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

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

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

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

The use of andexanet alfa for life-threatening hemorrhagic shock in a DOAC-treated patient due to atraumatic splenic rupture and unexpected diagnosis of visceral leishmaniasis. (PubMed, Minerva Anestesiol) - No abstract available

Journal • Hematological Disorders • Infectious Disease

Conservative management of patient with massive rivaroxaban overdose in normal renal function without bleeding. (EUSEM 2025) - "Haemodynamic parameters was stable.The physical examination and the electrocardiogram showed no abnormalities.The laboratory results showed PT of 22.2%,INR 2.22,APTT 56.6 sec,fibrinogen 2.63g/L,TT of 19.7sec.The blood count was normal as well as electrolytes,liver,and kidney function.Rivaroxaban activity was 1268ng/mL.In emergency department the patient was closely monitored and treated with intravenous electrolyte solution and activated charcoal.After that she was referred to the Clinical Toxicology Department.Conservative treatment was continued and on the next day clinical condition improved.Rivaroxaban concentration decreased from initial point of 1268ng/mL to <20 ng/mL.The patient was discharged from the hospital in 2 days.The major concern of rivaroxabane overdose is bleeding, and supportive measures is the standard of care since the specific antidote andexanet alfa is absent.The maximum anticoagulant effect of rivaroxaban is 2–4 h, and its half-life is 5–9 h,..."

Clinical

Time to hemostatic agent administration increases mortality in veterans with factor Xa inhibitor-related intracranial hemorrhage. (PubMed, Am J Emerg Med) - "In Veterans with fXa inhibitor-related ICH receiving AA or 4F-PCC, there was no difference between AA and 4F-PCC in time to hemostatic treatment. Time to hemostatic agent administration increased odds of 90-mortality by 0.4 % for every minute, but did not differ depending on the hemostatic agent used."

Journal • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders

Evaluating the Role of Andexanet Alfa in Managing Intracranial Hemorrhage in Patients on Vascular-Dose Rivaroxaban: A Clinical Dilemma. (PubMed, Cardiovasc Drugs Ther) - No abstract available

Journal • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders

Reversing Anticoagulants: Influence of Anticoagulation Stewardship and Key Considerations for Optimizing Outcomes. (PubMed, Ann Pharmacother) - "Recent advances in anticoagulation stewardship have created opportunities to standardize and optimize the reversal of anticoagulants, especially in urgent life-threatening bleeding events. This article explores how pharmacists provided anticoagulation stewardship activities positively impact outcomes related to urgent anticoagulation reversal."

Journal

Efficacy of andexanet alfa in non-surgical patients with spontaneous DOAC related intracerebral hemorrhage. (PubMed, Clin Neurol Neurosurg) - "In our study, patients who received Andexxa therapy and non-surgical management of spontaneous ICH showed no difference in ICH expansion within 24 h but had increased cost of care. Further studies should examine whether Andexxa is of clinical value for patients with spontaneous ICH."

Journal • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders

Prothrombin Complex Concentrate in Direct Oral Anticoagulant Reversal: A Systematic Scoping Review. (PubMed, J Emerg Med) - "Further high-quality studies are essential to deepen understanding regarding PCC effectiveness and safety in achieving clinical hemostasis. However, this review provides the information regarding PCC as an option when DOAC-specific reversal agents are unavailable, or the type of DOAC is unknown."

Journal • Atrial Fibrillation • Cardiovascular • Hematological Disorders • Venous Thromboembolism

Andexanet alfa increases 30-day thrombotic events relative to four-factor prothrombin complex concentrate for factor Xa inhibitors-related intracerebral hemorrhage in veterans. (PubMed, Am J Emerg Med) - "In Veterans with fXa inhibitor-related ICH receiving AA or 4F-PCC, there was no difference in 90-day mortality. Consistent with previous literature from non-Veterans studies, 30-day thrombotic events were significantly higher in Veterans who received AA, including a significant increase in AIS. This study adds to the growing body of literature demonstrating higher thrombotic risks with AA. Selection of AA should be carefully weighed against the risk of thrombotic events."

Journal • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Ischemic stroke • Myocardial Infarction • Respiratory Diseases • Venous Thromboembolism

Major publications in the critical care pharmacotherapy literature: 2024. (PubMed, J Crit Care) - "This review identified, summarized, and evaluated high impact studies relevant to critical care pharmacotherapy published in 2024."

Journal • Review • Cerebral Hemorrhage • CNS Disorders • Critical care • Hematological Disorders • Infectious Disease • Pneumonia • Respiratory Diseases • Septic Shock • Stress Ulcer

Management of emergencies in direct oral anticoagulant-treated patients: practice pearls (PubMed, Orv Hetil) - No abstract available

Journal • Review

Pharmacovigilance insights into drug-associated venous thromboembolism. (PubMed, Int J Surg) - "A total of 135 medications showed positive signals for VTE (58 unmentioned in package inserts). The high-risk profile of anti-tumor agents and immunomodulators was highlighted. These findings provide robust data-driven guidance for clinical pharmacotherapy to mitigate VTE risks."

Adverse events • Journal • Cardiovascular • Oncology • Venous Thromboembolism

Retrospective Study on Characteristics and Outcomes in Hospitalised Patients Treated With Ondexxya (clinicaltrials.gov) - P=N/A | N=100 | Recruiting | Sponsor: AstraZeneca | Trial completion date: May 2025 ➔ Aug 2025 | Trial primary completion date: May 2025 ➔ Aug 2025

HEOR • Real-world evidence • Trial completion date • Trial primary completion date • Hematological Disorders

Perioperative on-demand reversal with andexanet alfa: monitoring reversal and timing of re-anticoagulation. (PubMed, Br J Anaesth) - No abstract available

Journal

TFPIa activity suppression by Andexanet alfa is partially restored by protein S and factor V-short (ISTH 2025) - "Results AA efficiently reversed rivaroxaban in plasma. Similarly, AA-bound TFPIα was unable to inhibit FIXa generation in the absence of cofactors. However, when PS and FV-short were added, AA-TFPIα inhibited FIXa generation with 58% and 86% inhibition observed at 0.25nM and 1nM AA-TFPIα, respectively, compared to 95% inhibition by FXa-bound TFPIα."

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