Heavy menstrual bleeding clinics for adolescents.

Heavy menstrual bleeding (HMB) is a common symptom in adolescence, often leading to significant disruptions in daily life, such as school absences, shame caused by the stigma surrounding menstruation, and symptoms from iron deficiency. Further, HMB may be the first and/or only sign of an underlying bleeding disorder. Navigating the symptoms, effects, and treatments of HMB during adolescence requires a collaborative approach between the patient, caregivers, and healthcare providers.

Trends in dedicated care for females with bleeding disorders within U.S. hemophilia treatment centers.

Graphical representation of increasing percentage of female patients seen at HTCs, percentage of females by diagnosis, number of clinics in existence, and absolute number of female patients seen over a 10-year period (top left then clockwise).

Self-concept and academic achievement in children with chronic kidney disease.

Background: Within the pediatric population, a positive self-concept is associated with better academic achievement. Children with chronic kidney disease (CKD) are at risk for lower quality of life and academic underachievement. Little is known about self-concept among children with CKD and how self-concept influences academic achievement.

Characterization of bleeding symptoms in Ehlers-Danlos syndrome.

Background: Easy bruising is included as a major or minor criterion for the classification of multiple types of Ehlers-Danlos syndrome (EDS). Despite a longstanding recognition of the association between EDS and bleeding, we still lack a definitive understanding of the frequency, severity, and types of bleeding complications in patients with EDS.

Objectives: To evaluate hemorrhagic symptoms using the International Society of Thrombosis and Haemostasis bleeding assessment tool (ISTH-BAT) in a cohort of patients with defined types of EDS.

The intersection of vector biology, gene therapy, and hemophilia.

Gene therapy is at the forefront of the drive to bring the potential of cure to patients with genetic diseases. Multiple mechanisms of effective and efficient gene therapy delivery (eg, lentiviral, adeno-associated) for transgene expression as well as gene editing have been explored to improve vector and construct attributes and achieve therapeutic success. Recent clinical research has focused on recombinant adeno-associated viral (rAAV) vectors as a preferred method owing to their naturally occurring vector biology characteristics, such as serotypes with specific tissue tropisms, facilitated in vivo delivery, and stable physicochemical properties.

BIVV001 Fusion Protein as Factor VIII Replacement Therapy for Hemophilia A.

Background: Factor VIII replacement products have improved the care of patients with hemophilia A, but the short half-life of these products affects the patients' quality of life. The half-life of recombinant factor VIII ranges from 15 to 19 hours because of the von Willebrand factor chaperone effect. BIVV001 (rFVIIIFc-VWF-XTEN) is a novel fusion protein designed to overcome this half-life ceiling and maintain high sustained factor VIII activity levels.

Haemostatic efficacy of single-dose factor administration in neonates with severe haemophilia undergoing circumcision.

Introduction: Perioperative management of children with haemophilia undergoing surgery is a complex and understudied topic. Circumcision is the most common procedure performed in the neonatal period, and guidelines to prevent bleeding complications from circumcision are lacking. Treatment protocols vary widely, and many centres treat patients with factor products for up to two weeks after circumcision.

Laboratory misdiagnosis of von Willebrand disease in post-menarchal females: A multi-center study.

Increased awareness of von Willebrand Disease (VWD) has led to more frequent diagnostic laboratory testing, which insurers often dictate be performed at a facility with off-site laboratory processing, instead of a coagulation facility with onsite processing. Off-site processing is more prone to preanalytical variables causing falsely low levels of von Willebrand Factor (VWF) due to the additional transport required. Our aim was to determine the percentage of discordance between off-site and onsite specimen processing for VWD in this multicenter, retrospective study.

Mental health disorders in haemophilia: Systematic literature review and meta-analysis.

Aim: Despite significant advances in morbidity and mortality outcomes, quality of life for people with haemophilia (PWH) remains compromised. Underrecognized and undertreated mental health disorders decrease quality of life; however, reports are inconsistent regarding the true prevalence of mental health disorders in PWH.

Methods: We conducted a systematic literature search of Ovid MEDLINE, EMBASE, Psychinfo and the Cochrane Library, and hand searched the journal Haemophilia to identify records and subsequently conducted a meta-analysis to determine the prevalence of depression, anxiety and attention deficit hyperactivity disorder (ADHD) in patients with congenital haemophilia.

Pilot trial of semi-automated medical note writing using lexeme hypotheses.

Clinicians write a billion free text notes per year. These notes are typically replete with errors of all types. No established automated method can extract data from this treasure trove.

Successful Management of Blue Rubber Bleb Nevus Syndrome (BRBNS) with Sirolimus.

Blue rubber bleb nevus syndrome (BRBNS) is a rare disease with vascular malformations in several systems of the body, most commonly the skin and gastrointestinal tract. Bleeding from the gastrointestinal (GI) tract is a major complication, which may lead to chronic iron deficiency anemia and the need for frequent blood transfusions due to ongoing gastrointestinal blood loss. In this case report, we describe a now 19-year-old female with BRBNS who required six blood transfusions per year and after starting sirolimus is symptom- and transfusion-free.

Endothelial Cell-Derived Von Willebrand Factor, But Not Platelet-Derived, Promotes Atherosclerosis in Apolipoprotein E-Deficient Mice.

Objective: VWF (von Willebrand factor) is synthesized by endothelial cells and megakaryocytes and is known to contribute to atherosclerosis. In vitro studies suggest that platelet-derived VWF (Plt-VWF) is biochemically and functionally different from endothelial cell-derived VWF (EC-VWF). We determined the role of different pools of VWF in the pathophysiology of atherosclerosis.

Safety and efficacy of a glycoPEGylated rFVIII (turoctocog alpha pegol, N8-GP) in paediatric patients with severe haemophilia A.

Turoctocog alfa pegol (N8-GP, Novo Nordisk, Bagsværd, Denmark), an extended half-life glycoPEGylated recombinant factor VIII (rFVIII), is being developed for prophylaxis and treatment of bleeds in haemophilia A patients. pathfinder™5 is a multinational, open-label, single-arm trial to assess safety, efficacy and pharmacokinetics of N8-GP in paediatric (<12 years), previously treated patients. Boys with severe haemophilia A (<1 % FVIII), no history of inhibitors and previously treated with FVIII products (>50 exposure days [ED] for patients aged 0-5 years [younger cohort]; >150 ED for patients aged 6-11 years [older cohort]) were included.

ADAMTS13 Retards Progression of Diabetic Nephropathy by Inhibiting Intrarenal Thrombosis in Mice.

Objective: ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type I repeats-13) prevents microvascular thrombosis by cleaving prothrombogenic ultralarge von Willebrand factor (VWF) multimers. Clinical studies have found association between reduced ADAMTS13-specific activity, ultralarge VWF multimers, and thrombotic angiopathy in patients with diabetic nephropathy. It remains unknown, however, whether ADAMTS13 deficiency or ultralarge VWF multimers have a causative effect in diabetic nephropathy.

Endothelial Cell-Derived von Willebrand Factor Is the Major Determinant That Mediates von Willebrand Factor-Dependent Acute Ischemic Stroke by Promoting Postischemic Thrombo-Inflammation.

Objective: von Willebrand factor (VWF), which is synthesized in endothelial cells and megakaryocytes, is known to worsen stroke outcome. In vitro studies suggest that platelet-derived VWF (Plt-VWF) is biochemically different from the endothelial cell-derived VWF (EC-VWF). However, little is known about relative contribution of different pools of VWF in stroke.

Shortened Lifespan and Lethal Hemorrhage in a Hemophilia A Mouse Model.

Background: Hemophilia A animal models have helped advance our understanding of factor VIII deficiency. Previously, factor VIII deficient mouse models were reported to have a normal life span without spontaneous bleeds. However, the bleeding frequency and survival in these animals has not been thoroughly evaluated.

Using the laboratory to predict thrombosis in dogs: An achievable goal?

Thrombosis is a major cause of mortality and morbidity in humans and dogs; however, anti-thrombotic drugs carry a risk of bleeding and increase the cost of patient care. The ability to identify individuals at high risk of thrombosis would allow targeting of anti-coagulant therapy at those most likely to derive a net benefit. Significant advances have been made towards predicting thrombotic risk in humans using laboratory tests individually and as part of risk prediction models.

piggyBac-mediated phenotypic correction of factor VIII deficiency.

Hemophilia A, caused by a deficiency in factor VIII (FVIII), is the most severe inherited bleeding disorder. Hemophilia A is an attractive gene therapy candidate because even small increases in FVIII levels will positively alter the phenotype. While several vectors are under investigation, gene addition from an integrated transgene offers the possibility of long term expression.

piggyBac transposase tools for genome engineering.

The transposon piggyBac is being used increasingly for genetic studies. Here, we describe modified versions of piggyBac transposase that have potentially wide-ranging applications, such as reversible transgenesis and modified targeting of insertions. piggyBac is distinguished by its ability to excise precisely, restoring the donor site to its pretransposon state.

A Hyperactive Transposase Promotes Persistent Gene Transfer of a piggyBac DNA Transposon.

Nonviral vector systems are used increasingly in gene targeting and gene transfer applications. The piggyBac transposon represents an alternative integrating vector for in vivo gene transfer. We hypothesized that this system could achieve persistent gene transfer to the liver when administered systemically.

Activation of the epidermal growth factor receptor by respiratory syncytial virus results in increased inflammation and delayed apoptosis.

Respiratory syncytial virus (RSV) preferentially infects lung epithelial cells. Infection by RSV leads to an extended inflammatory response, characterized by the release of interleukin-8 (IL-8). Activation of ERK MAP kinase is required for both RSV-induced inflammation and the extended survival of infected cells.

Respiratory syncytial virus inhibits apoptosis and induces NF-kappa B activity through a phosphatidylinositol 3-kinase-dependent pathway.

Respiratory syncytial virus (RSV) infects airway epithelial cells, resulting in cell death and severe inflammation through the induction of NF-kappaB activity and inflammatory cytokine synthesis. Both NF-kappaB activity and apoptosis regulation have been linked to phosphatidylinositol 3-kinase (PI 3-K) and its downstream effector enzymes, AKT and GSK-3. This study evaluates the role of PI 3-K and its downstream mediators in apoptosis and inflammatory gene induction during RSV infection of airway epithelial cells.