Objective:
The B-HERO-S study evaluated the impact of mild-severe hemophilia B on the lives of affected adults and children. Here we assess the impact of hemophilia B on relationships.
Methods:
US adults with hemophilia B and caregivers of affected children completed separate 1-hour online surveys that included questions regarding impact on interpersonal relationships.
Summary:
Most (88%) of the 299 adults completing the survey had mild-moderate hemophilia B. Of those, 54% were married or in a long-term relationship, and 44% were single. Most adults (87%) reported that hemophilia impacted their ability to form close relationships with partners or prospective partners; 35% were very/quite dissatisfied with the support received from a previous partner. Ninety percent reported that their experiences in a prior relationship, including satisfaction with support from their previous partner, impacted their decision to enter a relationship with their current partner. Nearly all participants (98%) were very/quite satisfied with the support received from their current partner. The top reason for satisfaction was “my partner takes the lead in providing financial security” (45%). Most were very/quite satisfied with the support from family (87%) and friends (96%). Most participants reported a negative reaction or experience as a result of disclosing their hemophilia (friend/colleague/employer, 76%/80%/82%); some reported having felt bullied by peers/colleagues (69%/66%). Majorities reported that past experiences impacted which friends/colleagues they told about their hemophilia, and how or when they disclosed their hemophilia status to these individuals (97%/95%). Seventy-four percent of participants indicated that hemophilia has affected the quality of their sex life; only 54% were extremely/moderately satisfied with their overall sexual relationship. Many reported having had a bleed during sex (40%). Of 150 caregivers of children with mostly mild-moderate hemophilia (74%), 89% were married or in a long-term relationship, and most felt very/quite supported by their partner (98%) and family (87%). Impact on unaffected siblings was more often mixed (49%) than negative (18%). Most felt very/quite satisfied with support of teachers (91%), children at school (80%), and other adults in regular contact (72%). Most caregivers reported negative experiences telling a friend (76%) or having their child tell a friend (69%) about the child’s hemophilia; 43% reported that their child was bullied as a result of having hemophilia.
Conclusion:
While the impact of severe hemophilia on relationships has been reported in HERO and other studies, B-HERO-S suggests that mild-moderate hemophilia B also significantly impacts relationships of affected men/women and boys/girls, especially in terms of disclosure, intimacy, and feeling bullied by peers/colleagues. Opportunities may be explored to more proactively counsel individuals with mild-moderate hemophilia B and families in the setting of comprehensive care to better navigate interpersonal relationships and improve quality of life.
The purpose of this project is to request support for the development of a Virtual Reality Environment (VRE) study program for pediatric patients diagnosed with hemophilia. The VRE program proposed was developed and created for children and includes interactive imagery, character avatars and colorful visual environments. This VRE program will be deployed by the child in a clinical setting and is proposed to help decrease, anxiety and needle phobia during intravenous factor infusions. Outcome measures will include an anxiety scale before and after each infusion, collection of biophysiologic data, pain score and visual analogue evaluation. The expected result of this nursing project is to monitor the use of a VRE in the pediatric population with a reduction of fear, anxiety and pain experienced with intravenous factor infusions.
Dr. Parthasarathy's research will tackle two important biological issues in coagulation - namely how procofactor FVIII converts to the active cofactor form (FVIIIa) and binds to IX and X, and the location of FVIII in generating the active Xase complex. Results from this study will provide molecular and biochemical insights into the role of FVIIIa in regulating hemostasis and further elucidate the interactions between coagulation complexes. Dr. Parthasarathy obtained his Masters in Biotechnology from Jawaharlal Nehru University in New Delhi, India and received his Ph.D. in Biochemistry from the University of Kansas in 2011. He has been a postdoctoral researcher in the lab of Dr. Rodney Camire at The Children's Hospital of Philadelphia since July 2011. This award has been made possible through a generous donation from Hemophilia of Georgia, Inc.
It is unknown if there are differences in attitudes and behaviors between mothers of sons with hemophilia who have a known family history of hemophilia compared to mothers without a known family history. To capture these differences, this study will measure mothers' perceived vulnerability of their sons, protective behaviors toward their sons and reported stress in the mother-son relationship. Sixty mothers will complete the following surveys: Parent Protection Scale, Child Vulnerability Scale and Parenting Stress Index/Short Form. The results of this data will influence clinic social work practice in the comprehensive care model at hemophilia treatment centers.
Dr. von Drygalski's research focuses on better understanding the mechanisms operating the anti-fibrinolytic system and how this process works in patients with hemophilia and specifically with joint bleeding. Accelerated fibrinolysis and clot instability are becoming increasingly recognized as contributing factors to bleeding in hemophilia. One important molecule that prevents fibrinolysis is called TAFI (Thrombin Activatable Fibrinolysis Inhibitor). Dr. von Drygalski will be studying the dual anti-fibrinolytic and anti-inflammatory functions of TAFI in hemophilia arthropathy and develop a therapeutic TAFI-based approach to improving the efficacy of FVIIa based bypassing strategies for acute bleeding and joint protection. Her mentors and collaborators are John H. Griffin, PhD, Laurent O. Mosnier, PhD and Martin Lotz, MD, distinguished researchers at UCSD -The Scripps Research Institute. Dr. von Drygalski received her M.D. from the Universities of Erlangen/Nurnberg and Munich in 1995 and her Pharm.D. from the University of Munich in 1988. She joined the faculty in July 2011 as Assistant Clinical Professor at UCSD and Director of the Adult Hemophilia and Thrombosis Treatment Center, Division of Hematology/Oncology, Department of Medicine. She also has an appointment as Adjunct Assistant Professor at the Scripps Research Institute (TSRI). The funding for this award is made possible thanks to a generous grant from Novo Nordisk.
Per Dr. Fu, the JGP provided her with the opportunity to work on hemophilia, as well as von Willebrand disease. After the completion of her JGP project, Dr. Fu remained in the bleeding disorder field.
Preliminary work done by Dr. Riten Kumar and colleagues has documented that moderate intensity exercise is associated with a significant improvement in multiple coagulation parameters in post-adolescent males with mild-moderate hemophilia A. As a continuation to our previous work, we now hope to compare the impact of moderate intensity exercise to DDAVP on laboratory coagulation parameters in post-adolescent males with mild hemophilia A. We also hope to investigate the impact of sequentially administering these interventions on hemostatic indices. Our over-arching hypothesis is that increase in coagulation parameters (particularly FVIII:C) with moderate intensity aerobic exercise would be non-inferior to DDAVP. We additionally hypothesize that we will appreciate an additive effect of sequentially administering clinical implications for patients with MHA. It may negate the use of DDAVP pre- exercise and could potentially lead to clinicians advising patients to appropriately warm-up (e g running), to raise their FVIII/VWF levels prior to undertaking more rigorous sports. It will also lay the foundation for future studies investigating the interaction between aerobic exercise and hemostasis in subjects with bleeding disorders these interventions. Should our hypothesis be correct, our study would have significant clinical implications for patients with MHA. It may negate the use of DDAVP pre-exercise and could potentially lead to clinicians advising patients to appropriately warm-up to raise their FVIII/VWF levels prior to undertaking more rigorous sports. It will also lay the foundation for future studies investigating the interaction between aerobic exercise and hemostasis in subjects with bleeding disorders.
The project's ultimate goal is to expand nursing knowledge of hemarthrosis/soft-tissue bleeding detection by presenting our HTC's experience with how MSKUS improves accurate diagnosis and guides treatment of bleeding and other pain etiologies. By completing the retrospective data review, we hope that the experience of a large center HTC spanning both adults and pediatrics will be made available. We believe that the current restraints of MSKUS implementation include cost of equipment, operator certification, and quality of interpretation to guide interventions. Therefore, partnering with radiology experts may be helpful for other HTCs around the country when using this modality in the future. Our center's experience will show that collaboration with radiologists for real-time imaging is successful with nursing evaluation and coordination.
Dr. Noh's research will utilize induced pluripotent stem cells (iPSC) and manipulate them in vitro to expand production of megakaryocytes and platelets that express therapeutic proteins, including FVIII. The project will further determine whether this system of autologous platelets which overexpress FVIII can be delivered directly to the site of injury and hemorrhage, thereby circumventing and evading neutralization by alloantibody inhibitors in hemophilia A. Dr. Noh received her Ph.D. in Preventive Pharmacology from Seoul National University in South Korea. She has been a postdoctoral fellow in Dr. Mitchell Weiss' lab at The Children's Hospital of Philadelphia since 2012. Dr. Noh is currently being mentored in this JGP project by Dr. Mortimer Poncz at CHOP.
Introduction:
BAY 81-8973 is Bayer’s new full-length recombinant factor VIII product in development for the treatment of hemophilia A, with no human- or animal-derived raw materials added to the cell culture, purification, or formulation process. The pharmacokinetic (PK) properties of BAY 81-8973 were investigated in 3 studies in previously treated adults, adolescents, and children.
Methods:
For all PK evaluations, a single dose of 50 IU/kg BAY 81-8973 was injected. Serial blood samples were collected over 48 hours in adults and 24 hours in children <12 years of age. PK samples in adolescents and adults were analyzed using one-stage and chromogenic assays. Limited samples were collected in children and were analyzed using only the chromogenic assay. Ethnic subgroups included Chinese, Japanese, and non-Asian patients.
Results:
PK parameters using the chromogenic assay for children (aged <12 years), adolescents (aged 12–17 years), and adults (aged ≥18 years) are shown in Table 1.
Table 1. Pharmacokinetic Parameters Based on the Chromogenic Assay
Conclusions:
Analysis of PK across the different age groups showed that the values for maximum concentration (Cmax) and area under the curve (AUC) for adolescents were within the range of those seen for adults. PK values were slightly lower in children than in adults. There were no significant differences among the ethnic groups studied.
