2,587 results match your criteria Hemophilia Type A

Novel vectors and approaches for gene therapy in liver diseases.

JHEP Rep 2021 Aug 30;3(4):100300. Epub 2021 Apr 30.

Gene Therapy Area, Foundation for Applied Medical Research, University of Navarra, IdisNA, Pamplona, Spain.

Gene therapy is becoming an increasingly valuable tool to treat many genetic diseases with no or limited treatment options. This is the case for hundreds of monogenic metabolic disorders of hepatic origin, for which liver transplantation remains the only cure. Furthermore, the liver contains 10-15% of the body's total blood volume, making it ideal for use as a factory to secrete proteins into the circulation. Read More

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Similar sports participation as the general population in Dutch persons with haemophilia; results from a nationwide study.

Haemophilia 2021 Jun 19. Epub 2021 Jun 19.

Van Creveldkliniek, University Medical Center Utrecht, Utrecht, The Netherlands.

Introduction: Although sports participation is advocated in people with haemophilia (PWH), detailed data concerning sports participation in Dutch PWH is lacking.

Aim: to assess sports participation in Dutch PWH (6-65 years) compared to the Dutch general population (GP).

Methods: Data from a nationwide, cross-sectional study in PWH were analysed. Read More

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Considerations on Activity Assay Discrepancies in Factor VIII and Factor IX Products.

J Thromb Haemost 2021 Jun 17. Epub 2021 Jun 17.

Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.

New modified coagulation factor VIII (FVIII) and factor IX (FIX) products have been designed to improve the treatment of individuals with hemophilia A and B by increasing the interval between dosing. Although these FVIII and FIX molecules have been structurally modified to improve the circulation time, the changes have also influenced their behavior in functional assays in comparison with traditional plasma-derived or recombinant coagulation factors. The assignment of potencies for these products can be problematic because discordance in factor activity values between the commonly used one-stage clotting (OC) and chromogenic substrate (CS) assays is often observed. Read More

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Acquired Hemophilia A Presenting with Infectious Aortic Aneurysms Due to an Underlying Helicobacter Cinaedi Infection: A Case Report.

Intern Med 2021 Jun 12. Epub 2021 Jun 12.

Department of Hematology, Asahi General Hospital, Japan.

Acquired hemophilia A (AHA) is a bleeding disorder caused by the acquired appearance of inhibitor for factor VIII. Approximately half of all patients with AHA have some type of underlying disease. We herein report the case of a 72-year-old Japanese man with AHA who presented with infectious aortic aneurysms due to an underlying Helicobacter cinaedi infection. Read More

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Does Cost-Effectiveness Analysis Overvalue Potential Cures? Exploring Alternative Methods for Applying a "Shared Savings" Approach to Cost Offsets.

Value Health 2021 Jun 10;24(6):839-845. Epub 2021 May 10.

The Institute for Clinical and Economic Review, Boston, MA, USA. Electronic address:

Objectives: To evaluate alternative methods to calculate and/or attribute economic surplus in the cost-effectiveness analysis of single or short-term therapies.

Methods: We performed a systematic literature review of articles describing alternative methods for cost-effectiveness analysis of potentially curative therapies whose assessment using traditional methods may suggest unaffordable valuations owing to the magnitude of estimated long-term quality-adjusted life-year (QALY) gains or cost offsets. Through internal deliberation and discussion with staff at the Health Technology Assessment bodies in England and Canada, we developed the following 3 alternative methods for further evaluation: (1) capping annual costs in the comparator arm at $150 000 per year; (2) "sharing" the economic surplus with the health sector by apportioning only 50% of cost offsets or 50% of cost offsets and QALY gains to the value of the therapy; and (3) crediting the therapy with only 12 years of the average annual cost offsets or cost offsets and QALY gains over the lifetime horizon. Read More

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The B-Natural study-The outcome of immune tolerance induction therapy in patients with severe haemophilia B.

Haemophilia 2021 Jun 12. Epub 2021 Jun 12.

Indiana Haemophilia and Thrombosis Centre, Indianapolis, Indiana, USA.

Introduction: Inhibitors develop less frequently in haemophilia B (HB) than haemophilia A (HA). However, when present, the success of tolerization by immune tolerance induction (ITI) therapy is lower and the risk of complications higher.

Aim: To evaluate the use and outcome of ITI in patients with HB and inhibitors. Read More

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Deletion of Coagulation Factor IX Compromises Bone Mass and Strength: Murine Model of Hemophilia B (Christmas Disease).

Calcif Tissue Int 2021 Jun 12. Epub 2021 Jun 12.

Medical Research Service, Portland Veterans Affairs Health Care System, 3710 SW US Veterans Hospital Road, Portland, OR, 97239, USA.

Osteopenia and osteoporosis have increasingly become a recognized morbidity in those persons with hemophilia (PwH) receiving inadequate prophylactic clotting factor replacement. Animal models can control or eliminate genetic and environmental factors and allow for invasive testing not clinically permissible. Here, we describe the skeletal phenotype of juvenile and adult male mice with a genetically engineered deficiency in coagulation factor IX (FIX KO). Read More

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Fusion of engineered albumin with factor IX Padua extends half-life and improves coagulant activity.

Br J Haematol 2021 Jun 9. Epub 2021 Jun 9.

Department of Life Sciences and Biotechnology and LTTA Centre, University of Ferrara, Ferrara, Italy.

The short half-life of coagulation factor IX (FIX) for haemophilia B (HB) therapy has been prolonged through fusion with human serum albumin (HSA), which drives the neonatal Fc receptor (FcRn)-mediated recycling of the chimera. However, patients would greatly benefit from further FIX-HSA half-life extension. In the present study, we designed a FIX-HSA variant through the engineering of both fusion partners. Read More

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A Foot to Last a Lifetime-Is Hindfoot Fusion Ever Appropriate for Pediatric Orthopaedic Conditions?

Derek M Kelly

J Pediatr Orthop 2021 Jul;41(Suppl 1):S39-S46

Campbell Clinic Orthopaedics, Memphis, TN.

Introduction: Hindfoot deformities in the pediatric population can be painful and result in severe limitations. Although arthrodesis is known to relieve pain, there are concerns over its use because of the risk that adjacent joint degenerative disease could result, leading to a new source of pain, dysfunction, and additional surgical procedures later in life.

Methods: A literature review of hindfoot fusions in children focused on articles with the highest levels of evidence and those of particular historical significance. Read More

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Monitoring of von Willebrand factor inhibitors in patients with type 3 von Willebrand disease using a quantitative assay.

Connie H Miller

Haemophilia 2021 Jun 5. Epub 2021 Jun 5.

Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Background: Antibodies inhibiting von Willebrand factor (VWF) develop in a subset of patients with type 3 von Willebrand disease (VWD3) and may be detected by their inhibition of ristocetin cofactor activity (VWF:RCo). Some also inhibit factor VIII activity (VIII:C).

Aim: To describe monitoring of ten VWD3 patients for VWF inhibitors using a quantitative assay. Read More

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Personalised Prophylaxis in a Child with Haemophilia A and Type 1 Diabetes.

Clin Pract 2021 May 8;11(2):287-292. Epub 2021 May 8.

Hemophilia Foundation of Salta, Salta 4400, Argentina.

Poor management of either type 1 diabetes or haemophilia A can lead to complications such as organ dysfunction and haemarthropathy. Here, we describe the case of an 8-year-old boy diagnosed with severe haemophilia A shortly after birth. At 2 years old, he was also diagnosed with type 1 diabetes. Read More

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An analysis of member retention patterns for adult rare disease cohorts to support evaluating multiyear payment arrangements for novel therapies.

J Manag Care Spec Pharm 2021 Jun;27(6):753-759


Traditionally, treatment for chronic conditions addressed symptoms or was disease modifying and required lifelong periodic administration and recurring costs. Cell and gene therapies for rare diseases often require a short administration period relative to their expected long-term clinical benefit. Costs have historically been recognized when the service or treatment is administered, resulting in the potential for the cost associated with the possible long-term clinical benefit of cell and gene therapies being incurred during a short administration period. Read More

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Real-world cost estimates of initiating emicizumab in US patients with haemophilia A.

Haemophilia 2021 May 29. Epub 2021 May 29.

The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA.

Introduction: Emicizumab is the first approved non-factor therapy for haemophilia A. It provides superior prophylactic bleeding control compared to other products in both patients with and patients without inhibitors. However, there is no real-world data about the monetary consequences of starting emicizumab. Read More

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Soft tissue releasing and serial casting for management of flexion contracture after primary total knee arthroplasty in a patient with hemophilia.

Int J Surg Case Rep 2021 May 21;83:105995. Epub 2021 May 21.

Department of Orthopedics, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand. Electronic address:

Introduction And Importance: Flexion contracture following total knee arthroplasty (TKA) in patients with hemophilia is not uncommon, and this complication reduces knee range of motion and produces morbidity for the patient. This report states the success of treatment of flexion contracture after primary TKA in a patient with hemophilia; by open soft tissue contracture releasing and serial casting.

Case Presentation: A 20-year-old-man presented with hemophilia type A. Read More

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Hemophilia and type 1 diabetes: not as black as it is painted-a case report.

Acta Diabetol 2021 May 28. Epub 2021 May 28.

Department of Pediatrics, Medical University of Warsaw, 02-091, Warsaw, Poland.

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Illness perceptions and their relation to physical activity in children and adolescents with hemophilia.

Health Psychol Behav Med 2020 Oct 4;8(1):461-474. Epub 2020 Oct 4.

Université de Montréal, Montreal, Canada.

Hemophilia is a rare bleeding disorder in which illness perceptions have seldom been studied. Illness perceptions are important in predicting patients' behavior. Due to the risk of bleeding and joint damage, healthcare professionals often discourage some physical activities. Read More

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October 2020

HLA Variants and Inhibitor Development in Hemophilia A: A Retrospective Case-Controlled Study Using the ATHNdataset.

Front Med (Lausanne) 2021 7;8:663396. Epub 2021 May 7.

Hemostasis Branch, Division of Plasma Protein Therapeutics, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, United States.

In hemophilia A (HA) patients, gene-defects as genetic risk-factors for developing inhibitors to Factor VIII have been extensively studied. Here we provide estimates of inhibitor-risk associated with the patient's Human Leukocyte Antigen (HLA). We used next generation sequencing for high-resolution HLA Class II typing of 997 HA patients. Read More

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Inflammation, angiogenesis and sensory nerve sprouting in the synovium of bony ankylosed and not bony ankylosed knees with end-stage haemophilic arthropathy.

Haemophilia 2021 May 22. Epub 2021 May 22.

Department of Orthopedic Surgery, The First Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.

Introduction: Clinical practice showed that patients with haemophilia (PwH) with bony ankylosed end-stage haemophilic arthropathy knees reported milder pain than those with not bony ankylosed knees.

Aim: To compare the differences in pain sensation and the histopathological differences in synovial samples of affected knee joints between PwH with bony ankylosed end-stage haemophilic arthropathy knees and those with not bony ankylosed knees.

Methods: From January 2011 to December 2019, the synovial samples of knee joints were collected during total knee arthroplasty (TKA) surgery for end-stage haemophilic arthropathy. Read More

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Non-Human Glycans Can Regulate Anti-FVIII Antibody Formation in Mice.

Blood 2021 May 21. Epub 2021 May 21.

Brigham and Women's Hosptial, Boston, Massachusetts, United States.

Recombinant Factor VIII (FVIII) products represent a life-saving intervention for patients with hemophilia A. However, patients can develop antibodies against FVIII that prevent FVIII function and directly increase morbidity and mortality. The development of anti-FVIII antibodies varies depending on the type of recombinant product employed, with previous studies suggesting that 2nd generation baby hamster kidney (BHK)-derived FVIII products display greater immunogenicity than 3rd generation Chinese hamster ovary (CHO)-derived FVIII. Read More

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Clinicopathological features of hemophilia in a tertiary care centre of India.

J Family Med Prim Care 2021 Jan 30;10(1):295-299. Epub 2021 Jan 30.

Department of Pathology, IMS, BHU, Varanasi, Uttar Pradesh, India.

Context: Inherited bleeding disorders are common in India and hemophila and von Willebrand diseases are the most common among them. These patients can present in any department including paediatrics, medicine, orthopaedics and even gynaecology so knowledge about hemophilias and facilities for specialized tests for diagnosis are required. Few centres of north-eastern part of India perform these tests so hemophilias remain an underdiagnosed and underreported disease. Read More

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January 2021

Terminal half-life of FVIII and FIX according to age, blood group and concentrate type: Data from the WAPPS database.

J Thromb Haemost 2021 May 20. Epub 2021 May 20.

Van Creveldkliniek, University Medical Centre Utrecht, Utrecht, The Netherlands.

Background: Real-life data on pharmacokinetics of factor (F) VIII/IX concentrates, especially extended half-life (EHL), concentrates in large cohorts of persons with hemophilia are currently lacking.

Objectives: This cross-sectional study aimed to establish reference values for terminal half-life (THL) for FVIII/IX concentrates according to concentrate type, age, blood group and inhibitor history.

Patients/methods: Data were extracted from the Web-Accessible Population Pharmacokinetics Service database. Read More

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Treatment of high-risk bleeding with susoctocog alfa in a patient with acquired haemophilia A and a nosocomial severe acute respiratory syndrome coronavirus 2 infection.

Eur J Hosp Pharm 2021 May 19. Epub 2021 May 19.

Pharmacy, Complexo Hospitalario Universitario A Coruna, A Coruna, Spain.

We report the case of a man in his early 70s with idiopathic acquired haemophilia A and persistent high-titre type II inhibitors on immunosuppressive treatment to eradicate the inhibitor. As complications, he had a nosocomial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which caused severe pneumonia and an explosive inflammatory reaction that required tocilizumab and remdesivir treatment, and a high-risk retroperitoneal haematoma. Recombinant porcine factor VIII, susoctocog alfa, was requested from the Pharmacy Service in view of the extreme risk of thromboembolism resulting from the concomitant inflammatory storm caused by SARS-CoV-2. Read More

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Performance of a clinical risk prediction model for inhibitor formation in severe haemophilia A.

Haemophilia 2021 May 14. Epub 2021 May 14.

Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.

Background: There is a need to identify patients with haemophilia who have a very low or high risk of developing inhibitors. These patients could be candidates for personalized treatment strategies.

Aims: The aim of this study was to externally validate a previously published prediction model for inhibitor development and to develop a new prediction model that incorporates novel predictors. Read More

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Gene therapy in PIDs, hemoglobin, ocular, neurodegenerative, and hemophilia B disorders.

Open Life Sci 2021 3;16(1):431-441. Epub 2021 May 3.

Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Guangxi University, Nanning, 530004, China.

A new approach is adopted to treat primary immunodeficiency disorders, such as the severe combined immunodeficiency (SCID; e.g., adenosine deaminase SCID [ADA-SCID] and IL-2 receptor X-linked severe combined immunodeficiency [SCID-X1]). Read More

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The Possible Non-Mutational Causes of FVIII Deficiency: Non-Coding RNAs and Acquired Hemophilia A.

Front Med (Lausanne) 2021 15;8:654197. Epub 2021 Apr 15.

Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.

Hemophilia type A (HA) is the most common type of blood coagulation disorder. While the vast majority of cases are inherited and caused by mutations in the gene, recent data raises new questions regarding the non-heritability of this disease, as well as how other molecular mechanisms might lead to the development of HA or increase the severity of the disease. Some data suggest that miRNAs may affect the severity of HA, but for some patients, miRNA-based interference might cause HA, in the absence of an mutation. Read More

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A mutation in SLC37A4 causes a dominantly inherited congenital disorder of glycosylation characterized by liver dysfunction.

Am J Hum Genet 2021 06 7;108(6):1040-1052. Epub 2021 May 7.

Complex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA.

SLC37A4 encodes an endoplasmic reticulum (ER)-localized multitransmembrane protein required for transporting glucose-6-phosphate (Glc-6P) into the ER. Once transported into the ER, Glc-6P is subsequently hydrolyzed by tissue-specific phosphatases to glucose and inorganic phosphate during times of glucose depletion. Pathogenic variants in SLC37A4 cause an established recessive disorder known as glycogen storage disorder 1b characterized by liver and kidney dysfunction with neutropenia. Read More

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Coexistence of Acquired Hemophilia and Antiphospholipid Serology in Monoclonal Gammopathy Patient.

Int Med Case Rep J 2021 28;14:261-264. Epub 2021 Apr 28.

Department of Internal Medicine, Groupe Hospitalier Sud-Ile de France, Melun, 77000, France.

Acquired hemophilia is a rare coagulopathy with hemorrhage into the skin, muscle, or soft tissues and mucous membranes and caused by inhibitor antibodies, mainly against FVIII. We report a case of acquired hemophilia presenting with diffuse cutaneous hemorrhage and hemothorax. The patient was found to have acquired an FVIII inhibitor and a high titer of anti β2 glycoprotein 1 IgG and IgM, and anticardiolipin IgM in the context of IgA kappa-type monoclonal gammopathy. Read More

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Characteristics, complications, and sites of bleeding among infants and toddlers less than 2 years of age with VWD.

Blood Adv 2021 04;5(8):2079-2086

Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA.

Data on infants and toddlers (ITs) with von Willebrand disease (VWD) are lacking. We used data collected in the US Hemophilia Treatment Center Network (USHTCN) to describe birth characteristics, bleeding episodes, and complications experienced by 105 patients with VWD who were <2 years of age. In 68% of the patients, the reason for diagnostic testing was a family history of a bleeding disorder. Read More

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Patient selection for hemophilia gene therapy: Real-life data from a single center.

Res Pract Thromb Haemost 2021 Mar 14;5(3):390-394. Epub 2021 Mar 14.

Hemostasis and Thrombosis Unit Division of Hematology Cliniques Universitaires Saint-Luc Université Catholique de Louvain (UCLouvain) Brussels Belgium.

Background: While the number of individuals with hemophilia who are expected to be or have already been included in gene therapy trials has been regularly reported, the number of unscreened or excluded individuals, in addition to the reasons for exclusion, is mostly not reported.

Methods: We conducted an eligibility assessment of all people with severe hemophilia for gene therapy trials in one large Belgian hemophilia treatment center based on patient selection criteria of gene therapy trials and patients' profiling.

Results: Among 87 adult patients with severe hemophilia A and B, 11 aged ≥65 years and two women were excluded from analysis. Read More

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First observation of inhibitor development against efmoroctocog alfa in France.

Transfus Apher Sci 2021 Apr 8:103128. Epub 2021 Apr 8.

Department of Paediatrics, Clinical and Molecular Haemostasis, Frankfurt University Hospital, Frankfurt am Main, Germany.

In patients with severe haemophilia receiving clotting factor concentrates, the risk of immunisation against their usual treatment is still patent and feared. New haemophilia drug treatments with an extended half-life have become available over the past few years. The risk of inhibitor development to these new treatments is unclear. Read More

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