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

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

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

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."

PROS1

Andexanet alfa for the reversal of anticoagulation: Dutch practice data (ISTH 2025) - "Background Andexanet alfa, a reversal agent for factor Xa inhibitors (rivaroxaban and apixaban), has been shown to be effective in achieving hemostasis in two recent clinical trials. Pending additional data, a more comprehensive investigation into the nature of the thrombotic events will be conducted. Table or Figure Upload"

Atrial Fibrillation • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Gastrointestinal Disorder • Hematological Disorders • Mood Disorders • Venous Thromboembolism

Insights from an anticoagulant-related major bleeding registry: review of care practices (ISTH 2025) - "Patients who received one of the following antidotes for bleeding were identified using prescription lists: prothrombin complex concentrate (PCC), andexanet alfa or idarucizumab. During these consultations, a statement of discussion on management of modifiable risk factors for rebleeding was recorded in 31 (59%). Table or Figure Upload"

Review • Cardiovascular • Venous Thromboembolism

Perioperative On-Demand Reversal with Andexanet How to Monitor Reversal and When to Reanticoagulate (ISTH 2025) - "Background We present the first reported surgical case of an 82-year-old patient admitted to our hospital with mechanical ileus and extremely high apixaban concentrations of 540 ng/mL. In the first critical hours after DOAC reversal with andexanet, the viscoelastic RVV-test strongly correlates with the modified anti-FXa assay. Table or Figure Upload"

An Audit to Assess Andexanet Alfa for Major Bleeding with Factor Xa Inhibitors (ISTH 2025) - "Aims To review andexanet alfa for reversing anticoagulation from apixaban or rivaroxaban in adults with life-threatening or uncontrolled gastrointestinal bleeding, and assess compliance to national and local guidance To determine the efficacy of andexanet alfa by measuring clinical outcomes Background Direct oral anticoagulants (DOACs) are increasingly used for various indications due to its favourable efficacy and safety profiles. 2 thrombotic events (2 ischaemic strokes) occurred during admission. No thrombotic events occurred within 90 days of recent hospital admission."

Cardiovascular • Gastroenterology • Hematological Disorders • Ischemic stroke

Use of andexanet alfa for direct oral anticoagulant reversion: a retrospective study in a tertiary h (ISTH 2025) - "Andexanet alfa (AA), a modified recombinant inactive form of factor X, has been approved for reversing the effects of the factor Xa inhibitors rivaroxaban and apixaban. Other deviations included failure to administer an infusion following the bolus dose (1 case) and the use of AA for unapproved indications (2 cases). Table or Figure Upload"

Retrospective data • Atrial Fibrillation • Cardiovascular • Hematological Disorders • Ischemic stroke • Myocardial Infarction • Thrombosis

Reversal therapy of anti-Xa oral anticoagulats: more on of Andexanet alfa vs. 4F-PCC (ISTH 2025) - "Aims This study evaluates the efficacy, safety, and clinical outcomes of AA versus 4-factor prothrombin complex concentrate (4F-PCC) in managing acute major bleeding related to apixaban or rivaroxaban. Multivariable regression showed positive correlation between hematoma expansion and neurosurgery (r= -0.30, p=0.031) and between 30-day outcome and type of hemorrhage (r=0.25, p=0.017). Table or Figure Upload"

Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders

Real-world utilisation of Andexanet-Alfa: A single centre experience (ISTH 2025) - "Background Since its approval by NICE, Andexanet-alfa has been integrated into protocols for the reversal of apixaban and rivaroxaban in life-threatening or uncontrolled gastrointestinal bleeding (GIB) across England. Effective haemostasis was achieved in 9 cases (75%) of those with a life-threatening GIB. Delays in the administration of Andexanet-alfa from the time of its approval were seen in 5 cases (25%), with patients waiting between 6 and 18 hours and 9 patients (45%) were given the incorrect dosing regimen."

Clinical • Real-world • Real-world evidence • Cardiovascular • Gastroenterology • Hematological Disorders • Thrombosis

Valuable chromogenic assay to assess the efficacy of the reversal by Andexanet-alpha (ISTH 2025) - "Aims The aim of this study is to evaluate the efficacy of low range anti-Xa assays for the measurement of residual DiXaI concentration (Apixaban and Rivaroxaban) after reversal by Andexanet-alpha. Results The large sample dilution in standard range assay results in the dissociation of Andexanet-alpha from the DiXaI leading to an overestimation of the DiXaI level, as described previously for other chromogenic assays. In contrast, the low range assays on all analyzers permit accurate measurement of residual DiXaI with a concentration below the cut-off (50 ng/mL) as expected with reversal therapy."

Clinical • Cardiovascular

Real-world pharmacovigilance study of thrombotic events with Andexanet Alfa using FAERS database (ISTH 2025) - "Aims Our study aims to analyze thrombotic adverse events associated with Andexanet Alfa using a post-marketing pharmacovigilance database Background On May 3rd, 2018, the US FDA granted accelerated approval to Andexanet Alfa as an antidote to reverse major bleeding associated with Apixaban and Rivaroxaban. Summary of baseline characteristics and ROR is detailed in Table 1 and Table 2. Table or Figure Upload"

Adverse events • Clinical • Real-world • Real-world evidence • Cardiovascular • Hematological Disorders • Myocardial Infarction • Peripheral Arterial Disease • Thrombosis

Platelet-dependent hemostatic potential in the presence of DOACs (ISTH 2025) - "Healthy donor blood was compared with DOAC-treated blood (600 nM rivaroxaban, 300 nM edoxaban or 800 nM apixaban) in presence or absence of nanobodies against specific DOACs or andexanet. The inhibitory effects were counteracted by DOAC-specific nanobodies which restored fibrin area for 85% (84-87%, all P>0.9999 compared to control). Andexanet-alfa demonstrated a similar reversal, suggesting that the nanobodies and andexanet-alfa are equal in restoring coagulant function."

Atrial Fibrillation • Cardiovascular • Venous Thromboembolism

Accurate measurement of edoxaban concentration after reversal by andexanet alpha (ISTH 2025) - "Background Direct oral anticoagulants (DOACs) such as rivaroxaban, apixaban, and edoxaban are commonly used for preventing and treating thromboembolic disorders. The low range assay obtained accurate measurement results of edoxaban with a residual concentration below the cut-off as expected with reversal therapy. The tendencies of the results with the low range assay were consistent across analyzers."

Cardiovascular

Safe and effective reversal of enoxaparin with andexanet alfa in healthy volunteers and in patients with acute major bleeding (ISTH 2025) - "Background Andexanet alfa (andexanet) is the only approved reversal agent for acute major bleeding in apixaban or rivaroxaban treated patients. Good or excellent hemostasis at 12 hours was achieved in 14 of 16 patients (88%) in whom this could be assessed. Table or Figure Upload"

Clinical • Hematological Disorders

Specific reversal of factor Xa inhibitors with single domain antibodies (ISTH 2025) - "Aims To develop and validate single-domain antibodies (sdAbs) for the highly specific reversal of edoxaban, apixaban and rivaroxaban...Andexanet-alpha, the only approved reversal treatment for factor Xa inhibitors, can prevent hematoma expansion in haemorrhaging patients but increases thrombosis risk due to its cross-reactivity with TFPI and heparan sulphate-antithrombin complexes...Mouse tail bleeding time was prolonged (more than 10 min) by edoxaban treatment, which was reversed to 2 min in mice treated with both edoxaban and anti-edoxaban sdAbs, matching the tail bleeding time of untreated mice (1E). Table or Figure Upload"

Cardiovascular • Hematological Disorders • Thrombosis

Concentration-time course of Apixaban after a massive overdose and repetitive treatment with Andexanet alfa – a case report (Euroanaesthesia 2025) - "No effect could be detected on unbound apixaban concentrations or elimination. OndexxyaR appears to be effective also in massive overdosing, but may necessitate repeated administration. Combination with eliminatory strategies (e.g. plasmapheresis) might be reasonable."

Case report • Clinical • Atrial Fibrillation • Cardiovascular • Hematological Disorders

Transfusion and mortality within 24 hours after major trauma in patients with direct-acting oral anticoagulants (Euroanaesthesia 2025) - "DOACs have gradually replaced warfarin due to favorable efficacy and safety profiles...Only one such agent (idarucizumab for dabigatran) is used in Sweden, while administration of andexanet alfa (for reversal of apixaban, edoxaban and rivaroxaban) is not endorsed by national recommendations since proof of benefit has not been presented compared to administration of prothrombin complex concentrate.The aims were to analyze if patients treated with DOACs presenting with major trauma were more likely to receive blood transfusions, and if they had a higher mortality rate within the first 24 hours after hospital admission, compared to patients with no anticoagulant medication.Materials and This was a single-center, retrospective study...Mortality within 24 hours was observed in 6/47 (13%) patients in the DOAC group compared to 17/222 (8%) in the matched non-DOAC group, OR 1.69 (95% CI 0.62 to 4.58). Erythrocytes transfusion was required in 18 (38%) patients among the cases..."

Clinical • Anesthesia

The place of andexanet alfa in the management of intracerebral haemorrhage in patients taking anti-Xa oral anticoagulants (Euroanaesthesia 2025) - No abstract available

Clinical