“Adherence Issues in Hemophilia: Strategies for Improving Quality of Life and Patient-Reported Outcomes”

"Adherence Issues in Hemophilia: Strategies for Improving Quality of Life and Patient-Reported Outcomes"
Patrick F. Fogarty, MD, and Susan Karp, RN, MS
November 29, 2012

Eric is a 15-year-old male with moderate hemophilia A and no inhibitor. He has been on a 3x weekly prophylaxis regimen of factor VIII concentrate for most of his life. However, since starting high school, he has become less disciplined about infusing, claiming that the strict regimen interferes with his extracurricular activities and time spent with friends. According to Eric's parents, he follows his treatment plan only sporadically and as a result has experienced an increase in bleeding episodes.

If aspects of the above scenario seem familiar to you, you are not alone among hemophilia-treating clinicians. The very nature of a chronic illness can permanently impact the patient, his family, and his future life course, as continuous adaptation to the illness is required.1 There may be an unpredictable disease course, reduced physical performance/ability, change in appearance, prolonged dependence on medical personnel, or changes in life prospects.1 Such factors may lead to social restrictions, feelings of isolation, emotional turmoil and disruption, and compared to acute illness, a life-long commitment to treatment.1, 2, 3

While adherence to any long-term regimen is a challenge, for patients with hemophilia, who may require management beginning at birth and throughout all life stages, adherence may be particularly challenging.4 Nevertheless, it may have a possibly greater impact on a patient's health than any one specific treatment.5 There are undeniable benefits that adherence to treatment may confer over the lifetime of the patient. It has been demonstrated that bleed prevention correlates with reduced emergency department visits, hospital admissions, and clinic visits, as well as increased physical activity and academic improvements.6, 7 Moreover, as demonstrated by Aledort and colleagues, reduction of joint bleeds is the most critical factor for a good orthopedic outcome for children and young adults (younger than 25 years) with severe disease.8

Conversely, nonadherence to treatment can have negative repercussions for patients, including limited treatment efficacy and suboptimal bleed prevention.7  Irreversible joint disease may be triggered by only 1 or 2 inadequately treated or controlled bleeds.3 There also may be increased healthcare costs due to the bleeding complications arising from poor adherence to a therapeutic regimen, with haphazard treatment equating to wasted resources and worsening long-term outcome.6

"Patients need to be supported, not blamed." —World Health Organization.9

While there is no accepted definition of adherence, it traditionally has been viewed as the extent to which a person's behavior coincides with medical or health advice.1, 10  This narrow perception focuses on patient-related factors and views nonadherence as the fault of the patient.9

However, within the past decade, there has been a shift in the way adherence is regarded. It is now considered "active, intentional and responsible process of care in which the individual works to maintain his or her health in close collaboration with healthcare personnel," 1  a perception that places the onus of responsibility for adherence on the patient and healthcare provider alike. This new view introduces 2 key questions for clinicians: What are the barriers to adherence for hemophilia patients? What strategies can healthcare providers employ to assist their patients in adhering to treatment to improve quality of life (QoL) and outcomes? Possible answers to these questions are explored by way of case examples, expert commentary, and clinical trial data.

José R. is a 19-year-old male with severe hemophilia A and no inhibitor. He has joint contractures and was previously advised to use prophylaxis for joint bleeding episodes occurring once every 1 to 2 weeks, primarily in his right knee and left ankle. The patient lives at home with his extended family. There are limited financial resources, and the patient has admitted in the past that it is a struggle to obtain the bare essentials and still pay rent. English is not spoken at home. José has lived in the United States for 6 years and recently received US citizenship. The nearest hemophilia treatment center (HTC) is 50 miles from his home, and because he must rely on public transportation, his visits to the center are infrequent. He has not been dispensed factor in 6 months and has a history of yo-yoing between prophylaxis and on-demand treatment. Additionally, there has been no follow-up with requested tests, specifically an MRI and an X-ray. He has cited health insurance issues as a reason. He had a psychosocial evaluation 1 year ago, at which time he expressed fear and frustration regarding the bleeding disorder and anxiety about his future. There have been no intervening psychosocial evaluations.

Expert Q&A with Patrick F. Fogarty, MD,
and Susan Karp, RN, MS


Current research indicates that pediatric patients have better rates of adherence than do adolescent and adult patients. 5, 11  According to the 2003 Haemophilia A Practice Patterns Survey, adherence is highest among infants and children and lowest among adolescents and young adults (Table 1).11

Low rates of adherence among the adolescent and young adult cohort have been examined by other investigators as well. Hacker and colleagues conducted a telephone survey on prophylaxis adherence among 38 participating subjects (or their parents) with hemophilia A or B.4  Issues covered in the survey included decision to initiate prophylaxis; adherence self-assessment; challenges, barriers, and facilitators of prophylaxis; and perceived value of therapy. Investigators' criteria for self-rated adherence were based on percentage of prescribed infusions administered, with excellent and good adherence requiring 76% to 100% and 51% to 75% of prescribed infusions, respectively. Based on these criteria, the study team found that only a little more than half the patients aged 1 to 18 years had self-reported rates of adherence described as excellent.

Lack of Knowledge

In 1999, reporting on the perceptions of transplant clinicians regarding patient compliance, Hathaway and colleagues noted that poor knowledge was a determinant of noncompliance.12  Several years later, Lindvall et al noted a similar association in the hemophilia population.13  He and his team conducted a prospective multicenter study to determine adherence to prophylactic treatment among 108 hemophilia patients aged 13 to 25 years. Investigators found that an overwhelming majority of patients possessed a high degree of self-knowledge about disease type and severity (96% and 99%, respectively), with a correspondingly high percentage of patients (68%) treating bleeds immediately. However, it was also found that 41% of the study population did not follow primary prophylaxis as prescribed. Investigators positively correlated adherence with a high degree of knowledge about hemophilia.

A follow-up study by Lindvall and investigators in an older patient cohort (>25 years) showed a similar correlation between self-knowledge and adherence.2  Among 413 survey respondents, 96% were aware of hemophilia type, and 93% were aware of disease severity. Correspondingly, only 15 patients interrupted treatment for less than 1 month, and 25 patients on prophylaxis for a median of 16 years decided on their own to stop completely.

Adolescence and Transitioning

The transition to adulthood can be especially challenging for adolescents with disabilities.14  This is often the time when hemophilia patients move toward greater independence and begin to self-infuse, assuming responsibility for much of their care.10  A lack of adolescent-focused education can foster nonadherence to treatment at this time, with a shift in focus from parent (the object of much of the early education, beginning at time of diagnosis) to child. Providers need to educate patients in a developmentally appropriate fashion through all stages of the life cycle and especially through adolescence, bearing in mind the issues confronted by adolescents and the potential impact of these issues on adherence.14  During adolescence, personal identities are developed and relationships outside the family are built.14  There is a tendency to move away from authority figures, including parents, and focus on self.15  Although adolescents begin to engage in abstract reasoning and problem solving, they are still oriented in the present and give little thought to the long-term consequences of their actions.15

The Lindvall studies point to the importance of education as a promoter of adherence. In Lindvall's investigations, surveyed patients believed that HTCs provided the best education/information about hemophilia, leading the study team to conclude that given the value placed on education, HTC staff should provide patients with an opportunity to understand the nature of the disease, risks of complications, benefits of treatment, and importance of self-care.2, 13  Participants viewed the HTC nurse, in particular, as essential to their education about the disease. As such, nurses should meet with patients to discuss hemophilia type, severity, benefits of regular treatment, breakthrough bleeds, physical activities, and work and/or school issues.2

Sean M. is a 16-year-old male with severe hemophilia A and an inhibitor. He has been adherent to a prophylaxis regimen using rFVIIa for the past several years. His disease course has been uneventful, with infrequent bleeding episodes controlled by his treatment. He is in his final 2 years of high school and looks forward to attending college out of state.

Expert Q&A with Patrick F. Fogarty, MD,
and Susan Karp, RN, MS

Supplemental Information
Listen to Blood CME Center faculty member Roshni Kulkarni, MD, address the management of lifestyle and QoL challenges for patients who are "Transitioning From Pediatric to Adult Hemophilia Care"

For additional information on the transition process, refer to the National Hemophilia Foundation's "Guidelines for Growing: An Action Plan for Teens With Bleeding Disorders," part of a series that focuses on social and developmental milestones from birth through adolescence.

Although a relatively large body of research into adherence has been generated within the past 10+ years by different investigators working out of different countries, using different methods, all have arrived at similar conclusions regarding barriers to adherence.4, 5, 14, 15  The major barriers have been found to include a lack of understanding of the disease, the time-consuming nature of prophylaxis, balancing prophylaxis with other social/family needs, venous access, and cost. Another barrier includes patient perception about treatment, with a number of patients feeling that treatment is not necessary or beneficial.4, 5  According to the World Health Organization (WHO), adherence is usually compromised by more than one barrier.9  Clinicians should address each individually. Although some barriers, such as socioeconomic status and family dynamics (Table 2), are unmodifiable, such barriers should be used to define subpopulations requiring more education and follow-up.6

Timothy K. is a 23-year-old male with moderate hemophilia and no inhibitor. He has a mild cognitive impairment and challenging personal and family issues. Timothy lives in a boarding house located near his HTC. Although he has been on prophylaxis for most of his life, he has difficulty remembering to order his replacement therapy. This became an issue when he began living independently. Recently, he had his first visit with the adult care team. His transition had been delayed due to problems associated with the cognitive impairment.

Expert Q&A with Patrick F. Fogarty, MD,
and Susan Karp, RN, MS

Due to a lack of consistent and validated measures of adherence, assessment is not standardized: 6, 7  Some clinicians do not adequately assess adherence, while others do not assess adherence at all (12.5% of physicians and 17.6% of nurses, according to data generated by Chan et al).5

Extant measures of assessment include pharmacy records, number of joint bleeds, functional assessments, and self-reports, the most common measure.6, 16  The Veritas-PRO is one such type of report (see Appendix A). A self-observer—reported questionnaire, it comprises 24 items divided into six 4-item subscales: Time, Dose, Plan, Remember, Skip, Communicate.7  Although one recently conducted study found it to be a reliable and valid measure of adherence, it is not widely used in clinical practice.7, 16

Infusion logs/diaries are a more common self-reporting measure by which to assess hemophilia patients on home treatment.3, 6  Keeping up with technology, many logs are available in an electronic format, such as the one provided by Hemophilia of Georgia HTC (see Appendix B).17   Patients have the opportunity to download a treatment calendar, enabling them to electronically monitor the amount of factor they infuse. Additionally, they can record whether treatments are preventive or for arresting a bleeding episode.18  Hemolog represents another innovation in self-reporting. Available as an app for the iPhone, iPod Touch, and iPad, it enables patients to quickly log factor infusions and record the anatomic location of each bleed (see Appendix C).18, 19  Taking infusion diaries one step further, ATHNadvoy, a Web-based reporting system offered by the American Thrombosis and Hemostasis Network (ATHN), not only allows patient infusion and bleed logs to be imported electronically, it manages these logs side by side with other clinical information20  (see Appendix D). HTCs are able to use the patient-reported information to customize patient care plans.20

Supplemental Information

According to WHO, there is no one intervention to improve adherence.9  A multifaceted approach is necessary, with interventions targeted to the particular demands of the illness.9, 16  For instance, if education is required, it should be tailored to the literacy of the patient. If patients have difficulty ordering factor concentrate (as Timothy does), frequent HTC follow-ups should be requested, taking into account variables such as distance from HTC.16  In this regard, the HTC staff may be able to assist patients by providing resources such as gas cards, meal cards, and housing subsidies.

Other strategies to improve adherence have been identified. The quality of the interaction between the HTC staff and the patient is an important factor in facilitating compliance to a treatment plan.1  Clinicians and support staff should listen to the needs of patients, be empathetic, and convey a sense of care. 1, 15

Other ways to promote adherence include involving teens in transition planning, with both outgoing pediatric and incoming adult providers in attendance at transition clinics.14, 15, 21  Additionally, treatments should be tailored to the lifestyle of the patient. 1, 21  This should entail modifying a prophylaxis schedule with a graduated course.6  Patient involvement in care should be encouraged through frequent visits to the healthcare provider, if practical.21  Regular HTC visits serve an additional purpose of ensuring continued ability on the part of the clinician to write prescriptions for factor.

Clinicians should also encourage the support of family and friends (including pets). Fostering an interaction between patients and others may quell any feelings of isolation the patient may experience. Promoting peer involvement (eg, hemophilia summer camp) is another way for HTC staff to assist patients with any feelings of isolation or alienation. Additionally, in the later pediatric years, clinicians should interview the patient alone, to accustom him to HTC visits without parental accompaniment. A drafted contract between the patient and care provider, with a stated desired outcome, can also potentially improve adherence.15  Surveyed patients and caregivers believe that an understanding of the benefits of prophylaxis, motivation from knowing that prophylaxis reduces the stress of hemophilia, and support from multiple sources, including the HTC, family, and friends, are additional ways to improve adherence.

Research continues to shed light on the determinants of adherence, providing clinicians with a greater understanding of the barriers and means to ensure compliance among patients. Knowledge is a key component of adherence. Although the chronic nature of hemophilia can impinge on a patient's life, an enlightened HTC staff can support the perception that treatment is a normal part of life and a route to improved clinical outcome.


  2. 1. Kyngä H. Compliance of adolescents with chronic disease. J Clin Nurs.
  3. 2. Lindvall K, Colstrup L, Loogna K, Wollter I-M, Grönhaug S. Knowledge of disease and adherence in adult patients with haemophilia Haemophilia. 2010;16:592-596.
  4. 3. Du Treil S, Rice J, Leissinger CA. Quantifying adherence to treatment and its relationship to quality of life in a well-characterized haemophilia population. Haemophilia 2007;13:493-501.
  5. 4. Hacker MR, Geraghty S, Manco-Johnson M. Barriers to compliance with prophylaxis therapy in haemophilia. Haemophilia 2001;7:392-396.
  6. 5. Chan AKC, Decker K, Warner M. Adherence with haemophilia treatments: a survey of haemophilia healthcare professionals in Canada [letters]. Haemophilia 2011;17:815-829.
  7. 6. Thornburg CD. Prophylactic factor infusions for patients with hemophilia: challenges with treatment adherence. J Coag Disord. 2009:1-6.
  8. 7. Duncan N, Kronenberger W, Roberson C, Shapiro A. VERITAS-Pro: a new measure of adherence to prophylactic regimens in haemophilia Haemophilia 2010;16:247-255.
  9. 8. Aledort LM, Haschmeyer RH, Pettersson H; Orthopaedic Outcome Study Group. A longitudinal study of orthopaedic outcomes for severe factor-VIII-deficient haemophiliacs. J Intern Med. 1994;236:391-399.
  10. 9. World Health Organization. Take-home messages. In: Adherence to Long-term Therapies—Evidence for Action. http://apps.who.int/medicinedocs/en/d/Js4883e/5.html. Accessed March 22, 2012.
  11. 10. Fischer K, Valentino L, Ljungs R, Blanchette V. Prophylaxis for severe haemophilia: clinical challenges in the absence as well as in the presence of inhibitors. Haemophilia 2008;14(suppl 3):196-201.
  12. 11. Geraghty S, Dunkley T, Harrington C, Lindvall K, Maahs J, Sek J. Practice patterns in haemophilia A therapy—global progress towards optimal care. Haemophilia 2006;12:75-81.
  13. 12. Laederach-Hofmann K, Bunzel B. Noncompliance in organ transplant recipients: a literature review. Gen Hosp Psychiatry. 2000;22:412-424.
  14. 13. Lindvall K, Colstrup L, Wollter I-M, et al. Compliance with treatment and understanding of own disease in patients with severe and moderate haemophilia. Haemophilia 2006;12:47-51.
  15. 14. Breakey VR, Blanchette VS, Bolton-Maggs PHB. Towards comprehensive care in transition for young people with haemophilia. Haemophilia 2010;16:848-857.
  16. 15. Muscari ME. Rebels with a cause: when adolescents won't follow medical advice. Am J Nurs. 1998;98:26-30.
  17. 16. Thornburg CD, Carpenter S, Zappa S, Munn J, Leissinger C. Current prescription of prophylactic factor infusions and perceived adherence for children and adolescents with haemophilia: a survey of haemophilia healthcare professionals in the United States. Haemophilia 2012:18:568-574.
  18. 17. Hemophilia of Georgia. Treatment Calendar. http://www.hog.org/pharmacy/page/treatment-calendar. Accessed July 23, 2012.
  19. 18. Metcalf E. Manage hemophilia with a personal health record. HemAware. http://www.hemaware.org/print/458. Accessed July 23, 2012.
  20. 19. Schultz M. Hemolog. http://hemolog.com. Accessed July 23, 2012.
  21. 20. American Thrombosis and Hemostasis Network. ATHNadvoy: connecting patients and providers for better care—anywhere. http://www.athn.org/?q=content/tracking-your-bleeds-and-infusions. Accessed August 20, 2012.
  22. 21. Petrini P, Seuser A. Haemophilia care in adolescents—compliance and lifestyle issues. Haemophilia 2009;15(suppl 1):15-19.