Adzynma (apadamtase alfa /cinaxadamtase alfa) / Takeda, Meiji Seika - LARVOL DELTA

ABO-dependent manner modulates hemostasis in neonatal thrombocytopenia via ADAMTS13-mediated VWF cleavage. (PubMed, Pediatr Neonatol) - "The VWF susceptibility to ADAMTS13 proteolysis was increased as follows: A, B and O blood phenotype during platelet transfusion, causing imbalance of neonatal hemostasis in an ABO-dependent manner."

Journal • Hematological Disorders • Targeted Protein Degradation • Thrombocytopenia

Successful Use of Recombinant ADAMTS13 in a Pregnant Patient with Immune-mediated Thrombotic Thrombocytopenic Purpura. (PubMed, J Thromb Haemost) - "We report the first case of immune-mediated thrombotic thrombocytopenic purpura (iTTP) successfully treated with recombinant ADAMTS13 (rhADAMTS13) during pregnancy. rhADAMTS13 could represent an effective, well-tolerated therapeutic alternative for iTTP patients with clinical or ADAMTS13 relapse. During pregnancy, where plasma exchange or caplacizumab are undesirable and recommendations are uncertain, this strategy could represent a promising therapeutic alternative in selected cases."

Journal • Hematological Disorders • Thrombocytopenic Purpura

ADAMTS13 variant (R1206K) exhibits increased VWF-cleaving activity and inhibition of thrombus formation under flow (ASH 2025) - "Our results demonstrate that we have identified a rADAMTS13 R1206K variant that exhibitsan enhanced enzymatic activity for cleaving a surrogate VWF peptide substrate and more physiologicalsubstrate such as multimeric VWF under static/denaturing and fluidic shear conditions. This rADAMTS13variant may be further explored for the treatment of TTP and other inflammatory thrombotic disordersassociated with relative deficiency of ADAMTS13 function."

Hematological Disorders • Thrombocytopenic Purpura • Thrombosis

Potential paradoxical hemostatic function of ADAMTS13 by enhancing collagen-induced platelet aggregation and activation (ASH 2025) - "Our findings revealed a novel but paradoxical function of rADAMTS13 promotinghemostasis while inhibiting thrombosis at the same time, like thrombin that has both prothrombotic andantithrombotic activities."

Cardiovascular • Hematological Disorders • Thrombocytopenic Purpura • Thrombosis • THBS2

Health state utility values in congenital thrombotic thrombocytopenic purpura (cTTP): A vignette-based valuation Study in the UK general population (ASH 2025) - "Vignette-based health states (HS) represented varying disease severities and treatments,including recombinant ADAMTS13 (rADAMTS13), plasma-based therapy (PBT) prophylaxis, and noprophylaxis...Several limitations should be noted: low scores even inasymptomatic states may reflect perceived long-term burden; and the online self-complete format mayhave limited participant understanding of treatment complexity. These values support the use of HRQoLin future evaluations of cTTP therapies."

Clinical • Hematological Disorders • Thrombocytopenic Purpura

Review of the management of patients with immune thrombotic thrombocytopenic purpura with persistently low adamts-13 activity - a challenge beyond rarity. (ASH 2025) - "7 patients were treated with caplacizumab and 1 with recombinantADAMTS13...Different immunosuppressive treatment combinations per patient: 2 patients: Corticosteroids+AntiCD201 patient: Corticosteroids+AntiCD20+Splenectomy4 patients: Corticosteroids+AntiCD20+Mycophenolate1 patient:Corticosteroids+AntiCD20+Mycophenolate+Daratumumab 1 patient: Corticosteroids+AntiCD20+Cyclosporine+Bortezomid1 patient: Corticosteroids+AntiCD20+Cyclosporine+Bortezomib+Splenectomy1 patient: Corticosteroids+Anti-CD20+Cyclosporine+Bortezomib+Mycophenolate.CONCLUSIONS - A small proportion of patients with iTTP don´t respond to first-line therapy and these individuals are athigh risk of relapse. A total of 11 patients meeting the specified criteria were identified, 7 women and 4 men. At diagnosis, the mean age was 43 years (range: 24–71). Laboratory parameters at presentation were:mean hemoglobin 9 g/dL (range: 6.5–12.7), mean platelet count 13.3 × 10³/mm³ (range: 5–22), and..."

Clinical • Review • Hematological Disorders • Thrombocytopenic Purpura • PROCR

Procedure-triggered late-onset congenital thrombotic thrombocytopenic purpura: Unmasking functional impact of a heterozygous synonymous ADAMTS13 variant (c.1716G>A) associated with reduced enzyme expression (ASH 2025) - "Congenital TTP should be considered in adult patients with recurrent thrombotic microangiopathy,especially when triggered by surgery or physiologic stress, and in the absence of a sustained inhibitorresponse. This case underscores the importance of recognizing the pathogenic potential of synonymousvariants and the need for expanded interpretation of ADAMTS13 genetic testing. Early recognition canprevent unnecessary PLEX and enable targeted therapy with plasma infusion or recombinant ADAMTS13.This case highlights a novel mechanism for late-onset cTTP and illustrates the serious implications ofdelayed diagnosis in adult patients."

Anemia • Cardiovascular • Diabetes • Gastroenterology • Hematological Disorders • Hypertension • Immune Thrombocytopenic Purpura • Metabolic Disorders • Myocardial Infarction • Thrombocytopenia • Thrombocytopenic Purpura

Recombinant ADAMTS13 prophylaxis in patients with congenital thrombotic thrombocytopenic purpura: Final analysis from A phase 3 randomized, controlled study (ASH 2025) - P3 | "No new safety concerns were identified and, despite a smallsample size owing to the rarity of cTTP, participants reported greater treatment satisfaction duringrADAMTS13 prophylaxis compared with PBT. These findings support the clinical benefit of rADAMTS13prophylaxis in patients with cTTP."

Clinical • P3 data • Hematological Disorders • Infectious Disease • Pediatrics • Thrombocytopenia • Thrombocytopenic Purpura

A case series of pediatric patients with congenital thrombotic thrombocytopenia purpura (cTTP) treated with recombinant ADAMTS13 (ASH 2025) - "All three children in our case series, two of whom were switched from FFP, havetolerated rADAMTS13 without any reactions and have not experienced any TTP flares. Labparameters for all patients remain improved since starting treatment. Our data supports thesafety and efficacy of rADAMTS13 in young children."

Clinical

Clinical management of congenital thrombotic thrombocytopenic purpura in Latin America: Expert consensus from a modified Delphi panel (ASH 2025) - "Assuming equal access to all prophylaxis options, panelists indicatedthat recombinant ADAMTS13 would be the first-line prophylactic treatment over FFP and overcryoprecipitate-poor plasma (100% for all patient populations).Key considerations for cTTP patients in remission deciding whether to initiate prophylaxis includetolerability of treatment (11/11; 100%) and financial costs associated with treatment and regular hospitalvisits (11/11; 100%). Panelists confirmed a need for local guidelines specific to cTTP treatment andmanagement (13/13; 100%).ConclusionsOur findings offer important insights into current cTTP clinical management practices in LATAM, and aregenerally consistent with the latest ISTH guidelines published after the Delphi panel was conducted. Thisconsensus outlines essential factors influencing treatment choices and patient care, with considerationof regional particularities, and may help to guide LATAM physicians caring for patients with cTTP."

Clinical • Cardiovascular • Hematological Disorders • Thrombocytopenic Purpura • Thrombosis

Expert consensus on the clinical management of congenital thrombotic thrombocytopenic purpura in Asia-Pacific: A modified Delphi panel (ASH 2025) - "Current treatments for managing acuteTTP episodes and prophylaxis involve ADAMTS13 supplementation by infusion of fresh frozen plasma(FFP), solvent/detergent-treated FFP, intermediate-purity plasma-derived factor VIII (FVIII) concentrate,and more recently, recombinant ADAMTS13 (rADAMTS13).Although international guidelines on the management of thrombotic microangiopathy and/or TTPfrequently include sections on cTTP, there is limited up-to-date guidance specifically on the clinicalmanagement of cTTP...Panelists agreed that patients would be more likely toaccept prophylactic treatment if it could be self-administered at home rather than HCP-administered inclinicals/hospitals (11/11; 100%).ConclusionsOur findings provide valuable insights into current practices in APAC and are consistent with the latestISTH guidelines which were published after the Delphi panel concluded. This consensus may help toguide physicians caring for patients with cTTP in APAC, outlining key..."

Clinical • Cardiovascular • Hematological Disorders • Thrombocytopenic Purpura • Thrombosis

Modern Management of Congenital Thrombotic Thrombocytopenic Purpura (cTTP) (ASH 2025) - "Supported By C Dr Alice Taylor will outline current updates on treatment strategies in congenital TTP, illustrating the evolution of treatment options in congenital TTP in recent years, from plasma and plasma-derived products to recombinant ADAMTS13...Beyond this, Dr. Taylor will discuss how we need to examine what clinical outcomes we are targeting beyond prevention of acute TTP relapse."

Hematological Disorders • Thrombocytopenic Purpura

The Changing Landscape of the Care of Patients With Immune-Mediated and Congenital TTP (ASH 2025) - "Supported By C Thrombotic thrombocytopenic purpura (TTP), once almost universally fatal, is now a condition with markedly improved survival due to advancements in diagnostics, therapeutic plasma exchange, immunosuppressive therapies, and novel therapies like caplacizumab and recombinant ADAMTS13...He will discuss the integration of caplacizumab, corticosteroids, rituximab, and other emerging agents, including strategies to balance rapid disease control with long-term remission goals...Beyond this, Dr. Taylor will discuss how we need to examine what clinical outcomes we are targeting beyond prevention of acute TTP relapse."

Clinical • Cardiovascular • Cognitive Disorders • Hematological Disorders • Thrombocytopenic Purpura

Reduced half-life of recombinant ADAMTS13 in a patient with cTTP undergoing total hip arthroplasty. (PubMed, Thromb J) - No abstract available

Journal • Hematological Disorders • Orthopedics • Thrombocytopenic Purpura

Recombinant ADAMTS-13 for congenital and immune thrombotic thrombocytopenic purpura in pregnancy. (PubMed, Blood Vessel Thromb Hemost) - "Here, we report 3 cases of TTP in pregnancy: 2 women with cTTP, treated throughout pregnancy with recombinant ADAMTS-13 (rADAMTS-13), and 1 with refractory iTTP, where rADAMTS-13 was used in place of ongoing plasma exchange. All pregnancies resulted in excellent fetomaternal outcomes."

Journal • Hematological Disorders • Thrombocytopenic Purpura

ADAMTS13 Protects Kidney Function in Alport Syndrome (KIDNEY WEEK 2025) - "In vivo, Col4a5-KO Alport mice were treated with bi-weekly administration of recombinant ADAMTS13 protein and kidney function was assessed...Conclusion Our findings reveal that endothelial metabolic dysfunction and ADAMTS13 downregulation contribute to microvascular injury and endothelial dysfunction in AS. These results suggest that ADAMTS13 restoration may serve as a promising therapeutic strategy to preserve endothelial function and slow CKD progression in AS, and potentially other forms of CKD."

Chronic Kidney Disease • Genetic Disorders • Metabolic Disorders • Renal Disease • COL4A5 • ICAM1 • VCAM1

RECOMBINANT HUMAN ADAMTS13 ATTENUATES LPS-INDUCED ACUTE KIDNEY INJURY AND RENAL MICROANGIOPATHY IN MICE WITH LIVER CIRRHOSIS VIA CLEAVAGE OF VWF (AASLD 2025) - "Administration of rADAMTS13 may improve inflammation, oxidative stress, and reduced blood flow in liver and kidney, thereby mitigating HRS."

Preclinical • Acute Kidney Injury • Fibrosis • Gastroenterology • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis • Liver Failure • Nephrology • Pneumonia • Renal Disease • Respiratory Diseases • ICAM1 • KIM1 • LCN2 • SELP • SPP1 • VCAM1

Real-world safety and efficacy of rADAMTS13 prophylaxis in congenital thrombotic thrombocytopenic purpura: experience from Polish patients previously treated with fresh frozen plasma. (PubMed, Haematologica) - "Not available."

Journal • Real-world evidence • Hematological Disorders • Thrombocytopenic Purpura

Advances in the diagnosis and treatment of thrombotic thrombocytopenic purpura (PubMed, Rinsho Ketsueki) - "For iTTP, the combination of therapeutic plasma exchange and immunosuppressive therapy with caplacizumab, an anti-VWF nanobody, has been shown to prevent early fatal thrombosis and reduce mortality. For cTTP, a phase III clinical trial demonstrated the efficacy and safety of recombinant ADAMTS13, which led to the coverage of this treatment by Japanese national health insurance."

Journal • Review • Cardiovascular • Hematological Disorders • Thrombocytopenic Purpura • Thrombosis

A Study of TAK-755 (rADAMTS13) With Little to No Plasma Exchange (PEX) Treatment in Adults With Immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP) (clinicaltrials.gov) - P2 | N=33 | Recruiting | Sponsor: Takeda | Active, not recruiting ➔ Recruiting

Enrollment open • Hematological Disorders • Thrombocytopenic Purpura

Long term follow-up outcomes in congenital thrombotic thrombocytopenic purpura. (PubMed, Blood) - "The majority of cTTP patients in the UK have now switched to recombinant ADAMTS13 (n=43, 58.9%), owing to inadequate symptom control (53.5%), plasma reactions (30.2%), or subclinical disease activity (16.3%). This work shows the breadth of ADAMTS13 genetic variants in cTTP, and demonstrates efficacy of regular prophylaxis in (i) reducing acute TTP episodes, and (ii) preventing end organ damage, but despite advances, cTTP related symptoms and the use of blood products, remained problematic."

Journal • Cardiovascular • CNS Disorders • Depression • Fatigue • Hematological Disorders • Mood Disorders • Pain • Psychiatry • Renal Disease • Thrombocytopenic Purpura

Kidney transplantation in congenital thrombotic thrombocytopaenic purpura: using recombinant ADAMTS13 to balance relapse and rejection. (PubMed, BMJ Case Rep) - "Finding an appropriate immunosuppressive regimen in cTTP transplant recipients can be challenging, as calcineurin inhibitors are associated with an increased risk of thrombotic microangiopathy (TMA), whereas prophylactic plasma exchange reduces the blood concentrations of mycophenolic acid and belatacept. Ultimately, he was treated with recombinant a disintegrin and metalloproteinase with a thrombospondin type one motif, member 13 (ADAMTS13) infusions, halting TMA and preventing future episodes. This is the first case of prophylaxis with recombinant ADAMTS13 in a kidney allograft recipient, illustrating its potential benefit over plasma exchange by assuring therapeutic immunosuppressants' concentrations and preventing both rejection and TMA-induced graft injury."

Journal • Hematological Disorders • Nephrology • Rare Diseases • Thrombocytopenic Purpura • Transplantation

Targeting hemostatic enzymes: from mechanistic insights to therapeutic frontiers. (PubMed, Curr Opin Hematol) - "Understanding hemostatic enzymatic regulation offers new avenues for risk stratification, diagnosis, and treatment of coagulation disorders. Although significant progress has been made, challenges remain in translating laboratory findings to clinical practice, necessitating further large-scale validation. Precision-guided enzymatic therapies hold promise for improving outcomes in acute care settings."

Journal • Cardiovascular • Hematological Disorders • Infectious Disease • Mood Disorders • Septic Shock

A microfluidic approach reveals ongoing disease activity in TTP patients despite clinical remission. (PubMed, J Thromb Haemost) - "We successfully used a flow-based assay to investigate VWF-dependent platelet recruitment as a rapid and sensitive monitoring tool for TTP patients, and an important research tool to study thrombogenesis. Our results using this assay, as a marker of ongoing microvascular thrombi formation, confirm the need to normalise ADAMTS13 activity levels in iTTP patients in clinical remission and the benefit of using recombinant ADAMTS13 in cTTP."

Journal • Hematological Disorders • Thrombocytopenic Purpura

Quantitative Systems Pharmacology Modeling of Platelet Responses to Recombinant ADAMTS13 in Patients With Congenital Thrombotic Thrombocytopenic Purpura. (PubMed, CPT Pharmacometrics Syst Pharmacol) - P3 | "These results provide confirmative evidence to support the use of rADAMTS13 in cTTP by integrating the current mechanistic understanding of interactions between ADAMTS13 and VWF multimers as its substrate, as well as key downstream parameters, primarily platelet count. Virtual patient clinical simulations from the QSP model supported the regulatory approval of rADAMTS13 in cTTP, highlighting the significant potential of QSP modeling to supplement clinical trial data in rare disease drug development."

Journal • Cardiovascular • Hematological Disorders • Rare Diseases • Thrombocytopenia • Thrombocytopenic Purpura • Thrombosis