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

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

Post Marketing Observational Study on Safety of BALFAXAR vs. KCENTRA for Reversal of Vitamin K Antagonist Induced Anticoagulation in Adults Undergoing Urgent Surgery or Invasive Procedure (clinicaltrials.gov) - P=N/A | N=3574 | Recruiting | Sponsor: Octapharma | Not yet recruiting ➔ Recruiting | Initiation date: Jun 2024 ➔ Jan 2025

Enrollment open • Trial initiation date

EFFICACY AND SAFETY OF HIGH-DOSE FOUR-FACTOR PROTHROMBIN COMPLEX CONCENTRATE: LEX-209 SUBANALYSIS (SCCM 2025) - P3 | "Introduction: The LEX-209 Phase 3 randomized controlled trial of investigational four-factor prothrombin complex concentrate (4F-PCC; Octaplex®/Balfaxar®, Octapharma) demonstrated hemostatic non-inferiority to the FDA-approved control 4F-PCC (Beriplex®/Kcentra®, CSL Behring) in rapid vitamin K antagonist (VKA) reversal before urgent surgery (p< 0.001). Investigational 4F-PCC, administered at the maximum permitted dose, appeared to be safe and effective for rapid VKA reversal in urgent surgery patients with significant bleeding risk. These findings further support the use of high-dose 4F-PCC for surgical patients needing rapid VKA reversal."

Clinical • Hematological Disorders

RARE CASE OF ACQUIRED CLOTTING FACTOR INHIBITOR FROM BLADDER CANCER (SCCM 2025) - "He received 7units of FFP, 2PRBC, Vitamin-K and KCENTRA over the first few days but hematuria and coagulopathy did not improve...He was started on steroids and Factor eight inhibitor bypass activity (FEIBA) treatment for ACFI...Treatment is 3 prong; 1) correct coagulopathy 2) replenish blood loss 3) stabilize/treat immune dyscrasia. Factor V inhibitors are rare but may arise from exposure to topical fibrin glues or bovine thrombin preparations that contain bovine factor V. Early recognition, confirmation and therapy initiation of ACFI is key to ensuring positive outcome and to avoid complications from life threatening bleed"

Clinical • Bladder Cancer • Cardiovascular • Genito-urinary Cancer • Hematological Disorders • Hematological Malignancies • Hypertension • Immunology • Lung Cancer • Mood Disorders • Oncology • Rheumatology • Solid Tumor • Urology

COMPARISON OF TWO DIFFERENT FIXED-DOSE FACTOR EIGHT INHIBITOR BYPASSING ACTIVITY (FEIBA) REGIMENS IN THE MANAGEMENT OF WARFARIN-ASSOCIATED COAGULOPATHIES. (WRMC 2025) - "Kcentra is the only FDA approved PCC for managing warfarin associated coagulopathies, but Factor VIII Inhibitor Bypass Activity (FEIBA) is commonly used in its place. Conclusions Our new FEIBA dosing recommendations resulted in more individuals achieving the post-FEIBA administration INR goal. Authors plan to finalize data collection and analysis in the coming months."

Cardiovascular

Evaluation of Fixed Dosing vs Weight Based Dosing of Kcentra in Intracranial Hemorrhage caused FactorXaInhibitors (ASHP 2024) - No abstract available

Cerebral Hemorrhage • CNS Disorders • Hematological Disorders

Evaluation of Four Factor Prothrombin Complex Kcentra Use at a Tertiary Care Medical Center (ASHP 2024) - No abstract available

Evaluation of BE1116 in Patients With Traumatic Injury and Acute Major Bleeding to Improve Survival ( TAP Study ) (clinicaltrials.gov) - P3 | N=1370 | Terminated | Sponsor: CSL Behring | N=8000 ➔ 1370 | Trial completion date: Sep 2026 ➔ Oct 2024 | Recruiting ➔ Terminated | Trial primary completion date: Sep 2026 ➔ Oct 2024; Study terminated due to business reasons and slow enrollment. No safety issues were found.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination

Addition of PCC Does Not Improve the Performance of rTEG or ACT in the Measurement of Dabigatran Concentration. (ASA 2024) - "This was repeated with the addition of 1 unit/mL of PCC (KCentra, CSL Behring, Kong of Prussia, PA) to each sample. The addition of prothrombotic precursors did not improve the accuracy of either test in the determination of concentration of dabigatran. ACT or rTEG may be useful POCTs for use with dabigatran anticoagulation for CPB"

Atrial Fibrillation • Cardiovascular • Hematological Disorders • Thrombosis

SPONTANEOUS RETROPHARYNGEAL HEMATOMA WITH THE USE OF APIXABAN (CHEST 2024) - "Given his positive history of Apixaban use, IV Decadron and Kcentra were administered...While most cases of RPHs have been associated with traumatic injuries, spontaneous cases have also been reported especially in patients on warfarin and rarely on rivaroxaban... Patients developing spontaneous RPH on warfarin are often switched to direct oral anticoagulants (DOAC). However, reinitiation of anticoagulation in patients with spontaneous RPH due to DOACs remains a challenge due to rare occurrence and hence limited literature."

Atrial Fibrillation • Cardiovascular • Endocrine Disorders • Gastrointestinal Disorder • Hypertension • Obstructive Sleep Apnea • Otorhinolaryngology • Pain • Pulmonary Disease • Respiratory Diseases • Sleep Disorder