26,615 results match your criteria Factor VIII


Identification of a modified coagulation factor X with enhanced activation properties as potential hemostatic agent.

Blood Cells Mol Dis 2021 Apr 23;89:102570. Epub 2021 Apr 23.

Research and Development, CSL Behring Innovation GmbH, Marburg, Germany.

Hemophilia A and hemophilia B are X-linked inherited bleeding disorders caused by a deficiency of coagulation factor VIII and IX, respectively. Standard of care is prophylactic factor replacement therapy; however, the development of neutralizing antibodies against these factors represents serious complications underlining the need for alternative treatment approaches. Human coagulation factor X has a central role within the blood coagulation system making it an attractive target for the development of alternative treatment strategies for patients with hemophilia. Read More

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Alpha 2-antiplasmin deficiency in a Sudanese child: a case report.

J Med Case Rep 2021 May 7;15(1):238. Epub 2021 May 7.

Hematology Department, Faculty of Medical Laboratory Sciences, Port Sudan Ahlia College, Port Sudan, Sudan.

Background: The plasma serine protease inhibitor alpha 2-antiplasmin (α-AP, otherwise known as α-plasmin inhibitor) is a rapid-acting plasmin inhibitor recently found in human plasma, which seems to have a significant role in the regulation of in vivo fibrinolysis. Congenital deficiency of α-AP is extremely uncommon.

Case Presentation: We report here a case of absolute deficiency of α-AP in an 11-year-old Sudanese boy, who had a lifelong intermittent hemorrhagic tendency (gum bleeding, epistaxis, and exaggerated bleeding after trauma). Read More

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Which tests can most effectively indicate the clinical phenotype of paediatric haemophilia patients with prophylaxis?

Blood Coagul Fibrinolysis 2021 Jun;32(4):259-265

Department of Pediatric Hematology.

Patients with haemophilia A who have similar FVIII levels show clinical heterogeneity, and 10-15% of patients with severe haemophilia do not have a severe bleeding phenotype. The aim of this study was to assess whether global haemostasis tests, such as thrombin generation assay (TGA) and thromboelastography (TEG), can predict the bleeding pattern of severe haemophilia better than trough levels and pharmacokinetic profiles, particularly in the prophylactic setting. The study group consisted of 39 patients with haemophilia A and 75 healthy controls. Read More

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Comparative analysis of the pivotal studies of extended half-life recombinant FVIII products for treatment of haemophilia A.

Haemophilia 2021 May 6. Epub 2021 May 6.

Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.

The need to reduce the burden of injections, and improve adherence and clinical outcomes in haemophilia A led to the development of recombinant FVIII products endowed with an extended plasma half-life (EHL-rFVIII) in comparison with standard half-life products (SHL-rFVIII). Lack of head-to-head studies makes difficult to grasp the relative value of each treatment option. We conducted a combined evaluation of the individual pivotal trials in order to assess between-product differences regarding the reported efficacy results and FVIII consumption. 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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Laparoscopic Hepatectomy for the Patient with Hemophilia A with High Titer Factor VIII Inhibitor.

Acta Med Okayama 2021 Apr;75(2):199-204

Department of Gastroenterological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences.

We present the first case of laparoscopic left lateral segmentectomy for hepatocellular carcinoma (HCC) in a patient with hemophilia A, acquired hepatitis C, and high-titer factor VIII inhibitor, which was confirmed by preoperative diagnosis. He underwent laparoscopic left lateral segmentectomy with the administration of recombinant activated factor VII. Surgery could be performed with reduced intraoperative hemorrhage. Read More

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Distinguishing Alzheimer's Disease Patients and Biochemical Phenotype Analysis Using a Novel Serum Profiling Platform: Potential Involvement of the VWF/ADAMTS13 Axis.

Brain Sci 2021 Apr 30;11(5). Epub 2021 Apr 30.

Department of Neurology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.

It is important to develop minimally invasive biomarker platforms to help in the identification and monitoring of patients with Alzheimer's disease (AD). Assisting in the understanding of biochemical mechanisms as well as identifying potential novel biomarkers and therapeutic targets would be an added benefit of such platforms. This study utilizes a simplified and novel serum profiling platform, using mass spectrometry (MS), to help distinguish AD patient groups (mild and moderate) and controls, as well as to aid in understanding of biochemical phenotypes and possible disease development. Read More

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Rehabilitation management of a triceps surae muscle injury in a young male with haemophilia A and high-titre inhibitors.

Acta Biomed 2021 Apr 30;92(S1):e2021118. Epub 2021 Apr 30.

Hemophilia Center, University Hospital of Padua, Padua, Italy.

Haemophilia A is a rare inherited hematologic disorder characterized by a deficit of coagulation factor VIII. It is associated with frequent episodes of musculoskeletal bleedings that occur mainly inside joints and secondly inside muscles. The majority of intramuscular hematomas respond well to conservative protocols, based on rehabilitation techniques and appropriate haemostatic coverage; surgery is limited to refractory cases. Read More

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A Rare Cause of Isolated Prolonged Activated Partial Thromboplastin Time: An Overview of Prekallikrein Deficiency and the Contact System.

J Investig Med High Impact Case Rep 2021 Jan-Dec;9:23247096211012187

MetroWest Medical Center, Framingham, MA, USA.

Prekallikrein (PK) deficiency, also known as Fletcher factor deficiency, is a very rare disorder inherited as an autosomal recessive trait. It is usually identified incidentally in asymptomatic patients with a prolonged activated partial thromboplastin time (aPTT). In this article, we present the case of a 52-year-old woman, with no prior personal or family history of thrombotic or hemorrhagic disorders, who was noted to have substantial protracted aPTT through the routine coagulation assessment before a kidney biopsy. Read More

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CAR and TRuC redirected regulatory T cells differ in capacity to control adaptive immunity to FVIII.

Mol Ther 2021 Apr 30. Epub 2021 Apr 30.

Herman B Wells Center for Pediatric Research, Indiana University, Indianapolis, IN 46202. Electronic address:

Regulatory T cells (Treg) control immune responses in autoimmune disease, transplantation, and enable antigen-specific tolerance induction in protein replacement therapies. Tregs can exert a broad array of suppressive functions through their T cell receptor (TCR) in a tissue-directed and antigen-specific manner. This capacity can now be harnessed for tolerance induction by "redirecting" polyclonal Tregs to overcome low inherent precursor frequencies and simultaneously augment suppressive functions. Read More

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Case Report: Multiple Cavernous Pericardial Lymphangioma (Pericardial Lymphangiomatosis) in a Captive Peregrine Falcon ().

Front Vet Sci 2021 14;8:662157. Epub 2021 Apr 14.

Departamento de Sanidad Animal, Facultad de Veterinaria, Instituto de Ganadería de Montaña (CSIC-ULE), Universidad de León, León, Spain.

A 12-year-old female peregrine falcon () from a private raptor breeding facility that presented a good body condition, died suddenly without showing previous symptoms. At necropsy, in the coelomic cavity, multiple cystic structures demarcated by a thin transparent wall and filled with a serous content were observed. They were firmly adhered to the cranial part of the epicardium and adjacent tissues and occupied the entire thoracic area of the coelomic cavity. Read More

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Frequency and Prognosis of Epidermal Growth Factor Receptor Variant III Mutations in Glioblastoma Multiforme among Indian Patients: A Single-Institution Study.

South Asian J Cancer 2020 Jul 26;9(3):126-129. Epub 2021 Apr 26.

Department of Medical Oncology and Hematology, Cancer Institute, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India.

 Glioblastoma multiforme (GBM) is a disease with poor outcome. Alterations or mutations in epidermal growth factor receptors (EGFRs) are found in GBM and may be targeted to improve outcomes.  We analyzed the frequency of EGFR variant III (vIII) mutations in patients with GBM and their outcomes after standard treatment. Read More

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Impact of Adrenal Function on Hemostasis/Endothelial Function in Patients Undergoing Surgery.

J Endocr Soc 2021 May 23;5(5):bvab047. Epub 2021 Mar 23.

Division of Endocrinology, Diabetes and Clinical Nutrition, Luzerner Kantonsspital, 6000 Luzern, Switzerland.

Context: Glucocorticoids regulate hemostatic and endothelial function, and they are critical for adaptive functions during surgery. No data regarding the impact of adrenal function on hemostasis and endothelial function in the perioperative setting are available.

Objective: We assessed the association of adrenal response to adrenocorticotropic hormone (ACTH) and markers of endothelial/hemostatic function in surgical patients. Read More

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RTK Inhibitors in Melanoma: From Bench to Bedside.

Cancers (Basel) 2021 Apr 2;13(7). Epub 2021 Apr 2.

Laboratory of Oncology and Experimental Surgery, Institut Jules Bordet, Université Libre de Bruxelles, 1000 Brussels, Belgium.

MAPK (mitogen activated protein kinase) and PI3K/AKT (Phosphatidylinositol-3-Kinase and Protein Kinase B) pathways play a key role in melanoma progression and metastasis that are regulated by receptor tyrosine kinases (RTKs). Although RTKs are mutated in a small percentage of melanomas, several receptors were found up regulated/altered in various stages of melanoma initiation, progression, or metastasis. Targeting RTKs remains a significant challenge in melanoma, due to their variable expression across different melanoma stages of progression and among melanoma subtypes that consequently affect response to treatment and disease progression. Read More

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An in vitro pharmacodynamic spiking study of befovacimab, a tissue factor pathway inhibitor monoclonal antibody, in blood samples from patients with severe FVIII deficiency.

Haemophilia 2021 Apr 29. Epub 2021 Apr 29.

Coagulation Advancement Laboratory, Department of Pharmacotherapy & Outcomes Sciences, Virginia Commonwealth University (VCU) School of Pharmacy, Richmond, VA, USA.

Introduction: Tissue factor pathway inhibitor (TFPI) is an endogenous protein that inhibits the extrinsic (tissue factor) pathway and negatively regulates thrombin production during coagulation. Inhibiting TFPI may become a useful target for haemophilia drug development to allow greater thrombin generation without use of the intrinsic (contact) pathway.

Aims: The in vitro effects of befovacimab, a humanized TFPI neutralizing antibody, were studied in whole blood and plasma samples from patients with severe FVIII deficiency. Read More

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FVIII inhibitors display FV-neutralising activity in the prothrombin time assay.

J Thromb Haemost 2021 Apr 29. Epub 2021 Apr 29.

National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Herts, EN6 3QG.

Background: The coagulation factors (F)V and VIII are homologous proteins that support haemostasis through their regulation of factor X (FX) activity. Haemophilia A (HA) patients have reduced FVIII activity and a prolonged bleeding time that is corrected through the administration of exogenous FVIII. Around a third of severe HA patients develop FVIII neutralising antibodies, known as 'inhibitors', that neutralise FVIII activity and preclude them from further FVIII therapy. Read More

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Anesthetic Management of Von Willebrand Disease in Pregnancy: A Retrospective Analysis of a Large Case Series.

Anesth Analg 2021 Apr 29. Epub 2021 Apr 29.

From the Department of Anesthesiology, Perioperative and Pain Medicine.

Background: Although Von Willebrand disease (vWD) is the most common heritable bleeding disorder, there are limited reports regarding the safety of neuraxial anesthesia in the obstetric population and no definitive guidelines specifying recommended pretreatment or therapies for patients with vWD. The aim of this study is to describe the anesthetic management of pregnant patients with vWD at a large tertiary-care center.

Methods: In this retrospective analysis, the study population was identified from vWD patients evaluated by our high-risk obstetric anesthesia consultation service and by diagnosis codes from our institutional research database registry. Read More

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Optimizing language for effective communication of gene therapy concepts with hemophilia patients: a qualitative study.

Orphanet J Rare Dis 2021 Apr 28;16(1):189. Epub 2021 Apr 28.

BioMarin Pharmaceutical Inc., Novato, CA, USA.

Background: For communities of people living with hemophilia and other genetic conditions, gene therapy could represent a paradigm shift in treatment strategies. As investigational therapeutic modalities such as gene therapy become more widely used and discussed, there is a critical need for all stakeholders to communicate using a lexicon that is intelligible, accurate, consistent, and representative of novel treatments. In doing so, expectations can be more carefully managed and potential risks, benefits, and limitations better understood. Read More

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Gene therapy may not be as expensive as people think: challenges in assessing the value of single and short-term therapies.

J Manag Care Spec Pharm 2021 May;27(5):674-681

Novartis Gene Therapies, Inc., Bannockburn, IL.

At an upfront price of $2.125 million, the one-time gene therapy onasemnogene abeparvovec for spinal muscular atrophy, a rare neuromuscular disorder that is usually fatal by 2 years of age if untreated, has been called the "most expensive drug ever." This flawed characterization raises important methodological and policy issues regarding valuation of high-cost treatments. Read More

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[Acquired hemophilia as the initial manifestation of colorectal cancer's recurrence].

Medicina (B Aires) 2021 ;81(2):286-288

Service de Médecine Interne, Diabète et Maladies Métaboliques, Hôpitaux Universitaires de Strasbourg, Francia.

We report the case of an 86-year-old man presenting with a spontaneous hematoma in the left iliac muscle and previous diagnosis of colon cancer in 1998 (stage pT3N0M0) treated with transverse colectomy and considered in complete remission. After a complete study, it was possible to identify the presence of Factor VIII inhibitors antibodies that confirmed the presence of acquired hemophilia. During hospitalization the patient presented a lower gastrointestinal bleeding leading to the diagnosis of recurrence of a previously treated colorectal adenocarcinoma. Read More

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The contribution of individual mental health and socioeconomic status to the evolution of elderly patients with chronic heart failure.

Riv Psichiatr 2021 Jan-Feb;56(2):107-112

County Clinical Emergency Hospital "Pius Brinzeu" Timisoara - Neuroscience Department VIII, Discipline of Psychiatry, University of Medicine and Pharmacy "Victor Babes" Timisoara.

Aim: The purpose of this article is to assess the impact of comorbid depression on the outcome of elderly patients diagnosed with chronic heart failure (CHF).

Methods: We conducted a prospective analysis of the outcomes of 251 patients, hospitalized throughout 2019 for an exacerbation of CHF. The sample was divided into two groups: group A - 153 patients with major depressive disorder (MDD); group B - 98 patients without clinical depression. Read More

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Role of Regulatory Cells in Immune Tolerance Induction in Hemophilia A.

Hemasphere 2021 May 21;5(5):e557. Epub 2021 Apr 21.

Center for Translational Immunology (CTI), University Medical Center Utrecht, University Utrecht, The Netherlands.

The main complication of hemophilia A treatment is the development of neutralizing antibodies (inhibitors) against factor VIII (FVIII). Immune tolerance induction (ITI) is the prescribed treatment for inhibitor eradication, although its working mechanism remains unresolved. To clarify this mechanism, we compared blood samples of hemophilia A patients with and without inhibitors for presence of immunoregulatory cells and markers, including regulatory B-cells (Bregs), regulatory T-cells (Tregs), myeloid-derived suppressor cells (MDSCs), and expression of regulatory markers on T-cells (programmed cell death protein 1 [PD1], inducable T-cell costimulator, cytotoxic T-lymphocyte-associated protein 4 [CTLA4]), by use of flow cytometry. Read More

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FGFR3 overexpression is a useful detection tool for FGFR3 fusions and sequence variations in glioma.

Neurooncol Pract 2021 Apr 20;8(2):209-221. Epub 2020 Nov 20.

Center for Neuro-Oncology, Comprehensive Cancer Center Tuebingen-Stuttgart, University Hospital of Tuebingen, Eberhard Karls University of Tuebingen, Tuebingen, Germany.

Background: Fibroblast growth factor receptor (FGFR) inhibitors are currently used in clinical development. A subset of glioblastomas carries gene fusion of FGFR3 and transforming acidic coiled-coil protein 3. The prevalence of other FGFR3 alterations in glioma is currently unclear. Read More

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Roles of factor Xa beyond coagulation.

Authors:
Wolfram Ruf

J Thromb Thrombolysis 2021 Apr 24. Epub 2021 Apr 24.

Center for Thrombosis and Hemostasis (CTH), Johannes Gutenberg University Medical Center, Langenbeckstr. 1, 55131, Mainz, Germany.

Oral anticoagulant therapy has changed by clinical evidence that coagulation factor Xa (FXa) can be safely and effectively targeted for thromboprophylaxis. Because thrombotic and thrombo-inflammatory diseases are frequently caused by excessive activation of the tissue factor (TF) pathway, activation of FX by the TF-FVIIa complex is of central importance for understanding the roles of FXa in thrombosis and hemostasis and functions beyond blood coagulation. Recent data showed that the nascent product FXa associated with TF-FVIIa not only supports hemostatic cofactor VIII activation, but also broadly influences immune reactions in inflammation, cancer, and autoimmunity. Read More

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Predicting Recurrent Venous Thromboembolism in Patients With Deep-Vein Thrombosis: Development and Internal Validation of a Potential New Prediction Model (Continu-8).

Front Cardiovasc Med 2021 6;8:655226. Epub 2021 Apr 6.

Laboratory of Clinical Thrombosis and Haemostasis, Thrombosis Expertise Center, Cardiovascular Research Institute, Maastricht University Medical Center, Maastricht, Netherlands.

Previous prediction models for recurrent thromboembolism (VTE) are often complicated to apply and have not been implemented widely. To develop and internally validate a potential new prediction model for recurrent VTE that can be used without stopping anticoagulant treatment for D-dimer measurements in patients with provoked and unprovoked DVT. Cohort data of 479 patients treated in a clinical care pathway at Maastricht University Medical Center were used. Read More

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Validation of a perioperative population factor VIII pharmacokinetic model with a large cohort of pediatric hemophilia a patients.

Br J Clin Pharmacol 2021 Apr 22. Epub 2021 Apr 22.

Department of Pediatric Hematology, Erasmus University Medical Center, Sophia Children's Hospital Rotterdam, Rotterdam, the Netherlands.

Aims: Population pharmacokinetic (PK) models are increasingly applied to perform individualized dosing of factor VIII (FVIII) concentrates in haemophilia A patients. To guarantee accurate performance of a population PK model in dose individualization, validation studies are of importance. However, external validation of population PK models requires independent data sets and is, therefore, seldomly performed. Read More

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Breakthrough Bleeding Episodes at Minimum and Improvement in Quality of Life in a Child with Severe Hemophilia A with Inhibitors Treated with Emicizumab: A Case Report from Chile.

Am J Case Rep 2021 Apr 22;22:e929598. Epub 2021 Apr 22.

Department of Hematology, Hospital Roberto del Río, Santiago, Chile.

BACKGROUND People with hemophilia A have shown osteomuscular complications that have a significant impact on their quality of life (QoL) and on health care costs. Patients with hemophilia A with inhibitors living in developing countries such as Chile face a high disease and treatment burden. Emicizumab, a humanized bispecific monoclonal antibody, is associated with improvements in QoL and reduction in the financial impact of the disease related to treatment. Read More

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Acquired hemophilia A associated with Epstein-Barr-virus-associated T/natural killer-cell lymphoproliferative disease: A case report.

Medicine (Baltimore) 2021 Apr;100(16):e25518

Department of Medicine, Division of Gastroenterology and Hematology/Oncology, Asahikawa Medical University.

Introduction: Acquired hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies against factor VIII (FVIII). Hematological malignancies, especially lymphoid malignancies, are known to be underlying causes of AHA; however, thus far, there is no report of AHA associated with Epstein-Barr-virus-associated T/natural killer-cell lymphoproliferative disease (EBV-T/NK-LPD). Here, we present a case of AHA that developed during treatment for EBV-T/NK-LPD. 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 Apr;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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