Appendix E: Literature Review

The Importance of Heath Equity Considerations for Updates, Modifications, and Recommendations to the NHF VWD Toolkit

Marissa C. Melton

NHF HEDI Internship

Dr. Keri Norris

Introduction

NHF is committed to serving people with blood or bleeding disorders and their family members. Von Willebrand disease (VWD) is the most common bleeding disorder and affects up to 1% of the general population (CDC, 2020). The disease occurs in both men and women equally, but women are more likely to notice symptoms because of abnormal bleeding during menstrual periods (CDC, 2021). Unfortunately, even though VWD is the most common inherited bleeding disorder, awareness among health care professionals is low (Sidonio, Zia, & Fallaiz, 2020). It is estimated that 35,000-387,000 patients may have symptomatic, undiagnosed VWD in the United States (Sidonio, Zia, & Fallaiz, 2020). Increased awareness and education of VWD, its symptoms, and recommended treatment would improve the quality of life of individuals living with VWD.

Furthermore, there are several social determinants of health affecting the diagnosis and treatment of VWD. Unconscious bias based on irrelevant characteristics, such as race or gender, can lead to poor evaluation of a patient, further leading to delayed diagnosis and proper treatment (FitzGerald and Hurst, 2017). Specifically, women of color are most affected and can experience providers who do not take their symptoms seriously, leading to delayed treatment and additional complications. Economic stability can affect an individual’s ability to balance the cost of health care with other expenses such as rent/mortgage, food, childcare, transportation, etc. Individuals of lower socioeconomic status struggle to afford these costs and manage their disease. Educational attainment is a barrier than affects how an individual can understand their disease, prescribed treatment plans, and other medical terminology. These examples show how determinants of health can act as barriers to care. Therefore, it is important to discuss these factors and how they affect health education and promotion.

Purpose

The purpose of this literature review is to investigate how different health inequities and barriers affect diagnostics and treatment of individuals with VWD, and how these factors can be addressed to improve awareness of VWD and access to education. This research will help to inform recommendations for the VWD toolkit and the promotional plan. This will ensure that all modifications consider barriers to understanding the content and disseminating the toolkits.

Methods

In order to conduct a comprehensive literature review, a specific protocol was used to find published articles. The search engines used were the Baylor library site, Google Scholar, and PubMed. The first articles found were the official guidelines on the diagnosis and treatment VWD. Due to the specific nature of the research topic, multiple search terms and phrases were used. The search terms included “von Willebrand disease”, “health equity”, “determinants of health”, “inheritable blood disorders”, “digital health equity”, “access to care”, and “women”. These terms were searched together, in different combinations, with the word AND separating them. This was done to ensure that the database used AND as a command to search the terms together. For example, “von Willebrand disease” AND “access to care” was used to locate articles that investigated barriers to care for individuals with VWD. This process was repeated in each data base.

The initial search yielded many results; therefore, inclusion and exclusion criteria were applied. To ensure that the research was current, articles were included if they were published within the past five years. Articles were excluded if they were published outside of the United States, Canada, or Great Britain. Furthermore, articles were excluded if they did not identify barriers or made recommendations for future research or interventions. This refined search resulted in the inclusion of 15 peer reviewed articles in this literature review.

Results

Official 2021 Guidelines on the Diagnosis of VWD

A multidisciplinary panel including patients and representatives from the American Society of Hematology (ASH), the International Society on Thrombosis and Hemostasis (ISTH), the World Federation of Hemophilia (WFH), and NHF created new guidelines for the diagnosis of VWD (James et al., 2021). These guidelines were developed to support patients, clinicians, and other health care professionals in their decisions about VWD diagnosis. The panel reported eleven recommendations to better guide and educate clinicians and patients on diagnostic procedures. Some of the recommendations included redefining the role of bleeding-assessment tools in the assessment of patients suspected of VWD, diagnostic assays and laboratory cutoffs for type 1 and type 2 VWD, how to approach a type 1 VWD patient with normalized levels over time, and the role of genetic testing vs phenotypic assays for types 2B and 2N. It is important to increase awareness of these recommendations so healthcare providers have more knowledge of the disorder and of the process to diagnose someone. Furthermore, these recommendations can be used by family members or friends of an individual with VWD to increase awareness of symptoms they might be experiencing, therefore encouraging them to see a physician and be tested. This will help to increase the number of undiagnosed individuals with the disorder, therefore decreasing adverse health outcomes related to misdiagnosis or a delayed diagnosis.

Official 2021 Guidelines on the Treatment of VWD

The same multidisciplinary panel of patients and representatives from the ASH, ISTH, WFH, and NHF created new guidelines on the treatment of VWD (Connell et al., 2021). These guidelines were created to limit variability in the management of the disorder and to set a standard of care. The panel agreed on twelve recommendations to inform decisions about the management of VWD. Some of the recommendations included prophylaxis for frequent recurrent bleeding, desmopressin trials to determine therapy, use of antiplatelet agents and anticoagulant therapy, target VWF and factor VIII activity levels for major surgery, strategies to reduce bleeding during minor surgery or invasive procedures, management options for heavy menstrual bleeding, management of VWD in the context of anesthesia during labor and delivery, and management in the postpartum setting. These recommendations are extremely important as they provide safety guidelines to limit the chance of bleeding or other adverse health events. It is important to increase awareness of these guidelines to standardize treatments and increase education. This will help to remove some of the burden off the individual with VWD to always be the expert on their disorder. Furthermore, by improving awareness and knowledge on the management of VWD, this will decrease adverse health outcomes and help to improve the quality of life of individuals with the disorder.

Determinants of Health and Identified Barriers

Many of the articles identified and discussed determinants of health that affect access to care and education regarding VWD. FitzGerald & Hurst (2017) reviewed the effects of implicit bias in health care professionals compared to the general population. They found that healthcare professionals exhibit the same levels of implicit bias and that this does influence diagnosis, treatment decisions, and levels of care. They encouraged the use of tests such as the Implicit Association Test to score healthcare professionals on levels of bias and to measure the quality of their treatment.

Arya et al. (2020) investigated healthcare provider perspectives regarding access to care and diagnostic delay among patients with inheritable bleeding disorders. The results found that healthcare providers “identified patients with mild symptomatology, isolated abnormal uterine bleeding, and residence in rural locations as populations at risk for inequitable access to care.” They also identified factors such as socioeconomic status and race influence access to care though not as significant a rural location. The authors encouraged education initiatives to help educate and engage individuals in rural communities.

Arya et al. (2018) investigated inequities in access to care for women with inherited bleeding disorders. Though they found literature was limited, they were able to identify barriers such as demographic, geographic, and systems level factors hindering patients’ access to care. They found that there were greater difficulties surrounding access to treatment for women, including dismissive provider attitudes and ignorance around bleeding disorders in women. They encouraged increasing healthcare provider awareness around existing barriers and with targeted interventions, promote patient self-advocacy. In more recent research, Arya et al. (2021) conducted a qualitative study to investigate barriers for women more closely. They identified four themes surrounding barriers: (1) lack of health-care provider awareness of bleeding disorders, (2) health-care provider dismissal of symptoms, (3) limited access to specialized care and treatment plans, (4) need for sex-education and advocacy. Women with inherited bleeding disorders experience tension in the health care system, feeling unheard, and poorly understood. Therefore, the authors recommended that knowledge and care gaps be addressed with awareness and educational initiatives: patient education on vaginal blood loss, updated medical curricula, clear referral guidelines, and telehealth initiatives for patients residing far from HTCs.

Oladapo et al. (2019) investigated the economic burden associated with major surgeries in patients with VWD compared to patients without VWD who had similar types of surgeries. They found that patients with VWD were significantly more likely to have inpatient admissions, emergency room visits, and outpatient visits. Patients with VWD also incurred significantly higher total health care costs than patients without VWD. This research highlighted the economic burden of medical care for individuals with VWD. This shows how socioeconomic status and economic stability are important determinants of health that affect patient’s access to care and education on their disorder.

Lu et al. (2018) investigated the burden of major bleeding events (MBE) in individuals with VWD. They found that GI bleeding was the most prevalent MBE. Intracranial bleeds were slightly higher in males than females. Patients with MBEs were more likely to have inpatient admissions, emergency room visits, outpatient visits, and will have longer inpatient stays, more frequent inpatient admissions, emergency room visits, and outpatient visits compared to those patients without MBEs. Patients with MBEs incurred significantly higher total healthcare costs than those without MBEs. The readmission rate was 3.1% for any MBE and 2.5% for the same type of MBE. MBEs were associated with additional comorbidities and higher healthcare costs. This research shows the importance of optimal medical therapy to limit chances of adverse health events for patients with VWD. Unfortunately, these adverse health events are more prevalent among the community. These events put a greater economic burden on patients and their families. This economic burden is further compounded by socioeconomic status and stability, again highlighting the effect these determinants have on patient’s access to care.

The final major barrier identified in the research is digital health equity. “Digital health involves digitally enabled tools and environments to augment in-person health care with digital communication, education, and remote care management” (Lyles et al., 2021). In today’s technology filled world, especially with the effects of the COVID-19 pandemic, digital health equity is becoming more important. Lyles et al. discussed how addressing this inequity will cause fundamental changes to health care delivery. The authors identified Black, Hispanic/Latinx, and lower income communities as the most. They encouraged health professionals and organizations to ensure information is available on multiple sources, especially in digital format as it is easier to access and can reach populations in rural communities as well. “These approaches have the potential to address some of the structural challenges for marginalized populations, including lowering access barriers of time and distance and providing tailored communication by language and literacy.” This shows the importance of digital health to increase education and awareness of VWD in rural communities, immunocompromised peoples, the elderly, etc. who do not have the same access to health care providers or information regarding their disorder.

Importance of Health Equity

Many of the articles also discussed the importance of equity in improving health outcomes for the VWD community. Unfortunately, through VWD affects men and women equally, there are major differences in their clinical presentation. Atiq et al. (2021) investigated sex differences in a large cohort of patients with autosomal inherited bleeding disorders (VWD, rare bleeding disorders, and congenital platelet defects). They found that the age of first bleeding was similar between men and women. However, the major difference was diagnostic delay, women were diagnosed much later (11.6+/- 16.4 years) compared to men (7.7 +/- 16.6 years). Women with bleeding disorders are more often referred for bleeding, have a longer diagnosis delay, and often require treatment due to sex-specific bleeding. This shows how a lack of understanding a woman’s clinical presentation of VWD can lead to poor health outcomes. They often suffer longer without diagnosis, which leads to more frequent bleeds or even more severe outcomes like unnecessary hysterectomies. Therefore, heath equity is important to address in this community in order to decrease adverse health outcomes.

Furthermore, Skinner et al. (2020) proposed a treatment model to achieve health equity in the blood disorders community. The treatment model established specific treatment milestones and targeted outcomes linked to level of factor deficiency. Their ultimate goal is functional cure and health equity for this community. The authors identified seven levels to achieve these goals: sustain life, minimal joint impairment, freedom from any spontaneous bleeds, attainment of normal mobility, able to sustain minor trauma without additional intervention, ability to sustain major surgery or trauma, and normal hemostasis. The source suggests that once treatment is not limited by plasma supply for the manufacture of recombinant factors and the success of gene therapy, health equity would be achievable. This sources again highlights the importance of addressing health equity within the community and recommends a unique model that considers the physical milestones of bleeding disorders but also recognizes the limitations to treatments due to cost and resources.

Future Research

Another theme of the reviewed literature were recommendations for future research and interventions to reduce the effects of health inequities on the blood disorders community. Connell et al. (2021) proposed standard definitions to be used in treatment and future research of VWD. These were recommended to improve the ability of researchers to achieve consistent endpoints in future VWD clinical trials. This will ultimately enable improved treatments for affected patients. This is also important as it will decease variability in understanding some of the complexities of the disease. Furthermore, the standard definitions will educate family members and friends of affected individuals as well.

Fogarty, Doherty, & O’Donnell (2020) reported on new advancements that have been made into defining the mechanisms for VWD. They described new laboratory assays that have been developed to enable more precise assessment of specific aspects of VWF activity. They discuss how these advancements will impact clinical diagnosis and routine clinical practice of VWD. It is important to advance treatments and increase understanding the disease because this will improve diagnostic delay, improve treatments, and reduce adverse heath events.

Mannucci (2019) described new therapies and treatment options available for VWD. He described the advantages and limitations to current therapies including desmopressin, FVIII/VWF plasma derived concentrations. He also described newer therapeutic products containing only VWF and how they have been produced through plasma fractionation and recombinant DNA technology. Finally, he described the potential applications of these new replacement therapies in the treatment of VWD and how they could be used in combination with adjunctive therapies. This research is important as it shows that scientists are achieving better understanding of the disease and are improving treatments. This will improve the quality of life of individuals with VWD and their families.

Recommendations and Connections

The purpose of this literature review was to investigate how different health inequities and barriers affect diagnostics and treatment of individuals with VWD, and how these factors can be addressed to improve awareness of VWD and access to education. This research will be used to inform recommendations for the VWD toolkit and the promotional plan. Based on the results, communities of color, women, individuals with less economic stability or socio-economic status, individuals living in rural communities, or persons with lower educational attainment are more negatively affected by the burden of VWD. Therefore, these determinants of health must be considered when making recommendations. To address the determinant of race/ethnicity, the toolkit must have representation of people of color and show the diversity of the VWD community. People of color can also have a distrust of the medical system, therefore by promoting the toolkit to them and increasing their knowledge of their disease, they will be empowered to advocate for themselves. Because women often experience diagnostic delay and worse health outcomes with VWD, it is important to have resources specifically targeted towards women and girls. The resources should target a wide age range, covering topics from puberty to childbirth. Furthermore, by promoting this toolkit to women and providers who care for them, this will increase awareness and education of the disorder at the provider level, hopefully improving diagnostic delay for other young women.

Socioeconomic status and economic stability must be considered in the dissemination of this toolkit. Persons with low-income levels and who lack economic stability are at a disadvantage when trying to care for their disease. This is because they do not have the ability to take time off work to attend doctor’s appointments during the day, or they might have poor insurance or a lack of insurance, meaning the cost of treatment is extremely high. As persons living with VWD have greater economic burden and healthcare costs, the toolkit will be available for free download or will be printed and distributed for free through the chapters and HTC network. Electronic availability of the toolkits also supports individuals living in rural communities who are not located near an HTC or chapter. Having the toolkit available for download or distributed through the chapter/HTC network will ensure equitable distribution for all persons regardless of income level or location.

For persons with lower educational attainment, it is difficult to understand the medical terminology and intricacies of living with VWD. This is even further complicated if English is not an individual’s primary language. Therefore, it is important to consider the reading level of the toolkit. All materials should be written at an eighth grade reading level. Because the aim for the toolkit is to increase education and awareness regarding VWD, a summary of the 2021 guidelines on the diagnosis and treatment are included. This will spread awareness of the new guidelines to improve health outcomes related to managing the disease. Furthermore, the educational materials included in the toolkit will improve patient self-advocacy, helping to empower these individuals. These determinants of health must be considered when updating the toolkit and creating a promotional plan to ensure the information will be equitably understood and disseminated.

Conclusion

The research found in this literature review shows the significant impact determinants of heath have on the VWD community. These determinants cause inequitable distribution of information leading to decreased awareness and education. Therefore, it is important that the VWD toolkit is updated and modified to improve awareness and education while ensuring the toolkit can be disseminated equitably and can be understood by people of all populations.

References

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