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RESEARCH ARTICLE

Treatment outcomes, quality of life, and impact of hemophilia on young adults (aged 18–30 years) with hemophilia Michelle Witkop,1* Christine Guelcher,2 Angela Forsyth,3 Sarah Hawk,4 Randall Curtis,5 Laureen Kelley,6 Neil Frick,7 Michelle Rice,7 Gabriela Rosu,8 and David L. Cooper9 The Hemophilia Experiences, Results and Opportunities (HERO) initiative assessed psychosocial issues reported by people with moderate to severe hemophilia and was led by a multidisciplinary international advisory board. This analysis reports data from young adult respondents (aged 18–30 years), including both US and overall global (including US respondents) results, and investigates treatment outcomes, quality of life, and impacts of hemophilia on relationships. More young adults in HERO received prophylaxis than ondemand treatment, although a majority reported not using factor products exactly as prescribed, and 50% of global respondents and 26% of US respondents reported issues with access to factor replacement therapy in the previous 5 years. Many young adults with hemophilia reported comorbidities, including bone/ skeletal arthritis, chronic pain, and viral infections, and nearly half of young adults reported anxiety/ depression. Most reported pain interference with daily activities in the past 4 weeks, although a majority reported participating in lower-risk activities and approximately half in intermediate-risk activities. Most young adults were very or quite satisfied with the support of partners/spouses, family, and friends, although roughly one-third reported that hemophilia affected their ability to develop close relationships with a partner. A majority of young adults reported that hemophilia has had a negative impact on employment, and 62% of global respondents and 78% of US respondents were employed at least part-time. Together these data highlight the psychosocial issues experienced by young adults with hemophilia and suggest that increased focus on these issues may improve comprehensive care during the transition to adulthood. C 2015 Wiley Periodicals, Inc. Am. J. Hematol. 90:S3–S10, 2015. V

䊏 Introduction Psychosocial factors associated with hemophilia have an important impact on patients’ quality of life [1]. The transition from childhood to adulthood, with increased independence in living situations and financial responsibilities, may be particularly challenging for young adult patients with hemophilia (YA-PWH) [2]. After cultivating long-standing relationships and shared experiences with staff at pediatric hemophilia treatment centers (HTCs), the transition to an adult HTC may be difficult. Additionally, living alone or moving to a college/university may be associated with reduced treatment adherence, risky activities (acting out), and attempts to hide the disease from friends, partners, classmates, and coworkers [3,4]. In the United States (US), YA-PWH must secure independent health insurance by the age of 26 to continue to receive treatment [5], and must therefore be declared “disabled” or find employment and decide how to communicate their health status to employers. To increase the understanding of psychological issues affecting people with moderate to severe hemophilia, the Hemophilia Experiences, Results and Opportunities (HERO) initiative investigated the psychological impact of hemophilia. The initiative was led by a multidisciplinary international advisory board that included health care professionals (HCPs), patients, and caregivers. Previous reports have presented the overall HERO quantitative study methodology and demographics of patient and caregiver respondents in the 10 participating countries [6], treatment-related characteristics and access to care [7], the influence of hemophilia on interpersonal relationships [8], and data on pain interference and quality of life (QoL) for adult patients with hemophilia (PWH). While the primary results of adult respondents in HERO demonstrate significant pain interference in activities (89% of 675 adults) and functional impairment, questions have been raised as to whether these data were biased by the pain and disability of older adults who were largely treated on-demand, resulting in greater bleed-related joint damage, and were exposed to plasma-derived products associated with transmission of human immunodeficiency virus (HIV)/hepatitis C virus (HCV). Adoption of primary prophylaxis in the US only began in earnest in the mid2000s; therefore, young adults have likely had variable exposure to primary and secondary prophylaxis during their lives. In terms of 1

Munson Medical Center, Traverse City, Michigan; 2Children’s National Medical Center, Washington, DC; 3BioRx, Mason, Ohio; 4Oklahoma Center for Bleeding Disorders, Oklahoma City, Oklahoma; 5Factor VIII Computing, Berkeley, California; 6LA Kelley Communications, Inc, Georgetown, Massachusetts; 7National Hemophilia Foundation, New York, New York; 8Novo Nordisk Healthcare AG, Zurich, Switzerland; 9Clinical, Medical, and Regulatory Affairs, Novo Nordisk Inc, Plainsboro, New Jersey

*Correspondence to: Michelle Witkop, DNP, FNP-BC; Northern Regional Bleeding Disorders Center at Munson Medical Center, 1105 Sixth Street, Traverse City, MI 49684. E-mail: [email protected] Received for publication: 28 August 2015; Accepted: 13 October 2015 Am. J. Hematol. 90:S3–S10, 2015. Published online: in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/ajh.24220 C 2015 Wiley Periodicals, Inc. V

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American Journal of Hematology, Vol. 90, No. S2, December 2015

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Witkop et al. TABLE I. HERO Adult Respondents by Country and Age Age of PWH respondents Country

No. of respondents

18–30 years

31–40 years

411 years

Median

IQR

% of global YA-PWH

50 50 30 110 50 60 43 41 52 189 675

26 (52%) 15 (30%) 8 (27%) 63 (57%) 16 (32%) 15 (25%) 3 (7%) 11 (27%) 7 (13%) 66 (35%) 230 (34%)

17 (34%) 17 (34%) 8 (27%) 33 (30%) 11 (22%) 11 (18%) 12 (28%) 18 (44%) 8 (15%) 74 (39%) 209 (31%)

7 (14%) 18 (36%) 14 (47%) 14 (13%) 23 (46%) 34 (57%) 28 (65%) 12 (29%) 37 (71%) 49 (26%) 236 (35%)

29 35 38 29 40 43 45 34 47 35 36

23–36 30–51 30–50 25–35 24–50 31–51 38–51 30–43 40–53 28–41 28–45

11.3 6.5 3.5 27.4 7.0 6.5 1.3 4.8 3.0 28.7 100.0

Algeria Argentina Canada China France Germany Italy Spain United Kingdom United States Total (“global”)

HERO, Hemophilia Experiences, Results and Opportunities; IQR, interquartile range; PWH, patients with hemophilia; YA-PWH, young adult patients with hemophilia.

TABLE II. Demographics and Patient Characteristics

Characteristics Age, years Median (interquartile range) Diagnosis, % Hemophilia A Hemophilia B Hemophilia with inhibitors Type of residence, % Large city Suburban area Race, % Caucasian Formal education, % Yes Household income, % 40 years), significant numbers (35%/21%) of young adults reported difficulty in visiting the HTC; the most common reasons for difficulty were accessibility (86%/79%), including distance to travel (72%/57%) and time to travel (58%/29%) (Fig. 2). The HCPs most frequently reported by YA-PWH as being involved in the management of their hemophilia were hematologists and nurses; majorities of YA-PWH were satisfied with care provided

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by all HCP types (Table III). Median (IQR) perceived disease control was rated as 7 (6–8)/8 (7–9) on a 0–10 scale (0 5 least control, 10 5 most control) (Fig. 3A). The majority of YA-PWH (93%/91%) reported being very/somewhat knowledgeable about hemophilia (Fig. 3B), most (70%/62%) were members of a hemophilia society or organization, and many were members of an online (46%/48%) or other support group (45%/35%). When looking toward the future (very pessimistic 5 1, very optimistic 5 7), global and US YA-PWH respondents were generally optimistic (median [IQR] 5 [4–6] and 5 [4–7], respectively) (Fig. 3C).

Pain, arthropathy, and quality of life Despite a relatively young age, many YA-PWH reported comorbidities (Table IV). YA-PWH respondents, compared with those older than 40 years, reported less arthritis (global/US, 40%/41% vs those aged >40 years, 60%/67%), chronic pain (27%/38% vs 50%/57%), and viral comorbidities (21%/20% vs 65%/65%) related to their hemophilia. On EQ-5D-3L assessment, the majority of YA-PWH reported no difficulties with self-care (86%/94%), most reported no difficulties with usual activities (63%/71%), and more than half reported no difficulties with mobility (51%/62%) (Fig. 4A). In contrast, most reported pain/discomfort as moderate (59%/68%) or extreme (11%/5%) (Fig. 4B) on EQ-5D-3L. Anxiety/depression was more commonly reported on EQ-5D-3L as some/moderate (36%/33%) than as extreme American Journal of Hematology, Vol. 90, No. S2, December 2015

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Figure 3. YA-PWH perceived disease control, hemophilia knowledge, and outlook on the next 5 years. YA-PWH, young adult patients with hemophilia.

TABLE III. Access to and Satisfaction with HCPs Involved in Managing Hemophilia Global (n 5 230) Type of HCP Hematologist Hemophilia nurse Social worker Physiotherapist Counselor/psychologist/psychotherapist General practitioner/family doctor Complementary therapist (e.g., acupuncture, massage)

United States (n 5 66)

Involved with management, %

Satisfied with provider,a %

Involved with management, %

Satisfied with provider,a %

88 49 17 29 12 18 6

76 (n 5 202) 82 (n 5 113) 70 (n 5 40) 75 (n 5 67) 78 (n 5 27) 62 (n 5 42) 64 (n 5 14)

83 67 48 26 30 20 8

80 (n 5 55) 86 (n 5 44) 72 (n 5 32) 88 (n 5 17) 85 (n 5 20) 77 (n 5 13) 60 (n 5 5)

HCP, health care professional. a Number and % of those that reported HCP participation.

(6%/8%). In the previous 5 years, 16%/26% of YA-PWH reported seeking psychological treatment; of those seeking treatment, 64%/71% reported that this treatment was related to their hemophilia. On EQ5D-VAS, 42%/53% of YA-PWH reported “good” health-related VAS scores of 80–90–100 (Fig. 4C), compared with 21%/24% for PWH aged older than 40 years. Surprisingly, 86%/89% of YA-PWH reported pain interference with daily activities in the past 4 weeks, with 7%/5% reporting that it was extreme and 13%/5% reporting quite a lot of pain interference (Fig. 5A). YA-PWH were more likely than PWH aged older than 40 years to have pain only with bleeding (YA, 57%/42% vs those aged 40 years, 25%/19%); 12%/14% of YA-PWH reported pain all the time, and 25%/39% reported daily pain and worse with bleeding (Fig. 5B). When asked about specific sports and recreational activities, most YA-PWH reported participating in lower risk (70%/80%) activities, about half in intermediate-risk activities S6


(45%/61%), and some in higher risk activities (17%/27%). As expected, older adult PWH reported participating in more lower risk activities (81%/82%) than intermediate-risk (34%/45%) and higher risk (7%/16%) activities.

Relationships and employment Some YA-PWH (26%/32%) were married or in long-term relationships and few YA-PWH lived alone (15%/20%); most lived with family members (53%/21%), their wife/partner (20%/32%), or others (12%/27%). A significant number of YA-PWH (37%/32%) reported that hemophilia affected their ability to develop close relationships with a partner or prospective partner; reasons for the impact or possible impact are shown in Table V. Although YA-PWH often experienced negative reactions disclosing their hemophilia to friends (36%/ 41%), a majority of YA-PWH (58%/59%) reported that most/all of their friends knew about their hemophilia. doi:10.1002/ajh.24220

RESEARCH ARTICLE

HERO: young adults with hemophilia

TABLE IV. Self-Reported Comorbidities Among Young Adults with Hemophilia Global (n 5 230) Comorbidity Arthritis Chronic pain Viral infectionsa Psychological/psychiatricb Cardiovascular conditionsc Metabolic conditionsd

United States (n 5 66)

Related to hemophilia, %

Unrelated to hemophilia, %

Any, %

Related to hemophilia, %

Unrelated to hemophilia, %

Any, %

40 27 21 26 7 7

2 6 9 26 15 13

42 33 27 43 19 20

41 38 20 30 11 12

0 6 6 35 17 9

41 42 21 53 26 21

a

Includes hepatitis C, hepatitis B, and human immunodeficiency virus/AIDS. Includes stress, anxiety, depression, and insomnia. c Includes angina, heart problems, hypertension, hypotension, and superior vena cava syndrome. d Includes obesity, diabetes, and high cholesterol. b

Figure 4. EQ-5D-3L components and EQ-5D VAS scores in young adults with hemophilia. VAS, visual analog scale.

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Figure 5. Pain interference and association of pain with bleeding episodes.

TABLE V. Reasons for Impact or Potential Impact on Relationships

I am worried about the impact of my hemophilia in future years It is not easy for someone to understand my issues with hemophilia I am worried about being able to support a family in the future I feel different because of my hemophilia I feel less attractive because of my hemophilia I was fearful of their reaction if I told them about my hemophilia I felt unable to do the same things as partners/prospective partners could do Due to lethargy/fatigue

Global (n 5 84) (%)

United States (n 5 21) (%)

63

62

50

62

58

52

55

52

䊏 Discussion

40

38

46

33

37

33

25

19

The initial rationale for exploring YA-PWH respondents in HERO was the hypothesis that potential increased use of secondary and perhaps primary prophylaxis, as well as reduced comorbidities (particularly viral), may result in fewer complications related to hemophilic arthropathy (functional impact and pain) and may decrease the impact of hemophilia on work and relationships. The HERO data demonstrate that despite 50% prophylaxis use and high perceived disease control, YA-PWH reported breakthrough bleeding approximately 1–2 times per month, which occurred with similar frequency in US and global data populations. Compared with older PWH, more YAPWH report participating in intermediate- and higher-risk sports and recreational activities. Additional research is warranted to better understand why prescribed factor regimens are not followed, and the inter-relationships between treatment regimen, adherence/compliance, and intensity of activities to bleeding rate. Another focus of this analysis was to determine if YA-PWH experienced issues with accessing treatment or treatment centers, or if the overall HERO results were driven by responses from older adults. During the period of transition to independence, it is important to note that half of the global respondents and one-fourth of US respondents reported issues obtaining access to factor due to availability or affordability. Additionally, more than one-third of the global respondents and one-fifth of the US respondents reported difficulty in visiting the HTC. YA-PWH were generally satisfied with care provided by all HCP types but indicated that social workers, physical therapists, and genetic counselors were less frequently involved in the management of their hemophilia than hematologists and nurses.

Most YA-PWH were very or quite satisfied with the support of their partners/spouses (95%/95%), family (91%/92%), and friends (86%/86%) (Fig. 6). Most YA-PWH (78%/77%) wanted to have children in the future; only 9%/9% were already parents. Only 41%/45% of YA-PWH received genetic counseling from their HTC; of these, 72%/60% felt that it was helpful. Of those who did not receive genetic counseling, 56%/42% reported that they would find it helpful in the future. Most YA-PWH (62%/78%) were employed at least part-time. Whereas more than half of the US respondents reported office work (57%), this type of work was reported by only 38% of the global respondents. In the US, few YA-PWH received disability benefits (14%), compared with 43% of PWH aged 40 years or older; corresponding data are not uniformly available for non-US respondents. Most YA-PWH (76%/74%) reported that hemophilia has had a negative impact on employment; 47%/39% reported that this was a moderate or very large impact. Equal numbers of YA-PWH reported that most/all of their colleagues at work knew about their hemophilia

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(38%/36%) and that only a few knew (37%/38%); however, a significant number (25%/26%) reported that none of their colleagues knew about them having hemophilia. Most (80%/82%) YA-PWH were very or quite satisfied with the support of colleagues at work and/or at school. The impact of hemophilia on working life is shown in Table VI. Only 30%/36% of YA-PWH received advice from their HTC on employment; of those who did receive advice, 60%/58% of YA-PWH found the advice helpful.


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RESEARCH ARTICLE

HERO: young adults with hemophilia

Figure 6. Satisfaction with support of partners, family, and friends.

TABLE VI. Impact on Working Life

Current treatment allows me to work in most situations I selected my job/training to take into account the needs relating to my hemophilia I believe that having hemophilia has helped me get a job I have had to voluntarily leave a job in the past because of my hemophilia I believe that I have not been hired for a job because of my hemophilia I believe that I have lost a job in the past because of my hemophilia Having hemophilia has had no impact on my choice of job I believe that I have been overlooked for promotion in the past because of my hemophilia I have to restrict the number of hours I work due to my hemophilia I have to work flexible hours due to my hemophilia None of the above

Global (n 5 172) (%)

United States (n 5 49) (%)

33

43

33

37

12

29

20

24

23

20

22

18

19

18

12

10

19

10

17

6

13

4

While YA-PWH are less likely than PWH aged older than 40 years to self-report arthritis, chronic pain, or viral diseases, these comorbidities remain important problems for the younger age group. In particular, pain appears to be a major problem for YA-PWH. Interestingly, while US YA-PWH have greater access to home infusion and factor than their global counterparts, their reported chronic pain is considerably higher (27% of global respondents vs 38% of US respondents). Most YA-PWH reported that pain interfered with recent activities, and many YA-PWH reported daily pain. Bleeding was also fairly common, and hemophilia was certainly one of the issues affecting employment in terms of choice of career/job, communicating with employers and colleagues, and fulfilling responsibilities at work. Taken together, the hemophilia-related complications of bleeding, arthritis, and pain, and their impact on employment suggest a

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broader role for the physical therapist, social worker, and/or career counselor in addressing psychosocial and work-related issues. However, an important limitation of HERO is that respondents were not asked whether they routinely engaged or had access to different members of a comprehensive care team, only whether these professionals were “involved in management.” Respondents may therefore have interpreted this question to reflect only those who manage their factor replacement and underreported care received from other HCPs. Mental health concerns were also substantial in YA-PWH, with many reporting moderate to extreme anxiety or depression. While more than one-third of YA-PWH experienced a negative response to disclosure or impact on relationships, one quarter were in relationships and looked toward having children in the future. YA-PWH reported being very/quite supported by partners/spouses, family, and friends. Despite negative impacts on relationships and work experienced by respondents, it appears that YA-PWH can eventually find caring partners/spouses, strengthen relationships with supportive family members, and seek out relationships with accepting friends and colleagues. A broader role is suggested for the social worker, psychologist, and/or career counselor to address common reports of anxiety/ depression and interpersonal issues. As noted above, this may reflect a limitation in how HERO inquired about comprehensive care team members involved in patient management, but also supports a need for development and integration of education and support programs targeted specifically to YA-PWH. An important focus of these programs should be the ways that this generation of so-called millennials chooses to engage with peers and others, for example, through social media and online peer-support networks. Data from US and global YA-PWH respondents demonstrate consistent challenges in the critical period of transition from living at home with parental support to becoming independent young adults. Responses from these populations appear to be largely similar, although data from US respondents cannot be compared statistically with the overall global data set, and the large representation of US respondents (28.7% compared with 7%–57% from the other 9 countries) may result in an underestimation of any apparent differences between US and non-US respondents. Responses within the US may also be affected by regional biases due to variability in insurance coverage in different states. Interestingly, respondents from China and Algeria were on average younger than respondents from other


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countries, and more than half of the respondents in those countries were YA-PWH (57% and 52%). Home treatment is not as common in those 2 countries, and access to treatment and HTCs was noted in the overall HERO data to be more difficult [7], which may explain the greater issues reported globally with access to treatment and HTCs. Important overall limitations of this analysis are the relatively small number of YA-PWH among the total HERO respondent population, and the potential for respondent bias. Because participants were recruited through national hemophilia organizations (mostly through e-mail and Web pages) and the survey was completed online, the respondent population may be biased toward YA-PWH who are affiliated with hemophilia organizations and who are Interneteducated. Additionally, higher numbers of patients with inhibitors (Global, 14%; US, 21%) were found compared to rates reported by the Centers for Disease Control’s Universal Data Collection (5%) [10], which may be an additional source of bias. Other studies have found the presence of inhibitors to be associated with reduced healthrelated QoL [11,12], and previous reports of HERO data have found associations between inhibitors and greater spontaneous bleeding frequencies [13] and greater impacts of hemophilia on employment [13] and the ability to form close relationships [8].

䊏 Conclusions Young adults represent an important group often caught in the transition. Despite safe treatment products and frequent use of prophylaxis, the results from HERO demonstrate that this group is not free of the impact of hemophilia, including arthritic and viral comorbidities as well as impacts on relationships and employment/careers. Importantly, high rates of pain interference were reported in the YAPWH population. Additional focused discussions and research regarding psychosocial issues are warranted to determine the best approaches to comprehensive patient care in young adults with hemophilia transitioning between pediatric and adult HTCs/providers. Education and support programs also need to be tailored to the different ways that these millennials choose to engage with their peers and the hemophilia community.

䊏 References

1. Cassis FR, Querol F, Forsyth A, et al. Psychosocial aspects of haemophilia: A systematic review of methodologies and findings. Haemophilia 2012; 18:e101–e114. 2. Geerts E, van de Wiel H, Tamminga R. A pilot study on the effects of the transition of paediatric to adult health care in patients with haemophilia and in their parents: Patient and parent worries, parental illness-related distress and health-related Quality of Life. Haemophilia 2008; 14:1007–1013. 3. Beeton K, Neal D, Watson T, Lee CA. Parents of children with haemophilia–A transforming experience. Haemophilia 2007; 13:570–579. 4. Cassis FR. Psychosocial Care for People with Hemophilia. World Federation of Hemophilia 2007. 5. Patient Protection and Affordable Care Act, 42 U.S.C. § 18001 (2010). 6. Forsyth AL, Gregory M, Nugent D, et al. Haemophilia Experiences, Results and Opportunities

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䊏 Acknowledgments Writing assistance was provided by Anna Abt, PhD, ETHOS Health Communications, Newtown, Pennsylvania, with financial assistance from Novo Nordisk Inc, in compliance with international guidelines on Good Publication Practice.

䊏 Disclosures MW has received grant funding from Pfizer, Inc; is on advisory boards with Baxter BioScience, Novo Nordisk, and Pfizer; and is on the speakers bureau at Novo Nordisk. CG is on nursing advisory boards of Biogen Idec, Baxter/BaxAlta, Novo Nordisk, and Griffols; is on the Novo Nordisk Speakers Bureau; and the Solution Sight Speakers Bureau. AF has been a paid consultant and speaker for Novo Nordisk, along with all other major pharma companies; and has received honoraria for speaking from Novo Nordisk, Baxter, and Bayer. SH is on speaker or advisory boards with Baxter, Novo Nordisk, and Pfizer. RC is the project manager for the Hemophilia Utilization Group Studies (HUGS) based in the University of Southern California School of Public Policy, which is funded by unrestricted research grants from Baxter, Bayer, Biogen, CSL Behring, Novo Nordisk, and Pfizer; is on Bayer Speakers Bureau; and has received honoraria from Novo Nordisk, Gilead, Genentech, and the National Hemophilia Foundation. LK gets funding from all the manufacturers of clotting factor (Baxalta, Bayer HealthCare Pharmaceuticals, Biogen Idec, CSL Behring, Novo Nordisk Inc., ASD Healthcare, Octapharma, New England BioLabs, and BioRx). NF has nothing to disclose. MR has nothing to disclose. GR is an employee of Novo Nordisk Inc. DC is an employee of Novo Nordisk Inc.

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www2a.cdc.gov/ncbddd/htcweb/udc_report/udc_ report.asp. 11. Bastani P, Pourmohamadi K, Karimi M. Quality of life in hemophilia complicated by inhibitors. Iran Red Crescent Med J 2012; 14:250–251. 12. Gringeri A, Mantovani LG, Scalone L, et al. Cost of care and quality of life for patients with hemophilia complicated by inhibitors: The COCIS Study Group. Blood 2003; 102:2358– 2363. 13. Forsyth A, Witkop M, Lambing A, et al. Associations of quality of life, pain, and self-reported arthritis with age, employment, bleed rate, and utilization of hemophilia treatment center and health care provider services: Results in adults with hemophilia in the HERO study. Patient Prefer Adherence 9, in press.

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