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

Disseminated Intravascular Coagulation Following Idarucizumab and Andexanet Alfa: Assessment of a Signal of Disproportionate Reporting From the Food and Drugs Administration Adverse Event Reporting System (FAERS) Database. (PubMed, Drug Saf) - "The disproportionality analysis of the FAERS allowed us to highlight the associations between idarucizumab-DIC and andexanet-alfa-DIC, which might otherwise have remained unobserved due to the rarity of DIC and the low utilization of idarucizumab and andexanet alfa. Although the case-by-case evaluation was limited by the intrinsic indication bias, a causal link remained possible in those cases that occurred soon after administration. Since DIC is a life-threatening and often fatal condition, further investigation is warranted while close follow-up of high-risk patients may be considered to promptly detect any sign of coagulopathy following the administration of DOAC reversal agents. Any such observed adverse events should be reported to the relevant pharmacovigilance system in a timely manner."

Adverse events • Journal • Cardiovascular • Hematological Disorders

Andexanet Alfa Versus Prothrombin Complex Concentrate in the Perioperative Setting (SCCM 2026) - "Subjective worsening of bleeding and the incidence of any thrombotic event within 24 hours were also assessed. The study included 16 patients on apixaban (mean age 74.6 years), with 11 receiving 4F-PCC and 5 receiving andexanet alfa. This study suggests a clinical trade-off between reversal agents. 4F-PCC achieved efficacy per the secondary endpoint but was associated with additional procoagulant use and the sole VTE occurrence. Andexanet alfa required no additional procoagulant therapy and had a preferable safety profile, though sample sizes were small in both cohorts."

Cerebral Hemorrhage • CNS Disorders • Hematological Disorders

Time to Anticoagulation Reversal at a Large, Academic, Regional Referral Center (SCCM 2026) - "The purpose of this study was to determine the time from anticoagulation reversal order to administration in patients with major bleeding of all types and to identify potential operational or clinical barriers that could result in delayed administration. This was a retrospective chart review at a large academic level 1 trauma center of adult patients that received anticoagulation reversal with four-factor prothrombin complex concentrate (4F-PCC), andexanet alfa (AA), or idarucizumab from January 1, 2024 to December 31, 2024...Patients were primarily female (52.1%), median age of 75, on apixaban prior to admission (72.9%), presented with ICH (41.7%), and located in the ED (57.3%)... Overall median time to anticoagulation reversal for all major bleeding types met current recommendations for time to administration in 60 minutes or less, however, median door to anticoagulation reversal for patients located in the ED did not achieve this goal."

Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Mood Disorders

Andexanet Alfa Versus 4F-PCC for Reversal of Apixaban and Rivaroxaban in Trauma Patients (SCCM 2026) - "In trauma patients requiring FXaI reversal, 4F-PCC was associated with higher rates of excellent HE in patients with intracranial bleeds. There was no significant difference in extracranial bleeds or overall safety outcomes. Further research is needed to guide optimal FXaI reversal in trauma patients."

Clinical • Atrial Fibrillation • Cardiovascular • Mood Disorders

Door-to-Treatment Time of Anticoagulant-Associated Spontaneous ICH (SCCM 2026) - "This medication use evaluation assessed time to treatment with andexanet alfa (AA) or 4-factor prothrombin complex concentrate (PCCs) in patients presenting with spontaneous ICH. Adults receiving AA or 4-factor PCCs at a comprehensive stroke center for anticoagulant associated spontaneous ICH were included...Secondary outcomes were a comparison of time to treatment with either AA or PCCs, comparison of compounding times, time to head computed tomography (CT), comparison of direct oral anticoagulant (DOAC) versus warfarin, and impact of clinical pharmacist involvement. A total of 62 patients (51 AA; 11 PCCs) were included... Time to treatment of anticoagulant associated ICH was frequently not within the 60-minute recommendation indicating the need for further initiative to improve door to treatment times. Utilizing clinical pharmacists on the interdisciplinary team might improve door to treatment times in anticoagulant associated ICH."

Cardiovascular • Cerebral Hemorrhage • Hematological Disorders

Quantifying Inappropriate Andexanet Alfa Use Prior to Institutional Policy Revision: A Review of Fifty Consecutive Administrations (THSNA 2026) - "Objective: Under the prior institutional policy, Andexxa could be ordered by ED, inpatient, or surgical attendings (or supervised trainees), with haematology consultation mandated only for selected scenarios such as subacute CNS bleeding, nonoperative trauma, urgent surgery, or reversal of non-apixaban/rivaroxaban agents. More than one-third of pre-policy Andexxa administrations were questionable, driven largely by preventable dosing and timing deviations. These findings directly shaped the revised institutional policy, which now: (1) restricts Andexxa use to explicit life-threatening criteria with detailed critical-site and hemodynamic definitions; (2) requires pharmacist review and hematology attending approval for any non-criteria case, perioperative use, >18-hour timing, or prior PCC exposure; and (3) designates 4F-PCC as the preferred strategy in several scenarios, including pericardial tamponade and non-critical-site bleeding without hemodynamic compromise. The..."

Clinical • Review • Hematological Disorders

Paradoxical Apixaban Anti-Xa Levels After Andexanet Alfa: A Case Report on Unreliable Laboratory Monitoring and Early Thrombotic Risk (THSNA 2026) - "Background: Andexanet alfa is an approved reversal agent for apixaban and rivaroxaban, but its use is complicated by thrombotic risk and significant limitations in laboratory monitoring. This case highlights the critical unreliability of standard anti-Xa assays after andexanet alfa administration, as evidenced by paradoxically elevated and clinically implausible apixaban levels. These laboratory values provide no meaningful guidance for post-reversal decision-making and should not influence timing of re-anticoagulation. Additionally, the patient experienced a thrombotic event far earlier than typically reported, underscoring the need for individualized risk–benefit assessment in high-risk patients."

Case report • Clinical • Cardiovascular • Penile Cancer • Squamous Cell Carcinoma • Venous Thromboembolism

Andexanet Alfa Versus 4F-PCC for Direct Anticoagulation Reversal in Intracranial Hemorrhage (SCCM 2026) - "In this real-world analysis, andexanet alfa was linked to a higher risk of significant intracranial hemorrhage growth than 4F-PCC, despite similar rates of neurological deterioration, thromboembolic events, functional disability, and mortality. 4F-PCC may serve as a clinically viable alternative for reversing FXa inhibitor anticoagulation in intracranial hemorrhage."

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

SPONTANEOUS RECTUS SHEATH HEMATOMA AND ACUTE LIMB ISCHEMIA IN AN ELDERLY PATIENT ON APIXABAN: A RARE INTERSECTION OF HEMORRHAGIC AND THROMBOTIC COMPLICATIONS (ACC 2026) - "Case: A 76-year-old man with CAD, PAD, and AF on apixaban and clopidogrel presented with acute abdominal pain and hypotension...IV heparin was started with relief... High-dose andexanet alfa rapidly reverses factor Xa inhibitors but carries significant thrombotic risk. Careful monitoring and individualised dosing are essential to balance hemorrhagic control against thrombosis."

Clinical • Cardiovascular • CNS Disorders • Hematological Disorders • Hypotension • Subarachnoid Hemorrhage • Thrombosis

Risk factors for drug-related ischemic stroke: an analysis of the FDA adverse event reporting system (FAERS). (PubMed, J Clin Neurosci) - "This large-scale FAERS analysis systematically characterized drug-IS associations, identifying multiple strong and independent pharmacological risk signals and revealing temporal patterns. The findings provide real-world evidence to guide clinical decision-making and targeted pharmacovigilance."

Adverse events • Journal • Cardiovascular • Ischemic stroke • Oncology

Andexanet Alfa for Life-Threatening Bleeding Following Factor Xa Inhibitor Treatment: Postmarketing Surveillance Study in Japan. (PubMed, JACC Asia) - "This study supports the safety and effectiveness of andexanet alfa in a real-world population of Japanese patients with FXaI-associated major bleeds."

Journal • P4 data • CNS Disorders

Targeted Anticoagulant Reversal, Unintended Consequences: Lessons From Andexanet Alfa. (PubMed, Eur Heart J Cardiovasc Pharmacother) - No abstract available

Journal

Dabigatran Failure Leading to Stroke: A Cautionary Tale in Anticoagulant Switching Before AF Ablation Procedures. (PubMed, Heart Lung Circ) - No abstract available

Journal • Atrial Fibrillation • Cardiovascular

Andexanet alfa Reduces Hematoma Expansion Following Controlled Cortical Impact in Mice Pretreated with Rivaroxaban. (PubMed, Neurocrit Care) - "Our experimental data suggests that the use of andexanet alfa improves functional outcomes by reduction of factor Xa inhibitor-associated hematoma expansion in the subacute phase following TBI."

Journal • Preclinical • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Vascular Neurology

D9609C00001: A trial to learn how well different doses of andexanet alfa work and how they affect blood clotting throughout the body in healthy adults who have taken an FXa inhibitor (clinicaltrialsregister.eu) - P1 | N=108 | Recruiting | Sponsor: AstraZeneca AB

New P1 trial • Thrombosis

Adrenal hemorrhage requiring apixaban reversal in the setting of active deep vein thrombosis and heparin-induced thrombocytopenia: A case report. (PubMed, Am J Health Syst Pharm) - "This case illustrates the intersection of BAH, active thrombosis, and HIT, where guideline-directed reversal strategies are limited. It underscores the challenges of selecting and timing anticoagulation reversal in patients with recent thrombotic events and contraindications to standard agents, highlighting the importance of individualized, interdisciplinary decision-making in managing complex anticoagulation scenarios."

Journal • Cardiovascular • Hematological Disorders • Infectious Disease • Mood Disorders • Orthopedics • Septic Shock • Thrombocytopenia • Thrombosis • Venous Thromboembolism

Efficacy and Safety of Direct Oral Anticoagulant Reversal Agents in Intracerebral Hemorrhage: A Systematic Review and Meta-analysis (AAN 2026) - "Objective: To evaluate the efficacy and safety of direct oral anticoagulant (DOAC) reversal agents in patients with intracerebral hemorrhage (ICH).Background: Patients on DOACs who develop ICH often receive reversal therapy with agents like 4-factor prothrombin complex concentrate (4F-PCC), andexanet alfa (AA), or idarucizumab. Among patients on DOAC who develop ICH, reversal with 4F-PCC, AA, or idarucizumab achieves high hemostatic success with low to moderate risk of all-cause mortality and thromboembolism. Head-to-head comparisons suggest similar reversal efficacy between AA and 4F-PCC. Findings support the effectiveness of available reversal strategies while underscoring the need for randomized trials to confirm comparative safety and longer-term outcomes."

Retrospective data • Review • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders

Real-world clinical decision of andexanet alfa administration for intracranial hemorrhage during anticoagulant therapy using factor Xa inhibitor. (PubMed, J Crit Care Med (Targu Mures)) - "We observed 63 cases of ICH in patients receiving anticoagulation therapy with apixaban, rivaroxaban, or edoxaban. Emergency surgical cases should also be eligible for andexanet alfa to ensure intraoperative safety. Further research is required to determine clinically appropriate indications for its use."

Journal • Real-world evidence • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders

Management of Direct Oral Anticoagulants in Adult Patients Undergoing Cardiac Surgery: Joint Consensus Statement by the Society of Cardiovascular Anesthesiologists and the Society of Thoracic Surgeons (STS 2026) - "Andexanet alfa is not recommended for emergency cardiac surgery where cardiopulmonary bypass is needed due to the risk of heparin resistance...For the direct thrombin inhibitor dabigatran, Idarucizumab may be considered first-line, with 4F-PCC as a second line therapy or even hemodialysis...This expert consensus provides guidance on the perioperative management of DOACs for adult patients undergoing cardiac surgery with the goal to enhance patient safety and outcomes. Table Image"

Clinical • Surgery • Anesthesia • Cardiovascular • Nephrology • Renal Disease

Prothrombin complex concentrate for oral factor Xa inhibitor-associated intracerebral hemorrhage. (PubMed, Res Pract Thromb Haemost) - "Although andexanet alfa, a specific FXaI antidote, demonstrated efficacy in andexenet alfa for acute intracerebral hemorrhage (ANNEXA-I) trial, it was associated with a high thromboembolic rate...Apixaban was the most frequent FXaI (86.6%), with atrial fibrillation as the main indication (94.3%)...4F-PCC achieved high hemostatic efficacy and low thromboembolic risk in FXaI-associated ICH. Mortality was comparable to ANNEXA-I, but thrombotic events were markedly lower, supporting current guideline recommendations for 4F-PCC use in this setting."

Journal • Atrial Fibrillation • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders • Thrombosis

DOACs, Andexanet, Pump Clots-Oh My! A Joint Consensus Statement for Safe Management of Patients on DOACs Requiring Cardiac Surgery. (PubMed, Anesth Analg) - No abstract available

Journal • Cardiovascular

CTA Spot Sign and Response to Andexanet in FXai-associated Intracerebral Hemorrhage: a Secondary Analysis of ANNEXa-I (ISC 2026) - "The presence of the spot sign and its features were significantly associated with HE in FXai-associated ICH. The treatment effect of andexanet was still consistent regardless of the presence of the spot sign and its features"

Cerebral Hemorrhage • Hematological Disorders

Timely Door-To-Reversal in Anticoagulation-Associated Intracranial Hemorrhage: Rate limiting steps and predictors in a Multicenter Observational Study. (ISC 2026) - "Overall, 81% were on FXa inhibitors and 19% on warfarin. Reversal agents included andexanet alpha (43%) and prothrombin complex concentrates (56%)... Similar to the acute ischemic stroke treatment timeline, reversal of anticoagulation in AA-ICrH was significantly faster when using a SA protocol, underscoring the critical role of streamlined emergency pathways using SA to improve DTR times. These observations highlight the need for targeted interventions to reduce delays and leverage the rapid onset of action of the approved reversal agents."

Clinical • Observational data • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Ischemic stroke

Early administration of andexanet alfa reduces hematoma expansion in factor Xa inhibitor-associated intracerebral hemorrhage (ISC 2026) - "This association tended to be consistent regardless of OTD time but was more pronounced in the patients with a shorter OTD time (Figure). The rate of favorable outcome was numerically higher in the andexanet alfa group but did not differ significantly between the two groups (53% vs 38%, adjusted odds ratio 2.45; 95%CI 0.89-6.72).Conclusions : Early administration of andexanet alfa inhibits hematoma expansion and might contribute to improved functional outcome in intracerebral hemorrhage patients associated with factor Xa inhibitors."

Cerebral Hemorrhage • Hematological Disorders

Andexanet Alfa versus 4F-PCC for Direct Anticoagulation Reversal in Intracranial Hemorrhage: A Quality Improvement Analysis (ISC 2026) - "In this real-world analysis, andexanet alfa was linked to a higher risk of significant intracranial hemorrhage growth than 4F-PCC, despite similar rates of neurological deterioration, thromboembolic events, functional disability, and mortality. 4F-PCC may serve as a clinically viable alternative for reversing FXa inhibitor anticoagulation in intracranial hemorrhage."

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