation of the International Ratio (PT-INR) are used to determine if acute bleeding is caused by excess anticoagulation. Direct acting oral anticoagulants (DOACs) include those that inhibit Factor Xa (apixaban, rivaroxaban, edoxaban, and betrixaban) or Factor IIa (dabagatran)...However, current laboratory assays for anti-Factor Xa are calibrated for the specific DOAC used and results are not typically available in emergency departments. Therefore, there is a need to produce a rapid bedside blood test that can detect bleeding to any DOAC drug that was prescribed."

Journal • Cardiovascular • Ischemic stroke

Emergency Reversal of Antithrombotics in Intracerebral Hemorrhage: An Update. (PubMed, Curr Neurol Neurosci Rep) - "Current data suggests reversal of vitamin K antagonists with intravenous vitamin K and 4-factor prothrombin complex concentrates (4f-PCC), reversal of dabigatran with idarucizumab, and reversal or direct oral factor Xa inhibitors with either 4f-PCC or andexanet-alfa. While platelet transfusion is not suggested for antiplatelet-associated ICH, DDAVP may be reasonable, and a new reversal agent is under development for ticagrelor. Rapid reversal of antithrombotic-associated coagulopathy in the context of ICH may prevent ICH expansion and improve neurological outcomes."

Journal • Review • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders

Ondexxya for Intravenous Injection 200mg Drug Use Result Investigation (All Case Investigation) (clinicaltrials.gov) - P=N/A | N=300 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Nov 2025 ➔ Aug 2026 | Trial primary completion date: Nov 2025 ➔ Aug 2026

Trial completion date • Trial primary completion date

Predictors of hematoma expansion in intracerebral hemorrhage associated with factor Xa inhibitors. (PubMed, Front Neurol) - "Andexanet alfa, a specific reversal agent for factor Xa inhibitors, has the potential to mitigate hematoma expansion (HE)...In univariate analysis, significant predictors of HE were an irregular margin and/or heterogeneity of the hematoma on computed tomography (CT) (p = 0.009), an initial CT performed within 4 h after drug intake (p = 0.034), and edoxaban use (p = 0.041)...The predictors of HE were an irregular margin or heterogeneous hematoma, and an initial CT performed within 4 h after drug intake. Reversal decisions based on hematoma volume, or interval from onset to initial CT may be inappropriate."

Journal • Cerebral Hemorrhage • Hematological Disorders

Andexanet Should Be Used to Reverse Xai Anticoagulants (ASH 2023) - No abstract available

Debate: PCC or Andexanet alfa for Managing Bleeding in Patients on Oral Xa Inhibitors? (ASH 2023) - "The participants in this debate will take the opposite sides of the question: should most patients with FXa-inhibitor-associated bleeding receive andexanet alpha (over prothrombin complex concentrates and/or best supportive care)? The session will include a detailed examination of the risks and the benefits of different managements strategies that may be considered for patients who are in this potentially precarious clinical situation."

Clinical

Comparing Hemostatic Efficacy of Andexanet Alfa and 4-Factor Prothrombin Complex Concentrate in a Polytrauma Porcine Model Treated with Apixaban (ASH 2024) - "Post-mortem histopathology revealed no thromboembolic complications in any treatment group.Conclusions : This study demonstrated that both high-dose 4F-PCC and andexanet alfa are effective in achieving survival, hemostatic control, and reduction in bleeding following polytrauma in a porcine model of apixaban anticoagulation. Although hemostasis was achieved more rapidly with andexanet alfa, which directly reduced the levels of anti-FXa inhibitor levels, treatment with 4F-PCC showed sustained restoration of factors II, IX, and X levels, as well as thrombin generation after polytrauma."

Preclinical • Cardiovascular • Liver Failure • Musculoskeletal Diseases • Orthopedics

Rapido: Results from a UK-Wide Audit of 2477 Patients Who Received a Reversal Agent for a Direct Oral Anticoagulant (ASH 2024) - "Although a specific reversal agent for dabigatran, idarucizumab, was approved for use in the UK in 2016, the predominant option for patients taking apixaban, edoxaban, and rivaroxaban has until recently been off-licence prothrombin complex concentrate (PCC). Importantly, the data highlight delays in identification and treatment of bleeds. Further, detailed analysis of this rich dataset is on-going, and a propensity score-matched analysis of patients with GI hemorrhage will be performed to compare outcomes in patients treated with andexanet alfa, Beriplex and Octaplex."

Clinical • Atrial Fibrillation • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Venous Thromboembolism

An Evaluation of Andexanet Alfa v. Standard of Care for Reversal of Doac-Induced Intracranial Hemorrhage – a Systematic Review and Meta-Analysis (ASH 2024) - "Eighteen (81.8%) studies predominately or exclusively used 4-factor prothrombin complex concentrate (4F-PCC) as the standard of care, 4 (18.2%) studies used 3-factor and activated PCC, one examined fresh frozen plasma (FFP), and one examined tranexamic acid. The two most commonly documented DOACs were apixaban (n = 1072) and rivaroxaban (n = 716)...Conclusions Our meta-analysis found improved hemostatic efficacy with Andexanet alfa compared to standard-of-care, with no effect on thrombotic complications and mortality rates. This suggests that Andexanet alfa is a favourable treatment option for hemostasis in patients experiencing life-threatening ICH."

Retrospective data • Review • Atrial Fibrillation • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Venous Thromboembolism

Andexanet alfa vs standard of care for factor Xa inhibitor-induced intracranial hemorrhage-a systematic review and meta-analysis. (PubMed, Res Pract Thromb Haemost) - "Our meta-analysis found low-certainty evidence supporting improved hemostatic efficacy with andexanet alfa compared with standard of care, with a decrease in mortality and no effect on thrombotic complications. Further randomized data is required to establish a conclusive clinical benefit favoring andexanet alfa."

Journal • Retrospective data • Review • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Thrombosis

In vitro anticoagulant effect of nafamostat mesylate in andexanet-induced heparin resistance. (PubMed, Thromb Res) - No abstract available

Journal • Preclinical

INITIAL EXPERIENCE WITH THE USE OF ANDEXANET ALFA ON INTRACRANIAL HEMORRHAGE (WSC 2025) - "There were 4 patients (31%) receiving edoxaban, 4 (31%) receiving rivaroxaban, and 5 (38%) receiving apixaban. Andexanet alfa was effective on FXa inhibitor–related ICH. It seems to be an favorable therapeutic agent for patients receiving FXa inhibitors whether they undergo surgery or conservative treatment."

Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Subarachnoid Hemorrhage

Andexanet alfa-induced heparin resistance during percutaneous coronary intervention for ST-elevation myocardial infarction: a case report. (PubMed, Eur Heart J Case Rep) - "Andexanet alfa is a recombinant modified factor Xa decoy protein used to reverse the anticoagulant effects of direct oral factor Xa inhibitors, including apixaban, rivaroxaban, and edoxaban. Although STEMI following andexanet alfa administration has been reported, this case underscores the additional challenge of profound heparin resistance compromising timely anticoagulation during emergent PCI. Rapid recognition of andexanet alfa-induced heparin resistance is crucial in urgent PCI settings to ensure effective anticoagulation and prevent procedural delays that may compromise outcomes."

Journal • Cardiovascular • Infectious Disease • Musculoskeletal Diseases • Myocardial Infarction • Orthopedics • Pneumonia • Respiratory Diseases

Andexanet alfa for the reversal of the low-molecular-weight heparin enoxaparin. (PubMed, Res Pract Thromb Haemost) - "In enoxaparin-treated subjects, andexanet reduced anti-Xa activity and achieved effective hemostasis in 88% of patients. Results align with findings of patients using apixaban, rivaroxaban, or edoxaban."

Journal • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Venous Thromboembolism

Volume and Location Analysis of Intracerebral Hemorrhage for the Appropriate Use of Andexanet Alfa. (PubMed, Neurol Med Chir (Tokyo)) - "Andexanet alfa prevented hematoma expansion in these regions of small hematomas (p = 0.0285). In conclusion, small hematomas located in deep regions such as the thalamus or brainstem and bigger than those in any location should be considered for treatment with andexanet alfa as a reversal agent of Factor Xa inhibitors."

Journal • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders

Risk Factors Associated with Thrombus Development Following Pharmacologic Anticoagulation Reversal with Coagulation Factor Xa [Recombinant], Inactivated-zhzo. (PubMed, Hosp Pharm) - "Andexanet alfa (AA), a recombinant coagulation factor Xa, is approved as an antidote for the treatment of bleeding secondary to rivaroxaban and apixaban. A strong association existed between major surgery within 30 days and thrombotic complications following AA administration. Larger studies are needed to validate these findings and refine risk stratification post-AA administration."

Journal • Cardiovascular • Hematological Disorders • Thrombosis

Procoagulant off-target effect of the direct oral anticoagulant reversal agent Andexanet alfa. (PubMed, Blood Vessel Thromb Hemost) - "Treatment of control plasmas with rivaroxaban, apixaban, or edoxaban resulted in an impaired thrombin generation, exemplified by a prolonged lag time and reduced thrombin peak height. The action mechanism involves TFPI inhibition and neutralization of antithrombin-heparin complexes. This may account for the incidence of thrombosis observed in patients treated with Andexanet alfa."

Journal • Cardiovascular • Hematological Disorders • Thrombosis

Latin America Multidisciplinary Consensus Panel on Management of Severe Bleeding in the Anticoagulated Patient. (PubMed, J Emerg Med) - "This review highlights the significance of appropriate risk stratification and management strategies for bleeding complications associated with anticoagulants. The manuscript emphasizes the need for adaptable management strategies in regions like Latin America, where resource limitations may impact the availability of specific reversal agents."

Journal • Hematological Disorders

Bleeding Risks and Urgent Orthopedic Surgery: Navigating Infection, Anticoagulation, and Hemodynamic Instability in a Congenital Cardiac Patient (ASA 2025) - "Despite recent aspirin and rivaroxaban use, orthopedic surgery felt urgent necessity for hardware removal. Given Andexanet alfa unavailability, hematology and cardiac surgery prioritized bleeding risk and planned reversal with 4FPCC at 25 units/kg prior to incision.In the OR, purulent fluid was found around the hardware. She developed hypotension with blood loss. She was given transfusions and underwent successful wound-washout, transferred to PICU, and discharged post-op day 5 with aspirin."

Clinical • Surgery • Cardiovascular • Hematological Disorders • Hypotension • Infectious Disease • Orthopedics