Kcentra (plasma-derived prothrombin complex concentrate) / CSL Behring - LARVOL DELTA

Efficacy and Safety of 4F-PCC (4-Factor Prothrombin Complex Concentrate) in Adult Patients Undergoing Complex Cardiovascular Surgery With Cardiopulmonary Bypass (CPB) (clinicaltrials.gov) - P3 | N=200 | Recruiting | Sponsor: CSL Behring | Trial completion date: Jun 2027 ➔ Dec 2026 | Trial primary completion date: May 2027 ➔ Nov 2026

Trial completion date • Trial primary completion date • Cardiovascular

HEMORRHAGIC RENAL ANGIOMYOLIPOMA AND FULMINANT DISSEMINATED INTRAVASCULAR COAGULATION IN A SECOND TRIMESTER PREGNANCY (WRMC 2026) - "She was given 89 units of blood products, including pRBCs, FFP, PPP, cryoprecipitate, PCC/Kcentra, albumin, and vitamin K. The patient was intubated and placed on four pressors for severe hemodynamic instability...Our case highlights the exceptionally rare presentation of a hemorrhagic renal angiomyolipoma in a young, pregnant patient who then developed DIC, underwent emergency cesarean section, received 89 blood products, four pressor therapies, and mechanical ventilation. CT Abdomen & Pelvis showing a large hematoma in the right retroperitoneum measuring 19.1 x 9.8 cm."

Hematological Disorders • Kidney Cancer • Oncology • Renal Cell Carcinoma • Septic Shock • Solid Tumor • ER

NOVEL ACTIVATED PROTHROMBIN COMPLEX CONCENTRATE REGIMEN FOR MANAGING WARFARIN-ASSOCIATED COAGULOPATHIES (WRMC 2026) - "Kcentra and Balfaxar are the only FDA approved PCC for managing warfarin-associated coagulopathies, but Factor VIII Inhibitor Bypass Activity (FEIBA) is commonly used in practice. The new FEIBA dosing regimen resulted in more individuals achieving a post-FEIBA INR ≤ 1.5. In comparison to other published studies, our population had higher baseline INR values and did not concomitantly receive clotting factor containing products. Our findings support the administration of low-fixed dose FEIBA in the management of warfarin-associated coagulopathies."

Hematological Disorders • Oncology

Efficacy and Safety of 4F-PCC (4-Factor Prothrombin Complex Concentrate) in Adult Patients Undergoing Complex Cardiovascular Surgery With Cardiopulmonary Bypass (CPB) (clinicaltrials.gov) - P3 | N=200 | Recruiting | Sponsor: CSL Behring | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular

In brief: Andexanet alfa (Andexxa) withdrawn. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal

Door-to-Needle Times for Intracerebral Hemorrhage in the Setting of Anticoagulation Reversal: Impact of a Bedside Kcentra Model (ASHP 2025) - No abstract available

Cerebral Hemorrhage • Hematological Disorders

Fixed Versus Weight-Based Kcentra Dosing for Anticoagulation Reversal: A Pre-Post Implementation Study of Utilization, Effectiveness, and Safety (ASHP 2025) - No abstract available

Clinical

Time to Kcentra administration with the presence of ED pharmacist (ASHP 2025) - No abstract available

Evaluation of Balfaxar vs Kcentra for Warfarin Reversal at an Academic Medical Center (ASHP 2025) - No abstract available

Evaluating reversal strategies for long-acting factor XI antibodies: RFVIIa®, FEIBA®, Kcentra®, novel FXI mutants, and an anti-idiotypic antibody (ASH 2025) - "BAY1831865), and theactive site binding FXIa inhibitor osocimab...With contact activation (ellagic acid or kaolin), the relative potency of thrombin inhibitionshifted: AB011 again showed the strongest inhibition on par with FXI-/- plasma, followed by gruticibart,and osocimab... FXI inhibitors produce anticoagulant effects across global coagulation assays that can bepartially or completely reversed by bypassing agents, particularly NovoSeven® and FEIBA®; however PT,TGA and viscoelastic testing also reveal the potential to generate a transient procoagulant/prothromboticstate if plasma concentrations of these commercially available agents are too high. The magnitude of theprocoagulant activity is dependent on the bypassing agent as well as the specific FXI inhibitor, suggestingthat reversal strategies should be tailored to the mechanism of the different FXI inhibitors (i.e. A2, A3, orcatalytic domain) to achieve optimal outcomes."

Hematological Disorders • Hemophilia • Rare Diseases

Prothrombin complex concentrate in managing direct oral anticoagulant (DOAC)-associated bleeding and real-world use in vitamin k antagonist (VKA)-associated bleeding: The ongoing lex-210 and lex-212 studies (ASH 2025) - P, P3 | "The LEX-212 study aims to assess the safety of Balfaxar vs. a comparator 4F-PCC(Kcentra/Beriplex, CSL Behring) for the urgent reversal of VKA-induced anticoagulation in real-worldsurgical settings, complementing evidence from clinical trials.Study Design and LEX-210 (NCT04867837) is a Phase 3, multicenter, prospective, double-blinded, group‑sequential, parallel-group, adaptive design study with a preplanned interim analysis for potential sample size modification.Approximately 260 patients aged ≥18 years with acute major bleeding while on FXaI therapy will berandomized 1:1 to receive low-dose (15 IU/kg) or high-dose (50 IU/kg) 4F-PCC, with the aim to include atleast 91 evaluable patients in each group in the full analysis set (FAS). LEX-212 isconducted in the US; the study started in Q1 2025 and has one site initiated and 14 patients enrolled sofar, with the study end expected in Q2 2032. These studies will expand the understanding of 4F-PCCs inthe context of..."

Clinical • Real-world • Real-world evidence • Cardiovascular

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

Spontaneous Ischemic Proctitis in an Elderly Male on Anticoagulation (ACG 2025) - "We presented a rare case of spontaneous ischemic proctitis in a 95-year-old male on therapeutic anticoagulation.Case Description/ A 95-year-old male with severe aortic stenosis (deferred AVR), CKD stage II, advanced dementia, and recent left lower extremity DVT recently started on apixaban 9 days earlier who presented after a witnessed large-volume melanic stool...In the emergency department he received pRBCs, IV pantoprazole, and Kcentra...Mesalamine suppositories were initiated...Diagnosis requires endoscopy and biopsy for confirmation. Management primarily includes supportive care, hemostasis, and withdrawal of inciting agents with additional mesalamine for potentially symptomatic relief.Figure: Flexible sigmoidoscopy, at the level of the proximal rectum, showing a characteristic "single stripe sign" of ulceration and friability classically seen in ischemic colitis.Figure: Flexible sigmoidoscopy, at the level of the distal rectum, showing worsening..."

Clinical • Alzheimer's Disease • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Dementia • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immunology

Hemostatic Efficacy of Prothrombin Complex Concentrate for Managing Coagulopathic Bleeding in Surgical Patients: Results from the LEX-209 and LEX-211 (FARES-II) Phase 3 Trials (AABB 2025) - P3 | "The LEX-209 and LEX-211 Phase 3 randomized controlled trials assessed the efficacy and safety of investigational PCC (Octaplex/Balfaxar) in patients undergoing urgent VKA reversal or cardiac surgery with elevated INR. Study Design/ LEX-209 (NCT02740335) was a double-blind, non-inferiority trial comparing investigational vs. control PCC (Beriplex/Kcentra) in adults (≥18 years) with INR ≥2.0 receiving VKAs prior to urgent surgery... PCC administration demonstrated rapid INR correction in VKA-associated coagulopathy vs. control PCC and significantly greater INR reduction following CPB-associated coagulopathy vs. FP."

Clinical • P3 data • Acute Kidney Injury • Cardiovascular • Hematological Disorders • Nephrology • Renal Disease

A STORM IN THE BRAIN: REVERSIBLE CEREBRAL VASOCONSTRICTION SYNDROME PRESENTING AS INTRACEREBRAL HEMORRHAGE: A CASE REPORT (CHEST 2025) - "Kcentra was given for Eliquis reversal...Due to the high suspicion of RCVS, the patient was initiated on Nimodipine 60mg every 6 day for 1 week, 60mg every 8 hrs/day for the next week, 60mg twice daily for the following week, and 60mg once a day for last week, with improvement in her symptoms. The patient's home medication, Effexor, was reduced by 50%, given its vasoconstriction properties, and weaned off by the second week... This case indicates it is crucial to include RCVS in the differential diagnosis of sudden-onset headaches and seizures, as treatment is moderately benign. Therefore, early diagnosis is essential to prevent complications of this reversible neurological disease."

Case report • Clinical • Cardiovascular • Cerebral Hemorrhage • Chronic Obstructive Pulmonary Disease • Endocrine Disorders • Epilepsy • Hematological Disorders • Immunology • Inflammatory Arthritis • Migraine • Respiratory Diseases • Thrombosis • Vasculitis

Anesthetic Management of a PVC Ablation Complicated by Pericardial Tamponade and Subsequent Embolic Stroke (ASA 2025) - "Coagulopathy was treated with Kcentra, FFP, TXA, NovoSeven, and platelets to reverse anticoagulant effects and restore hemostasis. Given persistent neurological decline, extubation was delayed, prompting neuroimaging that revealed multiple acute strokes. Multimodal resuscitation and coagulation management were critical in stabilizing this patient for postoperative neurological assessment."

Anesthesia • Cardiovascular • CNS Disorders • Dyslipidemia • Hematological Disorders • Hypertension • Ischemic stroke • Multiple Sclerosis

Management for Urgent Femur Fixation in a Post-Lung Transplant Patient on Apixaban with CKD and Distorted Neuraxial Anatomy (ASA 2025) - "As surgical timing approached the 72-hour threshold for increased hip fracture mortality, four-factor PCC (Kcentra) was administered. General anesthesia was administered, and the procedure continued uneventfully. The patient was discharged without complications."

Clinical • Anesthesia • Atrial Fibrillation • Cardiovascular • Chronic Kidney Disease • Infectious Disease • Musculoskeletal Diseases • Nephrology • Orthopedics • Pneumonia • Renal Disease • Respiratory Diseases • Transplantation

Fixed-Dose Four-Factor Prothrombin Complex Concentrate for Reversal of Anticoagulation: Evaluation of Efficacy, Safety, and Cost Savings. (PubMed, J Hematol) - "The median cost savings of fixed-dosing per patient on warfarin and DOACs were $1,567 and $3,936, respectively, with annualized median hospital cost savings of $176,239 and $146,733, respectively. Fixed-dosing of 4F-PCC had significantly less cost than adjusted dose and is associated with similar rates of thrombosis and death compared to other studies."

HEOR • Journal • Cardiovascular • Hematological Disorders • Thrombosis

Efficacy and Safety of 4F-PCC (4-Factor Prothrombin Complex Concentrate) in Adult Patients Undergoing Complex Cardiovascular Surgery With Cardiopulmonary Bypass (CPB) (clinicaltrials.gov) - P3 | N=200 | Not yet recruiting | Sponsor: CSL Behring

New P3 trial • Cardiovascular

Biochemical analysis of anticoagulant compounds in four-factor prothrombin complex concentrates (ISTH 2025) - "Aims To characterize pro- and anticoagulant content of three 4F-PCCs, Prothromplex (PKT; Takeda), Kcentra (KCT; CSL Behring), and Octaplex (OTX; Octapharma), and explore the effect of 4F-PCC heparin content on thrombin generation in vitro. Following heparin removal, PKT resulted in the highest increase in peak thrombin in normal plasma; in anticoagulated plasma, similar thrombin levels were observed for all 4F-PCCs. Table or Figure Upload"

Temporal Effects of 4F-PCC and ATIII in Mitigating TBI Induced BBB Permeability and Hemorrhage (ISTH 2025) - "Methods In Vitro: The trans-endothelial electrical resistance of thrombin challenged brain microvascular endothelial cell (BEC) monolayers was measured after treatment with 4F-PCC (Kcentra, CSL Behring) or Antithrombin-III (ATIII; Kybernin, CSL Behring)...One way ANOVA, Holm-Sidak’s post-hoc multiple comparison test, comparisons as indicated on the graph, ***p<0.001 n=5-10 per group. Table or Figure Upload"

Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Inflammation • Vascular Neurology

Use of Andexanet Alpha Versus Standard of Care Among Patients Hospitalized With Upper and Lower Gastrointestinal Bleeding: A Retrospective, Multicenter, Comparative Effectiveness Study (ATS 2025) - "Patients who present with a gastrointestinal bleed (GIB) while on rivaroxaban or apixaban may receive reversal agents such as protein complex concentrate (PCC; KCentra) or Andexanet alfa (AA). In this retrospective, multicenter comparative effectiveness study, there were no differences in time to mortality in patients who received AA compared to those who received PCC. However, effect estimates for mortality, thromboembolic events, and need for transfusion all favored PCC over AA. Figure 1."

HEOR • Retrospective data • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Fibrosis • Gastroenterology • Hematological Disorders • Hepatology • Immunology

OPSTAHT: Administration of Prothrombin Complex Concentrate vs. Standard Transfusion During/After Heart Transplantation (clinicaltrials.gov) - P3 | N=14 | Terminated | Sponsor: University of Maryland, Baltimore | N=60 ➔ 14 | Recruiting ➔ Terminated; Standard practice change prohibited enrollment

Enrollment change • Trial termination • Cardiovascular • Heart Failure • Transplantation

Successful Urgent Liver Transplantation in a High-Risk Patient on Therapeutic Apixaban: A Complex Case of End-Stage Liver Disease and Hepatocellular Carcinoma with Portal Vein Thrombosis (IARS-SOCCA 2025) - "Their suggestion was low molecular weight heparin as first line and vitamin K antagonists (Warfarin) be used as second line...Given apixaban use and the patient's ESLD and CKD3b, a multidisciplinary team discussed apixaban reversal with anti-inhibitor coagulant complex (FEIBA) vs prothrombin complex concentrate [human] (Kcentra); our institution has removed the FDA approved reversal agent for Xa inhibitors (recombinant Factor Xa) from formulary...Once the portal clamp was removed, one gram of tranexamic acid was administered...This case highlights the complexities of managing therapeutic anticoagulation with apixaban in urgent LT. Patients with ESLD are at high risk for any major surgery due to significant coagulopathy; however, in the setting of liver transplantation, a fine balance exists. In the prehepatic and anhepatic phases, it is important to minimize blood loss from the surgical perspective as well as adequately resuscitate without exacerbating venous..."

Clinical • Anesthesia • Atrial Fibrillation • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Hepatitis C • Hepatocellular Cancer • Hepatology • Hypertension • Hypotension • Infectious Disease • Ischemic stroke • Nephrology • Oncology • Solid Tumor • Thrombosis • Transplantation • Venous Thromboembolism