Objective:
NHF Chapters must develop, support, and sustain influential advocacy programs to protect and enhance access to health care for the bleeding disorders community.
Method:
NHF supports the development of state health care policy advocacy programs with in-kind and financial assistance. NHF’s State-Based Advocacy Coalition (SBAC) program and the standard advocacy expectations our Chapters are the pillars of a robust framework of state advocacy programs. The standard advocacy expectations provide clear expectations and identify best practices for advocacy programming. These include: an advocacy committee of staff and volunteer advocates that meets monthly, multi-year strategic planning, clear engagement with legislative and administrative policymakers, an advocacy annual budget, and more. Chapters are also expected to actively engage their network of Hemophilia Treatment Centers, and all Industry partners.
The SBAC program provides funding and in-kind support from NHF for chapters to either start an advocacy program or grow and maintain an advanced one, using the standard advocacy expectations as a guide. NHF provides extensive in-kind support for SBAC grantees, as well as assisting all other chapters with their specific advocacy needs.
Summary:
Since the inception of the SBAC program NHF has seen participation by and enthusiasm among community members in advocacy events and programming grow. Nearly 500 volunteers participated in NHF’s Washington, DC Days in recent years. Chapter run State Advocacy Days are more prevalent and well-attended. At least 1000 advocates now travel to their state Capitol each year to participate in chapter Advocacy Days. There are 15 grantees participating in the SBAC program covering 20 states. Collectively, NHF has trained more than 5,000 volunteer advocates across the country.
Increasing numbers of volunteer advocates have turned out in state capitols for several years to make their voices heard and influence health care access. In addition, NHF’s investments in public policy resources have allowed us to encourage and support state regulatory advocacy, e.g. with state Medicaid offices. These new efforts have demonstrated tangible results in the form of protecting and enhancing patients’ access to care.
The promotion and support of state chapter advocacy programs by NHF, especially among the SBAC-participating states, has advanced the public policy interests of the bleeding disorders community. Objectively, we’ve seen the increased numbers and enthusiasm of volunteer advocates. Anecdotally, there are many stories of chapters playing a key role in state health care policy,
Conclusion:
Successful state advocacy work has led to improved access to quality healthcare. Start-up and ongoing support from NHF have played a critical role in that success. The continued refinement of our Chapter standard advocacy expectations and in-kind support of NHF policy staff will continue to be key to advancing state advocacy programs uniformly around the country.
Background:
Von Willebrand disease (VWD) is an inherited bleeding disorder caused by a quantitative or qualitative deficiency of the protein, von Willebrand factor (VWF). There is a lack of clear guidance on best practices to inform the care of people with VWD.
Objectives:
Identify and prioritize the main topics of a collaborative guideline development effort.
Methods:
A scoping survey to prioritize topics to be addressed in a collaborative guideline for VWD was distributed to international stakeholders including patients, caregivers, clinicians, and allied healthcare professionals. The distribution strategy was coordinated by the guideline chairs and representatives of the American Society of Hematology (ASH), the International Society on Thrombosis and Haemostasis (ISTH), the National Hemophilia Foundation (NHF), and the World Federation of Hemophilia (WFH). The survey was conducted in English, French, and Spanish. The survey focused on both diagnosis and management of VWD, using 7-point Likert-scale response options and open ended comments. Descriptive analysis of participants and comparative analysis of results by stakeholder subtype (patients/caregivers versus healthcare providers [HCP]), gender, and income setting was performed. Qualitative conventional content data was analyzed utilizing both deductive and inductive coding processes.
Results:
601 participants responded to the survey (49% patients/caregivers, and 51% HCPs). The highest priority topics identified were diagnostic criteria/classification, bleeding assessment tools, treatment options for women, and surgical patients. In contrast, screening for anemia and plasma-derived therapy versus recombinant therapies were rated the lowest priority topics (figures 1 – 2).
Conclusion:
The survey results highlighted areas of importance in the diagnosis and management of VWD across diverse groups of stakeholders and will direct future guideline efforts. The large number responses (601) and discrete comments (9,500) attest to the interest and involvement of the VWD community in this effort.
Specific guidance is lacking for delivery planning in terms of how high a factor level should be achieved for pregnant women with von Willebrand disease (VWD) who, by the third trimester, do not have von Willebrand factor (VWF) (or factor VIII) levels greater than 50-100%. Specifically, guidance is lacking on whether replacement therapy should target a VWF minimum level in the 100–150% range, i.e., a range closer to the 200–250% levels observed in normal pregnancy.
Objectives:
The primary objective is to document the rate of primary postpartum hemorrhage (PPH) and thereby the effectiveness of targeting minimum VWF levels of 100–150% for delivery. The secondary objective is to document further effectiveness outcomes and safety. Patient VWF levels will be maintained at 100-150% for the immediate 72-hour postpartum period, and thereafter maintained at 50-100% target VWF levels through days 5-7 postpartum after normal vaginal delivery or days 7–10 postpartum after caesarean section.
Methods:
This is a prospective, open-label, cohort study of the dosing of Wilate in pregnant patients with VWD to achieve minimum VWF levels of 100–150% for delivery. Outcome parameters will be assessed among patients termed non-correctors and correctors. Patients with a third trimester (gestational week 34–38) VWF level <100% will be enrolled in the non-corrector group. Patients with VWF levels ≥100% at gestational weeks 34–38 will be enrolled in the corrector group. Sample size is based on 65 pregnant VWD non-corrector patients and up to 30 corrector patients. Both correctors and non-correctors will be given tranexamic acid post-partum for 14 days.
Inclusion Criteria: includes VWD patients diagnosed prepartum as type 1 per NHLBI criterion of VWF level <30%, or type 2, or type 3. Exclusion Criteria includes age <18 years, presence of other concurrent disorder of hemostasis, platelet dysfunction, or collagen disorders; presence of liver disease or renal disease, clinical suspicion or diagnosis of preeclampsia or eclampsia, HELLP syndrome, TTP, DIC, or other acquired vasculopathy or coagulopathy, or inability to perform local laboratory monitoring. Primary outcome parameter will be the rate of primary PPH, defined as estimated blood loss ≥1000 mL, or severe PPH defined as estimated blood loss >2000 mL within 24 hours postpartum. Other outcomes are secondary PPH, laboratory measures, and safety. Screening will begin in Q3 2019 and end in Q2 2023, with recruitment ending 6 months before (i.e., Q4 2022).
Summary:
This planned study aims to determine in VWD if VWF levels postpartum should be attained at levels closer to levels achieved physiologically in a normal pregnancy.
Conclusions:
Results from this study will hopefully lead to reduction of the relatively high rate of PPH in VWD women with levels <50-100% in the third trimester.
Background:
Recombinant adeno-associated viruses (rAAV) are replication-deficient, non-integrating viruses commonly used as vectors for gene therapies currently in clinical development. Systemic administration of gene therapy raises the possibility of vertical germline transmission of the vector DNA.
Aim:
Here, we investigated the possibility of germline transmission following IV administration of an AAV serotype 5 vector designed for the liver-directed expression of human Factor IX which is being studied in clinical trials for hemophilia B.
Methods:
Since hemophilia B predominantly occurs in male patients, paternal germline transmission was investigated in mice in a GLP compliant study, according to current gene therapy guidelines (EMEA/273974/2005). Male C57Bl/6 mice (n=15) each received a single intravenous infusion of 2x1014 gc/kg AAV5-hFIX and were mated 6 days later with untreated female mice (n=30). On day 20 post-treatment, males were sacrificed and the seminal vesicle, epididymis, testes and a sperm sample were collected. Successfully mated females were necropsied on day 17 of gestation and the uterus, placenta and fetuses collected for each female. Each fetus was examined for viability and externally visible abnormalities. All samples were analyzed for vector DNA by QPCR.
Results:
No effect of treatment was observed on male mating performance, fertility indices, maternal body weight, food consumption, pregnancy performance, external fetal abnormalities, or fetal weights. Vector DNA levels of up to 2x106 gc/μg gDNA were detected in male reproductive tissues (epididymis, seminal vesicle, sperm, and testes), but not in female uterus, placenta and offspring. Although vector DNA was detected in the reproductive tissues of males, there was no evidence of transmission of vector DNA to female reproductive tissues or to the fetuses.
Conclusion:
The risk of paternal germline transmission following AAV5-based vector administration is therefore considered to be low.
The hemophilia and thrombosis centers in Tucson and Phoenix would like to join efforts to make a meaningful contribution to our understanding of the mental health profile of our pediatric population. This knowledge could contribute to a more tailored approach when designing clinics and programming, and, by identifying mental health issues, inform the development of targeted interventions. We hope to look at the prevalence of depression and anxiety in children with bleeding disorders including hemophilia, von Willebrand disease, and other congenital coagulopathies. We expect that the existence of a chronic health condition could affect a child's psychological development. We're also aware of the critical impact of family culture so our survey will include data on the mental health of the participants’ primary caretakers as well as other significant socioeconomic markers.
Objectives:
This study has a primary objective to determine the efficacy of VWF/FVIIII concentrate (Wilate) in the prophylactic treatment of previously treated patients with type 3, type 2 (except 2N), or severe type 1 VWD.
Secondary objectives of this study will be to collect data to 1) Assess the VWF:Ac and VWF:Ag incremental IVR of VWF/FVIIII concentrate over time, 2) Assess the safety and tolerability of VWF/FVIIII concentrate in this indication.
Also the study will examine, the efficacy of VWF/FVIIII concentrate in the treatment of breakthrough bleeding episodes (BEs), and in surgical prophylaxis, as well as the quality of life (QoL) during prophylaxis with VWF/FVIIII concentrate.
Methods:
The study is planned to enrol 28 PTPs aged ≥6 years and with VWD type 1, 2A, 2B, 2M, or 3. Eligible patients must be receiving on-demand treatment with a VWF-containing product, with at least 1, and an average of ≥2, documented spontaneous BEs per month in the preceding 6 months requiring treatment with a VWF-containing product. This will be assessed as part of a run in observational study to collect bleeding rate prior to the start of prophylaxis.
From the beginning of the study, patients will receive prophylactic treatment with VWF/FVIIII concentrate for 12 months and record all BEs in a patient diary. Based on these data, the frequency of BEs and the annualized bleeding rate (ABR) under prophylactic treatment will be calculated.
Treatment efficacy of BEs will be assessed by the patient (together with the investigator in case of on-site treatment) using a 4-point scale (excellent, good, moderate, none)
In case patients undergo surgeries, efficacy of VWF/FVIIII concentrate will be assessed at the end of surgery by the surgeon and at the end of the postoperative period by the haematologist. In both cases, predefined assessment criteria will be used. In addition, an overall assessment of efficacy will be made at the end of the postoperative period by the investigator.
Summary/conclusions:
Prophylactic treatment in other congenital bleeding disorders is widely accepted as the standard of care to prevent bleeding and preserve quality of life in patients. This form of treatment in VWD is not well characterized prospectively as yet. This study will provide data on the efficacy of prophylactic treatment in reducing the rate of bleeding and on the impact of prophylaxis on the quality of life in VWD patients.
Objective:
To investigate how bleeding disorder characteristics influence patient perceived challenges and management strategies.
Methods:
This is a mixed-method, retrospective, cross-sectional continuation of a pilot study identifying themes of self-perceived challenges and management strategies for persons with bleeding disorders. Sixty-one participants with a bleeding disorder (BD), either hemophilia (PWH) or Von Willebrand disease (PWVWD), were asked what their most significant challenge was in managing their BD and how they managed that challenge. Data were collected from March, 2017 through December, 2018, coded for themes and uploaded to NVivo. Similar themes were grouped for analysis. Subject-level data was extracted from the electronic medical record including demographics, disease type, severity and presence of joint disease (JD). Pain interference was determined from participant response to the Brief Pain Inventory (BPI).
Results:
Conclusions:
Gaining insight to patient-perceived challenges and management strategies is important to be able to tailor an effective treatment approach that is individualized and meets the changing needs of PWBD across circumstance and life-course.
Dr. Satish Nandakumar is currently a postdoctoral fellow in the laboratory of Dr. Vijay Sankaran at the Boston Children's Hospital. Previously, he did his graduate work at the St. Jude's Children's Research Hospital in Memphis, Tennessee. In his JGP Fellowship project, Dr. Nandakumar aims to develop a novel gene therapy approach for hemophilia that involves activation of the endogenous factor VIII or IX genes within hematopoietic stem cells by taking advantage of the CRISPR/Cas9 gene activation system. This work has the potential to benefit patients with mild hemophilia mutations.
Helping teens with bleeding disorders prepare to manage their care as they transition to adulthood is a national priority for US Hemophilia Treatment Centers (HTC). The National HTC Patient Satisfaction Surveys (PSS) reveal high satisfaction with HTC teen transition services. Yet how satisfaction differs comparing HTCs that primarily care for children to HTCs that care for patients throughout the lifespan is unknown.
Objective:
To assess variation in patient satisfaction with US HTC teen transition services by HTC type.
Methods:
The US HTC Network conducted nationally uniform patient satisfaction surveys in 2015 and 2018 on care received, respectively, in 2014 and 2017. A Regional workgroup devised, piloted, and finalized an electronic, two-page survey for self-administration at clinic, or at home, in English or Spanish. Participation was voluntary. Respondents were anonymous but identified their HTC. Parents completed surveys for children under age 18. The PSS included two teen transition questions for respondents age 12-17 to complete. HTC type was categorized as ‘pediatric’ if >80% of responses were from patients/caregivers of individuals under age 18, and ‘adult’ if >80% were from patients over age 24. All other HTCs were categorized as ‘lifespan’. For both years, approximately 26% of HTCs were classified as pediatric, 52% as life-span, and 22% as adult.
Results:
Over 700 teens age 12-17 (or their parents/guardians) from an average of 130 HTCs (94.0%) from all US regions participated in 2015 and 2018. Approximately 96.5% of teens at pediatric HTCs (96.4% - 96.5%) and 96.2% at lifespan HTCs (95.9% - 96.5%) reported being ‘always’ or ‘usually’ (A/U) satisfied with HTC services overall. On average, 90.4% of teens at pediatric HTCs (90.1% - 90.7%) and 91.0% at lifespan HTCs (90.3%–91.6%) reported being A/U satisfied with how HTC clinic staff talked about how to care for the bleeding disorder as they became an adult. Similarly, 92.5% (92.0%– 92.9%) of teens at pediatric HTCs and 92.5% (92.3%-92.7%) reported being A/U satisfied with how the HTC clinic staff encouraged them to become more independent in managing their bleeding disorder.
Conclusions:
HTC patients age 12-17 years consistently report very high levels of satisfaction with HTC teen transition services, regardless if the HTC primarily cares for patients up to age 17, or throughout the life-span. This suggests teens receive support and tools to successfully transition to adult care across the US HTC Network. A national uniform HTC Patient Satisfaction Survey provides vital information, is feasible to conduct using a regional structure, and well received nationwide.
