Hemophilia Gene Therapy: Another Blessing or Another Curse?

Medical therapies for hemophilia patients over the past 60 years have included several blessings and a curse. The long-sought cure with gene therapy may have finally arrived. Unfortunately, preclinical animal models are now raising concerns for genotoxicity with gene therapy.

Emergent data influences the risk/benefit assessment of hemophilia gene therapy using recombinant adeno-associated virus.

After decades of investigation, gene therapy has received regulatory approval to treat hemophilia. However, since gene therapy investigations were initially conceived, other avenues of treatment have revolutionized the care of hemophilia. Emergent data is showing that gene therapy may not be as beneficial as hoped and more toxic than planned.

Factor activity levels and bleeding scores in pediatric hemophilia carriers enrolled in the ATHNdataset.

Background: Multiple studies have now shown that a significant proportion of hemophilia carriers meet the criteria for having hemophilia and/or report abnormal bleeding. However, to date, investigations of hemophilia carriers have almost exclusively involved women over 18 years of age. Little is known about factor activity levels and bleeding scores in carriers during childhood.

Descriptive analysis of bleeding symptoms in haemophilia carriers enrolled in the ATHNdataset.

Background: Several studies have reported that haemophilia carriers have a bleeding tendency independent of factor activity. However, investigations have been fraught with methodological concerns. The ATHNdataset houses the largest data set of haemophilia carriers in the world.

Normal aPTT in children with mild factor XI deficiency.

It has been suggested that persons with factor XI deficiency can have a normal activated partial thromboplastin time (aPTT). This notion is based on limited data, especially in children. Because of the central role the aPTT plays in diagnostic algorithms for bleeding disorders, it is important to know if a normal aPTT eliminates the need for factor XI activity testing.

Widespread use of fresh frozen plasma in US children's hospitals despite limited evidence demonstrating a beneficial effect.

Objectives: To determine the pattern, prevalence and potential complications of fresh frozen plasma (FFP) use in US pediatric hospitals from 2002-2009.

Study Design: Retrospective cohort study using the Pediatric Health Information System (PHIS) administrative database, which was queried for FFP admissions using diagnostic, procedural, and billing codes. Demographic data, daily use, and procedural codes were used to describe the patient population and pattern of FFP use.

Optimal use of recombinant factor VIIa in the control of bleeding episodes in hemophilic patients.

One of the last remaining clinical hurdles in the treatment of people with hemophilia is the development of inhibitors. Alloantibodies or autoantibodies directed at coagulation factors render the infusion of coagulation factor concentrates ineffective, and alternative means must be used to achieve hemostasis. Recombinant factor VIIa (rFVIIa) was developed to control bleeding episodes in hemophilic patients with inhibitors.

Fresh frozen plasma and recombinant factor VIIa use in neonates.

Background: Little recent data are available describing fresh frozen plasma (FFP) use in neonates. The purpose of this study was to determine the outcomes of FFP transfusions in neonates.

Patients And Methods: A single institution, observational, and retrospective review of each transfusion of FFP given to neonates admitted to a neonatal intensive care unit over a 2-year period.

Thrombotic events in neonates receiving recombinant factor VIIa or fresh frozen plasma.

Background: Numerous recent reports have described the use of recombinant factor VIIa (rFVIIa) in non-hemophilia bleeding situations for achievement of hemostasis. However, its use in clinical situations other than hemophilia patients with inhibitors has been complicated by some reports of thrombotic events. rFVIIa has been used successfully to treat coagulopathic and/or bleeding neonates.

Platelet function disorder in Gardner-Diamond syndrome: a case report and review of the literature.

The Gardner-Diamond syndrome is a disorder characterized by recurrent spontaneous painful bruising in patients with underlying psychosis and neurosis. Despite the presence of other symptoms suggestive of an underlying disorder of primary hemostasis in a large percentage of reported patients, results of testing for von Willebrand disease or platelet function disorders are lacking. The authors describe a case of Gardner-Diamond syndrome in an adolescent girl who had abnormal platelet responses during platelet aggregation studies.

Use of recombinant factor vila to control bleeding in an adolescent male with severe hemophilia A, HIV thrombocytopenia, hepatitis C, and end-stage liver disease.

Few options are available to treat hemorrhaging during the palliative care of patients. Blood products, such as plasma and platelets, are difficult to transfuse in the home or hospice setting. What is needed is a product that can be given in the home setting for effective control of hemorrhaging in patients with various types of coagulopathies.