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

Association of Biomarkers with risk of Hematoma Expansion and Arterial Thromboembolic Events in Acute Factor Xa Inhibitor-Associated Intracerebral Hemorrhage: The ANNEXa-I Biomarker Substudy (ISC 2025) - "We examined the association between change from baseline to 1 hour in anti-FXa level and endogenous thrombin potential (ETP) and outcome in patients with apixaban- or rivaroxaban-associated intracerebral hemorrhage (ICH). We compared the effects of andexanet with usual care on change in biomarker levels between baseline and 1 hour using Wilcoxon rank sum test. In patients with factor Xa inhibitor-associated ICH, andexanet compared with usual care produces greater reduction in anti-FXa and greater increase in ETP at 1 hour. Both reduction in anti-FXa and increase in ETP between baseline and 1 hour are independent predictors of HE but do not predict ATE."

Biomarker • Late-breaking abstract • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders

Restarting anticoagulation in FXa inhibitor associated intracerebral hemorrhage treated with andexanet reduces thrombotic events (ISC 2025) - "Treatment with prophylactic or therapeutic anticoagulation is associated with a reduced risk of thrombotic events in patients with FXa inhibitor-associated major bleeding receiving andexanet."

Late-breaking abstract • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders • Ischemic stroke • Myocardial Infarction • Venous Thromboembolism

Con: Andexanet alfa is Preferred over PCC for Reversal of FXa Inhibitor Associated ICH (ISC 2025) - No abstract available

Cerebral Hemorrhage

Pro: Andexanet alfa is Preferred over PCC for Reversal of FXa Inhibitor Associated ICH (ISC 2025) - No abstract available

Cerebral Hemorrhage

Andexanet-induced Heparin Resistance in Cardiac Surgery - A Rapid Review of Case Reports and Series. (PubMed, J Thromb Haemost) - "Andexanet alfa, a Food and Drug Administration (FDA)-approved antidote for apixaban and rivaroxaban, is used to manage life-threatening or uncontrolled bleeding...Nafamostat mesylate was used in some cases reported from Japan Heparin resistance following andexanet exposure poses significant procoagulant risk during CPB. Preemptive high-dose antithrombin therapy may improve ACT values. Further studies are needed to understand the mechanisms and optimize management of this condition."

Journal • Cardiovascular • Hematological Disorders • Thrombosis

Correction of the effect of direct oral and parenteral anticoagulants in hemorrhagic stroke (PubMed, Zh Vopr Neirokhir Im N N Burdenko) - "Early hemostatic therapy and reversal of anticoagulant effects in patients with hemorrhagic stroke significantly reduce the risk of adverse outcomes. This problem is being studied. Regular literature review with creation of updated clinical guidelines is needed."

Journal • Review • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders • Thrombocytopenia

Prothrombin complex concentrate for reversal of oral anticoagulants in patients with oral anticoagulation-related critical bleeding: a systematic review of randomised clinical trials. (PubMed, Scand J Trauma Resusc Emerg Med) - "Among participants with VKA or DOAC-related critical bleeding, evidence from randomised clinical trials is currently insufficient to establish if PCC is superior or inferior versus other interventions in decreasing the risk of undesirable patient-relevant outcomes or improving health-related quality of life."

Journal • Review

Clinical guidelines for a dry land: challenges in developing recommendations for DOAC management in emergent cardiac surgery. (PubMed, Eur J Cardiothorac Surg) - No abstract available

Clinical guideline • Journal • Cardiovascular

Andexanet alfa: trials just leave us with more questions. (PubMed, Res Pract Thromb Haemost) - "It did, however, show an increased risk of thrombosis, predominantly stroke with andexanet alfa. In this perspective, I reflect on some of the key criticisms of the trial and the implications for its interpretation."

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

Andexanet alfa for oral fxa inhibitor-associated major acute intracerebral hemorrhage: insights into clinically relevant thromboembolic events from the ANNEXA-I study. (PubMed, J Vasc Bras) - No abstract available

Journal • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders

Andexanet alfa in patients with factor Xa inhibitor associated intracranial hemorrhage: the prospective observational multicenter ASTRO-DE study. (PubMed, Int J Stroke) - "ASTRO-DE is the first prospective observational study systematically collecting standardized clinical routine data with andexanet alfa treatment. The study demonstrated favorable hemo-stasis and minimal mean hematoma volume growth in patients with ICH associated with apixa-ban or rivaroxaban treatment."

Journal • Observational data • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders

Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage. (PubMed, Am J Ther) - No abstract available

Journal • Cerebral Hemorrhage • Hematological Disorders

Anticoagulation Reversal in Intracerebral Hemorrhage: A Case Report on the Efficacy of Andexanet Alfa in an Apixaban-Treated Patient. (PubMed, Cureus) - "This report highlights the potential of andexanet alfa for effective anticoagulation reversal in critical ICH cases while also addressing associated thrombotic risks. It underscores the need for a multidisciplinary approach and emphasizes the importance of further research to refine treatment strategies for anticoagulated patients with ICH."

Journal • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders

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 • Gastrointestinal Disorder • 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

A Case Report of Extra-pericardial Tamponade From a Low-Level Fall. (PubMed, Cureus) - "He was also on chronic medications, including apixaban and aspirin. This case highlights the complexities of polypharmacy and the medical challenges posed by the reversal agent andexanet alpha. Expanding mediastinal hematomas causing obstructive shock are rare, with most literature describing posterior rather than anterior mediastinal hematomas, particularly in cases resulting from a simple fall."

Journal • Cardiovascular • Chronic Obstructive Pulmonary Disease • Hematological Disorders • Immunology • Infectious Disease • Musculoskeletal Diseases • Orthopedics • Pain • Pneumonia • Pulmonary Disease • Respiratory Diseases

The efficacy and safety of andexanet alfa in the treatment of anticoagulation-related major bleedings: An Italian perspective. (PubMed, Thromb Res) - No abstract available

Journal • Cardiovascular • Hematological Disorders • Thrombosis

Andexanet alfa for the management of severe bleeding: what should critical care physicians know about it? (PubMed, Crit Care Sci) - No abstract available

Journal • Critical care

Troubleshooting heparin resistance. (PubMed, Hematology Am Soc Hematol Educ Program) - "Multiple causes of apparent heparin resistance include hypercoagulability, antithrombin deficiency, andexanet alfa used for direct oral anticoagulant reversal, thrombocytosis, and antiphospholipid antibody syndromes. Treatment options for managing patients with heparin resistance include weight-based dosing and administration of additional UFH, antithrombin supplementation, or the use of an alternative anticoagulant such as the direct thrombin inhibitors bivalirudin or argatroban."

Journal • Review • Critical care • Hematological Disorders • Infectious Disease • Inflammation • Novel Coronavirus Disease • Thrombocytosis

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

ASTRO-DE: Andexanet Alfa: Non-interventional Study in Stroke Units in Germany (DE) (clinicaltrials.gov) - P=N/A | N=141 | Active, not recruiting | Sponsor: University Hospital, Essen | Trial completion date: Dec 2024 ➔ Mar 2025

Trial completion date • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders

Management of severe traumatic brain injury in a rivaroxaban overdose: illustrative case. (PubMed, J Neurosurg Case Lessons) - "Routine reversal strategies may be insufficient in achieving hemostasis in rivaroxaban overdose. PLEX reduced serum rivaroxaban concentration by 52%. PLEX can be an important adjunct to consider for medical and perioperative management of rivaroxaban overdose. https://thejns.org/doi/10.3171/CASE24475."

Journal • CNS Disorders • Hematological Disorders • Vascular Neurology

(Management Case Study) Integration of Electronic Health Records with Voice-Activated Technology to Enhance Pharmacy Workflows (ASHP 2024) - "The alerts were designed to notify pharmacists at the order verification workstation and pharmacy technicians in the sterile compounding area in real-time once a medication order for a bleed reversal agentsuch as andexanet alfa, idarucizumab, protamine, and prothrombin complex concentrate [human]was signed and pended for verification by a pharmacist. The integration of voice-activated technology with EHR significantly enhanced the efficiency of pharmacy workflows at the community hospital. The system improved the prioritization and timely administration of critical medications, demonstrating a substantial reduction in processing times and enhancing patient safety. This approach can serve as a model for other healthcare institutions aiming to optimize their pharmacy operations through advanced technological integrations."

Case study • Clinical

Andexanet Alfa and FourFactor Prothrombin Complex Concentrate 4FPCC for the Reversal of Rivaroxaban and ApixabanAssociated Intracranial Hemorrhages (ASHP 2024) - No abstract available

Cerebral Hemorrhage • CNS Disorders • Hematological Disorders

Clinical Assessment of Andexanet Alfa for the Reversal of LifeThreatening Bleed at a Health System in New Jersey (ASHP 2024) - No abstract available

Clinical