Research Studies

Objective:

Age is a major risk factor for cardiovascular disease. Comprehensive care and the improved safety of factor replacement therapy and therapeutic approaches, such as prophylaxis, have increased life expectancy for people with hemophilia people with hemophilia (PwH).

PwH may acquire cardiovascular risk factors (such as diabetes, hypertension, hyperlipidemia, obesity and renal disease) as a consequence of advancing age, lifestyle and hemophilia- related conditions, yet little information is available on cardiovascular risk assessment among PWH.

The ADVANCE Working Group, an expert panel of European hemophilia centers supported by an educational grant from Bayer Healthcare, convened to raise awareness of age-related comorbidities among PwH. There are currently no evidence-based guidelines for antithrombotic management in PwH presenting with acute coronary syndrome (ACS). ADVANCE met to perform a review of the current European Society of Cardiology guidelines, and to consider how best they should be adapted for PWH.

Methods:

Structured communication techniques based on a Delphi-like methodology were used to achieve expert consensus on key aspects of clinical management.

Summary:

The main final statements are: a) ACS and myocardial revascularization should be managed promptly by a multidisciplinary team that includes a hemophilia expert; b) Each comprehensive care center for adult PwH should have a link to a cardiology centre with an emergency unit and 24 hour availability of PCI; c) PCI should be performed as soon as possible under adequate clotting factor protection; d) Bare metal stents are preferred to drug eluting stents; e) Anticoagulants should only be used in PwH after replacement therapy; f) Minimum trough levels should not fall below 5-15% in PwH on dual antiplatelet therapy; g) The duration of dual antiplatelet therapy after ACS and PCI should be limited to a minimum; h) PwH receiving antiplatelet therapy should be offered gastric protection; i) The use of GPIIb- IIIa inhibitors is not recommended in PwH other than in exceptional circumstances; j) The use of fibrinolysis may be justified in PwH when primary PCI (within 90 minutes) is not available ideally under adequate clotting factor management.

Conclusion:

It is hoped that the results of this initiative will help to guide optimal management of ACS in PwH.

Objective:

The binding behavior of rVIII-SingleChain to plasma-derived von Willebrand Factor (pdVWF) was assessed in surface plasmon resonance (SPR) studies.

Methods:

The purification of VWF from human plasma–yielded pdVWF free of factor VIII (FVIII). Subsequently, isolated pdVWF was immobilized on a SPR gold chip using monoclonal antibodies (MAbs). Thereafter, the binding behavior of rVIII-SingleChain and full-length rFVIII molecules were studied and binding kinetics were calculated. Regeneration of pd-VWF was performed with calcium chloride, while regeneration of the covalently coupled anti-VWF MAbs was achieved in the presence of an acidic pH.

Summary:

The affinity of CSL Behring’s rVIII-SingleChain to pdVWF was significantly higher than those of commercially available rFVIII full-length molecules. The higher affinity was derived from a higher association rate constant, while the dissociation rate constants were comparable. Intriguingly, the higher affinity had no influence on other functional characteristics of rVIII-SingleChain (eg, the binding to phospholipids, thrombin generation capacity, and FVIII enzymatic activity were comparable to full-length rFVIII). The results obtained from the SPR studies in vitro appear consistent with the observation of improved pharmacokinetic characteristics for rVIII-SingleChain in comparison to full-length rFVIII. After treatment of hemophilia A mice with single doses of rVIII-SingleChain or full-length rFVIII, the systemic availability and mean residence time were found to be increased for rVIII- SingleChain compared to full-length rFVIII. In addition, a decreased clearance rate and an enhanced terminal half-life were observed for rVIII-SingleChain, while in vivo recovery and volume of distribution of rVIII-SingleChain were comparable to full-length rFVIII.

Conclusion:

Overall, it seems conceivable that the higher affinity of CSLB’s rVIII-SingleChain to pdVWF may have a positive effect on its systemic availability by a delayed elimination from plasma.

Objective:

To describe successful buffalo hump removal in 2 patients with Hemophilia and HIV.

Methods/Case Description:

Development of a dorsocervical fat pad, or buffalo hump, occurs in 2-13 % of HIV infected individuals, the etiology is unclear. Two HIV positive patients, one with severe Hemophilia B and the other with severe Hemophilia A had symptomatic buffalo humps for 12 and 7 years respectively. Symptoms included headaches, sleep disturbances, neck stiffness and pain. These symptoms adversely affected activities of daily living. Their HIV disease was well controlled and stable. Both patients had been offered an open excision over liposuction, but the former carries a higher risk of bleeding and pain, as well as poor cosmetic result. The decision was made by a second plastic surgeon to attempt removal through liposuction. For hemostasis they received:

Both patients underwent similar liposuction procedures. 400-600cc of a tumescent solution containing epinephrine and Xylocaine was infiltrated into the subcutaneous tissue in order to minimize bleeding. Traditional liposuction was then performed through 4-5 stab incisions using a variety of cannulas with multiple passes through the fatty tissue attempting to aspirate and break up the fibrous septum connecting the buffalo hump to the cervical fascia. The deeper peri-fascial fat was removed first with later passes aimed at removing the more superficial fatty tissue. Lastly, multiple passes were made in a fan-like distribution to create an even and level contour of the back. Before closing the incisions, the remaining tumescent solution was infiltrated into the remaining cavity to prevent post-operative bleeding and to help with pain control. Both patients tolerated the procedures well with no peri-operative complications and were done in a same day surgery suite, admission was not required.

Results:

Both patients had complete resolution of pre-surgical symptoms and achieved a cosmetically pleasing outcome. Neither patient experienced any recurrence of the fat accumulation 8 and 5 months after the procedures.

Conclusions:

Liposuction is a minimally invasive modality that can be used to successfully remove buffalo humps in people with severe hemophilia, allowing for resolution of pain and improved quality of life.

Objective:

To demonstrate that providing homecare services to bleeding disorder patients with limited English proficiency in a culturally sensitive manner and in their native language can improve quality and outcomes of care.

Methods:

Provider and patient surveys were developed to measure the perceived value of interventions. Respondents were asked to rank dimensions of clarity of translated information, cultural sensitivity, satisfaction, and patient outcomes following homecare interventions on a scale of 1-9. Four patients from different ethnic backgrounds as well as their respective medical providers responded to a survey developed by the authors.

Results:

Our survey and its results, despite small numbers, demonstrate that patients as well as providers see value and improved outcomes when bilingual/bicultural professionals, interpreters and/or qualified translators were provided. Out of a total possible score of 9, an average score of 8.75 to 9 was obtained on the patient surveys. Patient respondents agreed that the information related to their treatment or care was provided in a language that was easy to understand and agreed the homecare service providers accommodated their cultural, religious or spiritual belief practices. Among the surveyed providers, services were ranked at an average of 8.75/9. The providers agreed that the language needs and cultural barriers of their patients were well addressed. It was reported that they “strongly believed” their patients “received accurate instruction on the prescribed treatment plan in a language that was easy for the patient/caregiver to understand” and addressing those needs “exceeded their expectations”.

Conclusion:

According to the Hemophilia Data Set (HDS) there has been a 236% increase in the Hispanic population and a 71% increase for other ethnic populations from 1990 to 2010. Our program has also seen a significant rise in the number of non-English speaking patients on service. This changing demographic landscape necessitates reform in the service delivery in terms of accommodating the needs of cultural diversity and overcoming language barriers. In order to do so, a continuous channel of communication is of high value to monitor and modulate changes in the population. Our survey and its results, demonstrate our success towards those ends, and hopefully will contribute to the continuous quality improvement (CQI) process in the provision of culturally competent care.

Objective:

Who better to understand and help advocate for the bleeding disorders community than those who live it every day? Step Up Reach Out (SURO) was created to help foster the next generation of leaders in the bleeding disorders community.

Method:

SURO is an international leadership program designed to help build tomorrow's leaders in the bleeding disorders community. The program was created by the University of Texas Health Science Center, Gulf States Hemophilia and Thrombophilia Center (UTHS) in 2007 with support from Bayer HealthCare.

SURO brings together young people (18-24 years old) from around the world for learning, personal growth and collaboration. This one-year program consists of two sessions of leadership training, activities focused on developing communications skills, and individual and group projects. During the time between the two sessions, participants are asked to identify an area in their communities for which they would like to step up and define an action plan, putting into practice the skills they have acquired. They continue to learn from and support one another through the SURO Alumni Network.

Summary:

To date, the SURO program has trained nearly 100 individuals from more than 20 countries, ranging from the US to Mexico, India and beyond. SURO alumni have come out of the program ready to put their action plans to the test, developing programming to support their local community needs.

Conclusions:

SURO helps participants build self-esteem, develop concrete thinking abilities and make decisions that will help make them become leaders in their own right.

Objective:

Few online resources are available for teens and young adults living with hemophilia. Frankly.net aspires to serve as a candid, trusted resource on real issues of concern for this age group. Our online forum provides news, tips and information to help young adults with hemophilia live the lives they choose.

Method:

In 2008, an editorial board was established to guide the creation of Frankly.net, an online magazine targeting young men with hemophilia. Board members include experts in the areas of healthcare, social work and advocacy, and two are young men living with hemophilia.

Frankly.net content is controlled exclusively by the editorial board and sponsored by Bayer Healthcare with the goal of casting light on often taboo subjects within the community, such as sexuality, drugs and depression. An editorial calendar is maintained to ensure fresh content is published regularly.

Frankly.net is mobile-optimized and includes rich video content. Users are encouraged to keep up with the latest content by following @FranklyNet on Twitter.

Summary:

Since its inception, the editorial board has guided the creation of more than 80 stories. Articles include topics that resonate with young adults such as travel, entertainment, relationships and sex. Engaging video stories are also available in English and Spanish.

To date, Frankly.net has seen nearly 7,500 visitors from more than 125 countries across the globe, including the US, India, Germany, Canada.

In 2013, Frankly.net underwent a site makeover, re-launching with a new look and feel. Plans to further engage with an international audience are also underway. Korea launched a fully translated site in early 2013 under the guidance of a Korean editorial board. A Latin American version is in development and content from the site has been repurposed and translated in a dozen countries.

Conclusions:

Frankly.net is a unique resource for teenagers and young adults with hemophilia around the world. It continues to push boundaries as a way to help young men navigate the ups and downs of living with hemophilia.

Objectives:

The purpose of this pilot study was to quantify prevalence of food insecurity and determinants among households including children with hemophilia. Food insecurity, the limited or uncertain availability of nutritionally adequate and safe food, negatively affects children’s development and health. Households including people with hemophilia may be at increased risk for food insecurity due to hemophilia-related medical expenses and employment limitations.

Methods:

Food insecurity and health status, as assessed at annual comprehensive visits from May 2012-January 2013 were obtained by chart review. A two-question, validated screening tool was used to assess food insecurity status Descriptive statistics were applied to summarize participant characteristics. This study was approved by the Oregon Health & Science University Institutional Review Board.

Summary:

Data were available for forty-two male participants, aged 0-18 years, 42.9% had mild or moderate hemophilia and 57.1% severe. Prevalence of food insecurity overall was 16.7% (95% CI 5.4-28.0%), similar to national averages; food insecurity was rare among those with mild and moderate disease (5.6%) and concentrated among those with severe disease (25.0%; 95% CI 7.7-42.3%). Additionally, children who were older, taller, heavier, had higher body mass index (BMI) status, or were identified as a minority race or ethnicity were at increased risk for food insecurity (all P>0.05).

Conclusions:

This study provides pilot data showing the need for food insecurity screening and linkage to resources as a routine part of care, and the need for improved understanding of the determinants of food insecurity in this population.

Objective:

When a surgical procedure is required in a patient with hemophilia, continuous infusion of factor (CIF) is a safe and effective alternative to bolus dosing.1-5 However, when cultural values collide with best practices, a patient-centered collaborative care plan is necessary to help ensure a positive outcome while respecting the core values of the patient.

Method:

Our team collaborated with our local Hemophilia Treatment Center (HTC) physicians and nurses to plan CIF for an Amish patient who required a total knee replacement. After interviewing the patient, the care team recognized when the patient transitioned on CIF to the home, we would need to respect the cultural beliefs of the patient without compromising the care.

The HTC physician and nurse ordered continuous infusion of factor for the patient with goal factor levels to remain between 70-100% on post-op days 1-7 and between 50-70% on post- op days 8-14. The home infusion team collaborated with the family and HTC team to finalize the care plan. The patient-centered decision prompted the use of a battery powered ambulatory infusion pump and the use of pre-approved sliding scale factor orders (ACAT protocol) with daily factor levels. Our biggest barrier was in respect to communication with the patient. In our local Amish community, telephones are not accessible. Our brainstorming lead to our COO suggesting we include a battery operated phone that would be attached to the pump and only be used for pump emergencies.

Summary:

The patient was discharged to home post-op day three with recombinant factor VIII running at 2.5 units/kg/hour via a battery operated ambulatory pump. Levels on post-op day four were below 70, prompting the nurse to call on the “pump phone” and return for a visit that night to increase the rate to 2.7 units/kg/hour. The rate remained the same throughout the remainder of the therapy and the levels stayed within the range designated by the physician.

Conclusion:

The patient-centered multidisciplinary care plan allowed for a positive outcome while respecting the patient’s culture.