Prevalence, Issues, and Clinical Challenges of Addressing Overweight/Obesity Among Persons with Hemophilia

 Expert Commentary

Introduction

In the United States, it is estimated that more than two-thirds of adults are overweight or obese, and this prevalence has been increasing in recent years.1 The Centers for Disease Control and Prevention (CDC) defines overweight as a body mass index (BMI) of ≥25.0 but <30.0 kg/m2, while those who are obese have a BMI >30.0 kg/m2.2 It is well established that obesity leads to multiple adverse effects on health, including weight-associated complications such as diabetes, cardiovascular disease (CVD), hypertension, reduced aerobic capacity, musculoskeletal disease, hyperlipidemia, stroke, sleep apnea, increased risk of some cancers, decreased quality of life, and greater health care costs for individuals and the health care system overall.3,4

Many patients with hemophilia (PWH) are now living longer than ever before, due in part to increased use of prophylaxis. However, many are developing comorbidities similar to those affecting the general population. Many of these conditions have never been studied in PWH due to their previously shorter lifespans. Overweight or obese PWH—including adults, teens, and children—face significantly greater health challenges from additional weight and mobility limitations. Above-normal weight can exacerbate joint pain and reduce joint mobility while increasing hemophilia-related health care costs. This Clinical Consult reviews the health aspects of overweight and obesity in children and adults with hemophilia that negatively affect quality of life and increase risk of serious comorbidities and death. Practical suggestions for preventing weight gain and reducing the prevalence of obesity among these patients are discussed, with the goal of improving overall health and outcomes.

 

Overweight/Obesity in Children

In the United States today, it is estimated that more than 30% of children are overweight, and 17% are obese.5 Some racial and ethnic minorities, including African Americans and Hispanics, are at greater risk compared with the overall population. The prevalence of overweight or obesity has more than tripled from 1971 to 2011. The proportion of severely obese children (ages 2-19 years) has also risen, from 4% in 1999–2004 to approximately 6% in 2011–2012.6 Many factors may account for this alarming rise, such as greater access and affordability of high-carbohydrate, high-fat, low-nutrient foods/fast foods and drinks; an increasingly sedentary lifestyle (eg, less need to walk to work or school), with less emphasis on physical activity and exercise; and more time spent with television, computer, electronic games, and other entertainment devices.

Can you describe the clinical impact of overweight/obesity in adults and children with hemophilia?

Heisel-Kurth

For some lower-income families, food insecurity can be a contributing factor to weight gain and obesity.7,8 Food insecurity is defined as “a limited ability to secure adequate food due to insufficient household resources.”7 According to US Department of Agriculture estimates, nearly 13% of US households (15.8 million households) experienced food insecurity at some point during the past year.9 Rates of food insecurity are higher in households with incomes at or below the federal poverty line, those with children headed by single women or single men, women and men living alone, and households headed by African Americans and Hispanics. While the precise relationship between food insecurity and obesity is not clear, some authors have proposed that anxiety and lack of resources related to food insecurity may result in poorer nutritional choices, such as calorie-rich, nutrient-poor foods.10 A study of food insecurity among 66,553 adults residing in 12 states found that obesity was more common in food-insecure adults compared with food-secure individuals (35% vs 25%) and indicated that 1 in 3 food-insecure adults are obese.7 Data suggest a relationship between food insecurity and obesity in adolescents, although results in children are less clear.8

The National Health and Nutrition Examination Survey (NHANES) survey found that obesity was significantly associated with personal food insecurity for children aged 6 to 11 years but not in those aged 2 to 5 years.11 Another study evaluating 438 preschool-aged children and their mothers reported that 25% of children from food-insecure households were overweight or obese.12 Although food insecurity and overweight were not significantly associated in this study, a substantial proportion of food-insecure children were either overweight or obese. Taken together, these data highlight the role of food insecurity in obesity and the need to increase access to affordable healthy foods for all adults and families.

What are the potential benefits of weight loss for PWH?

Sidonio

The cardiovascular impact of overweight and obesity in adults and children is well established. A cross-sectional analysis of NHANES data from overweight or obese children and young adults (ages 3-19 years) from 1999 to 2012 assessed the prevalence of cardiometabolic risk factors and their relationship to obesity severity.13 More severe obesity was associated with various risk factors including low high-density lipoprotein (HDL) cholesterol level, high systolic and diastolic blood pressures, and high triglyceride and glycated hemoglobin levels. There is ample evidence that childhood obesity also leads to adult obesity and weight-related comorbidities.14 For example, in the US Bogalusa Heart Study, overweight during adolescence was associated with an 8.5-fold increase in hypertension, an 8-fold increase in HDL cholesterol levels, a 2.4-fold increase in parental history of diabetes mellitus, and a 3-fold increase in high levels of low-density lipoprotein cholesterol as adults.15

Do most hemophilia treatment centers correctly assess weight in their hemophilia patients?

Reding

A wide range of comorbidities have been identified in children who are overweight or obese (Table 1).16 Additionally, obesity in children has been associated with psychological effects such as low self-esteem and depression, impacting quality of life.17 Early prevention and intervention strategies are needed to prevent or reduce obesity in youth, especially in children at high risk, and not wait until this leads to disease.

Table 1. Complications associated with childhood obesity16

Acute
  • Type 2 diabetes
  • Hypertension
  • Hyperlipidemia
  • Precocious puberty
  • Ovarian hyperandrogenism
  • Gynecomastia
  • Cholecystitis
  • Pancreatitis
  • Pseudotumor cerebri
  • Fatty liver
  • Renal disease
Orthopedic disorders
  • Slipped capital femoral epiphysis
  • Tibia vara
  • Blount disease
Liver and gall bladder dysfunction
  • Elevated transaminases
  • Cholecystitis
Physical and psychological
  • Depression
  • Eating disorders
  • Social isolation
  • Sleep disorders
Cardiovascular and endocrine
  • Hyperinsulinism and insulin resistance
  • Hypercholesterolemia
  • Hypertriglyceridemia
  • Low levels of high-density lipoprotein
  • Hypertension
  • Polycystic ovary syndrome
  • Coronary artery disease
  • Left ventricular hypertrophy
Cancer
  • Colorectal carcinoma
Long-term consequences
  • Ischemic heart disease
  • Short life span
  • Stroke
  • Sudden death

Adapted with permission of Pandita A, et al. Diabetes Metab Syndr Obes. 2016;9:83-89.

In addition to the medical impact, childhood obesity takes an economic toll on society. Medical costs for non-hemophilic obese children are higher compared with their normal-weight peers. One study estimated the incremental lifetime medical cost of an obese 10-year-old child, compared with a non-overweight child who maintains normal weight throughout adulthood, as ranging from $16,310 to $39,080 when weight gain through adulthood is accounted for, while other estimates are as high as $40,000.18,19 For this age cohort alone, a lifetime medical cost of $19,000 per child multiplied by the number of obese 10-year-olds today yields a total direct medical cost of obesity of about $14 billion. These estimates do not account for the impact of obesity on health-related quality of life or non-medical costs such as increased absenteeism from school and decreased work productivity in adulthood.

 

Prevalence of Overweight/Obesity in Hemophilia

The prevalence of combined overweight and obesity among patients with hemophilia appears to be comparable to that of the general population. A 2004 CDC study found that in adults with hemophilia (ages ≥20 years), 35% were overweight and 24% were obese.20 In comparison, a study evaluated 141 young men with hemophilia (ages 18-34 years ) who received care at 10 US federally funded hemophilia treatment centers (HTCs) between 2005 and 2013 and were enrolled in the Hemophilia Utilization Group Studies.21 Forty-eight percent of these young adults with hemophilia were either overweight or obese, and this proportion was higher in those who were 25-34 years of age compared with the younger cohort (Table 2: Prevalence of comorbidities in men with hemophilia21).

Total sample
(n = 141)
Age 18-24 years
(n = 75)
Age 25-34 years
(n = 66)
≥1 Comorbidity 89 (63%) 39 (52%) 50 (76%)
Arthritis

47 (33%)

18 (24%)

29 (44%)

Liver disease/hepatitis
HCV
67 (48%)
70 (50%)
22 (29%)
25 (33%)
45 (68%)
45 (68%)
HIV/AIDS

20 (14%)

2 (3%)

18 (27%)

Overweighta

33 (23%)

14 (19%)

19 (29%)

Obesea

34 (24%)

16 (21%)

18 (27%)

aOverweight defined as BMI ≥25 and <30 mg/kg2; obese as BMI ≥30 mg/kg2.
HCV, hepatitis C virus.
Adapted with permission of Curtis R, et al. Am J Hematol. 2015;90(suppl 2):S11-S16.

The prevalence of obesity among PWH can vary regionally in the United States. A study of hemophilia patients in Mississippi, for example, found that 51% were either obese or overweight; in adults (ages ≥20 years), 36% were obese and an additional 32% were overweight.22 Race and severity of hemophilia were not significantly associated with overweight and obesity in this study. The high prevalence of obesity in this population of PWH may relate in part to this state having some of the highest rates of obese adults (35.5%) and youth (18.9%) in the United States.23 These data suggest that Mississippi may have one of the highest proportions of obese hemophilia patients in the country, with obvious implications for health care costs at the state level.

A 2014 survey of 90 federally funded HTCs in the United States found that 87% considered obesity to be a major concern for their pediatric and adult hemophilia patients.3 One-third of centers had a nutritionist available to address weight concerns, and of the remainder, 61% referred patients for nutritional counseling when needed. Nearly 90% of centers did not have a protocol in place for addressing healthy weight practices, although half indicated that guidelines are needed. Further education of health care professionals is warranted, as evidenced by the fact that most HTCs did not routinely use recommended guidelines to calculate BMI in order to accurately identify people who were overweight or obese.

Obesity and Other Comorbidities in Patients with Hemophilia

Children with hemophilia are more prone to become overweight or obese for multiple reasons. Some overprotective parents and health care professionals may feel such children are too frail and prone to injury and bleeding, and they may discourage or restrict their physical activity. Unfortunately, this mainly serves to reinforce the child’s lack of activity and promotes the overweight condition and resulting impact on joints. Young patients with hemophilia or other chronic conditions can be less physically fit than their normal peers, with lower aerobic capacity and shorter distance achieved in a 6-minute walk test.24,25

Due to the availability and widespread use of safe factor concentrate and recombinant factors for patients with bleeding disorders, the risk of infectious diseases such as hepatitis and HIV has been greatly reduced. Compared with the 1970s, many individuals with hemophilia are now surviving into their sixties or seventies. A comparison of age distributions of PWH in 2011 and 2015 indicates that the proportion of individuals older than 65 years has risen from 2% to 4%.26 With this increased survival, many are developing age-related comorbidities common in the older non-hemophilia population but not frequently seen heretofore in PWH. Comorbidities now commonly observed in older PWH include hypertension, obesity, and diabetes; these can predispose patients to chronic conditions such as CVD and chronic kidney disease.26 A retrospective chart review of 63 patients older than 40 years, seen at a regional HTC between 2007 and 2010, noted that multiple comorbidities may be the rule rather than the exception in this aging population.27 Apart from hemophilia, all patients studied had at least 1 comorbid condition, and the majority had between 3 and 6 comorbidities, including chronic hepatitis C, hypertension, HIV, chronic arthropathy, renal disease, and overweight/obesity. Approximately 65% of patients in this study were considered overweight or obese (40% and 25%, respectively). Interestingly, overweight/obesity was more prevalent among patients with mild hemophilia (72%), as reported previously.28 Other studies have similarly reported multiple comorbidities in aging PWH, such as CVD, diabetes, cancer, and osteoporosis.29 The presence of multiple comorbidities and the need for polypharmacy in aging PWH, coupled with a lack of prospective studies and absence of clear treatment guidelines,26,27 present challenges to practitioners for effective treatment and long-term management of these conditions in this special population.29,30

Adults with hemophilia may be at higher risk of CVD compared with the general population. A 5-year study of PWH 35 years of age and older found that compared with US non-Hispanic white males, PWH had about twice the prevalence of coronary artery disease, stroke, and myocardial infarction.31 A Canadian study similarly evaluated risk factors for CVD in an older (≥35 years) population of patients with hemophilia A and B.32 Identified risk factors included hypertension (31%), diabetes mellitus (11%), smoking (22%), obesity (28%), and dyslipidemia (22%). The authors noted that “there is a clear need for ongoing research to help develop evidence-based guidelines for the management of CVD risk factors and events in patients with hemophilia.” Children with hemophilia who are severely obese similarly can have increased cardiovascular risk factors such as low levels of HDL, increased cholesterol level, high systolic and diastolic blood pressure, high levels of triglycerides and hemoglobin A1C, and heart disease. They are also at higher risk for obesity-related issues such as type 2 diabetes, metabolic syndrome, lower bone density, and depression.33

Overweight/obesity may predispose hemophilia patients to hypertension, which can lead to CVD and stroke.34 Adult PWH were found to have a significantly higher prevalence of hypertension compared to normal adults (49% vs 32%), and fewer PWH were effectively controlled when treated for hypertension. Additionally, patients with moderate or severe hemophilia tended to have an increased risk of hypertension compared to those with mild hemophilia (≈1.5-fold higher odds ratio). Patients with hemophilia also are at increased risk for intracranial hemorrhage (ICH),35 and hypertension is the most significant risk factor for ICH in the general population.36 Since obesity is a well-known risk factor for hypertension, the combination of these factors in PWH can lead to morbidity and mortality arising from CVD and kidney disease.

In general, PWH do not appear to be at increased risk of cancer compared with the general population. Due to an elevated risk of HCV infection in the past, they are at increased risk of hepatocellular carcinoma (HCC) associated with chronic HCV infection, which explains why HCC was a significant cause of death in PWH in the past.37 Adult PWH also have a greater risk of developing chronic kidney disease (due in part to hypertension and renal failure).26 Older patients with hemophilia must be monitored for typical age-related diseases such as osteoporosis, cancer, and cognitive decline.

Relationship Between Obesity, Joint Bleeding, and Range of Motion

While all the effects on obesity on hemophilia have not been fully characterized, it is clear that overweight and obesity contribute to the progression of arthropathy. Overweight people in the general population (ie, those without hemophilia) have an increased risk of joint disease, presumably from the greater stress on weight-bearing joints.38 Obese individuals with hemophilia face an even higher risk due to the combined effects of arthropathy resulting from recurrent joint bleeds and arthritic changes related to their additional weight.

In children with severe hemophilia, the onset of joint bleeding and joint pain can lead to decreased activity and increased risk of obesity. The greater weight load further strains already damaged weight-bearing joints, particularly knees and ankles, and contributes to further joint damage and pain, thus reinforcing inactivity.39 This futile cycle can result in a worsening of arthropathy and greater immobility and physical functioning (Figure 1). Conversely, a reduction in weight may result in fewer joint bleeds, less joint pain, and improved mobility and quality of life.

Figure 1. Proposed relationship between obesity and arthropathy39

Figure 1

Reprinted with permission of Majumdar S, et al. Haemophilia. 2012;18:e82-e84.

Gupta and colleagues evaluated 286 males older than 2 years and with no target joint involvement at enrollment but subsequently developed ≥1 affected joint, and who received either secondary prophylaxis or on-demand treatment.40 Using multivariate analysis, they found that obesity or overweight, along with age older than 5 years at target joint development and the presence of inhibitors, was associated with a significantly increased rate of hemarthroses. The incidence rate of joint bleeds in obese individuals was 10% higher than that of the normal or underweight group.

Hemophilic arthropathy occurs more commonly in overweight and obese hemophilia patients, and the decrease in joint range of motion (ROM) that arises from joint bleeds correlates with increased BMI. Data from the Universal Data Collection (UDC) project, including more than 4300 males with hemophilia (ages 2-19), was analyzed to determine limitations in ROM and associated factors.41 When all patients were considered, joint ROM limitation was associated with age, non-white race, and increased BMI. In those individuals with severe hemophilia, limited ROM was also associated with number of bleeds, and this was greater for patients with inhibitors or recent orthopedic procedures. ROM limitation was apparent as early as age 10 and increased thereafter in patients with severe or moderate disease, although the rate of increase was greatest for those with severe hemophilia (Figure 2). Since BMI is a potentially modifiable risk factor that is significantly associated with decreased ROM, these results suggest that interventions designed to decrease BMI could improve ROM or at least slow the loss of limitation in hemophilia.

Figure 2. Limitations in joint range of motion (ROM) in young males with hemophilia41

Figure 2

Linear regression based on factors found to be independently associated with percentage of ROM limitation for males with severe, moderate, or mild hemophilia 2 to 19 years of age. Adapted with permission of Soucie JM, et al. Blood. 2004;103:2467-2473.

Using the UDC database, Monahan and colleagues evaluated 15 potential predictors for poor outcomes of physical functioning related to bleeding in boys with hemophilia. Based on multivariate analysis, except for underlying disease severity, only obesity and medical insurance coverage with Medicaid (rather than private insurance) were associated with multiple predictors of limited physical functioning including days missed from school or work and the need for assistive devices or wheelchair.42 The results suggest that efforts aimed at preventing or reducing obesity in youth with hemophilia could also decrease loss of physical functioning. They also indicate that ensuring adequate insurance coverage for PWH is critical, given the high annual cost of prophylaxis.

Impact of Obesity on Calculation of Factor Dose and Infusion

Increased weight significantly increases the amount of clotting factor needed to maintain adequate trough levels, but there is not universal agreement on how this should be calculated for overweight/obese individuals. The amount of factor VIII (FVIII) required is typically calculated using the formula [body weight (kg) × desired FVIII increase (%)]/2. This assumes that each FVIII unit infused per kilogram of body weight increases the circulating FVIII level by 2% (in vivo recovery). Consequently, heavier individuals receive more factor than those of normal weight, but this approach is complicated by the fact that fat tissue has less blood supply than muscle/lean tissue. Usage of clotting factor concentrate (CFC) has been compared in obese and non-obese patients with severe hemophilia A. Obese patients were found to use 1.4 times as much CFC/patient-month compared with non-obese patients, as well as higher plasminogen activator inhibitor type 1 levels, although the median number of bleeds per month was similar.43

How does weight affect the proper calculation of factor dosing in PWH?

Kurth

Calculation of correct FVIII dosing is typically based on BMI using actual body weight, but ideal body weight (IBW) may be more accurate for overweight (and underweight) patients. Some investigators have proposed using IBW rather than actual weight to calculate FVIII dose, since recovery increases with body weight.44,45 In a study of more than 200 PWH (26% who were overweight and 17% obese), FVIII recovery was found to be significantly dependent on BMI but not on age. Recovery was higher in patients with a BMI ≥29.6 kg/m2 (median recovery of 2.70 rather than 2.0) (Figure 3).45

Other studies have suggested that in addition to BMI, fat mass index should also be considered when calculating FVIII dosing.46 Given the large proportion of PWH who are overweight or obese, calculation of factor dose could be inaccurate if providers follow the standard approach of using actual rather than IBW and a universal recovery value of 2% to determine FVIII dosing. A pharmacokinetic study in 6 obese hemophilia A patients determined that compared with standard dosing, IBW-based dosing resulted in comparable pharmacokinetics and hemostatic efficacy for prophylaxis and surgery.47 Yet IBW dosing resulted in an average 49% reduction in factor use per patient over a 3-month period, for an annualized savings of $133,000 per patient. These data, if confirmed in larger studies, could have significant economic implications for factor dosing. An ongoing randomized clinical trial at the University of Washington is evaluating the pharmacokinetics of FVIII dosing in overweight and obese PWH, comparing dosing based on ideal or actual body weight.

Figure 3. Recovery of FVIII varies according to BMI45

Figure 3

Reprinted with permission of Henrard S, et al. J Thromb Haemost. 2011;9:1784-1790.

Overweight or obese PWH may also face challenges related to self-infusion. An analysis of data from 10,814 men with hemophilia A or B (45% with severe disease) aged 6-79 years, enrolled in the UDC surveillance project, revealed that overweight or obese teens and adults were significantly less likely to practice home infusion (HI) or self-infusion (SI) compared with those of normal weight, and had a lower prevalence of prophylaxis use.48 Although not specifically measured in this study, the authors hypothesized that reductions in HI and SI may be attributed to the increased difficulty of finding veins and successful venipuncture related to adiposity. Decreased use of HI and SI can potentially lead to delayed treatment of bleeds and reduced effectiveness of infusions, placing those with elevated BMI at risk of hemophilic complications. Education of parents regarding the dangers of above-normal weight in children and guidance for adults in maintaining a healthy weight should be a priority for hemophilia treatment center staff.

Pharmacoeconomic Impact

The financial impact of overweight or obesity on cost of factor prophylaxis alone could have significant financial implications, since approximately 60% of PWH are overweight or obese. Majumdar and colleagues evaluated the potential pharmacoeconomic impact of obesity in PWH by performing a hypothetical cost assessment of weight reduction.49 This analysis was based on a chart review of patients in Mississippi who were 2-18 years of age and on prophylaxis for severe hemophilia (16 with hemophilia A; 4 with hemophilia B) and were above their IBW. Of the 20 children who were above their IBW, 13 (65%) were considered either overweight or obese. Most patients with hemophilia A received prophylaxis every other day, with twice-weekly prophylaxis for those with hemophilia B. For this sample of 20 patients, using ideal rather than actual body weight could result in an annual total cost savings of $2 million when factor prophylaxis alone is considered. Factor costs represent the majority of annual health care expenses for hemophilia, depending on disease severity and treatment regimen used, accounting for 45% to 93% of total costs in one study.50 Since factor usage is based on patient weight, reduction in weight for PWH could achieve substantial cost savings and thus significantly reduce the economic burden of this disease. Moreover, as discussed above, inaccuracies in calculation of dose based on BMI rather than IBW could result in overdosing, which wastes expensive factor. Decreases in the proportion of overweight or obese individuals could therefore generate substantial annual cost savings when factor use alone is considered. Such considerations are especially relevant given the higher cost of many extended half-life factor products now available. This does not account for additional savings in health care costs that may be achieved through weight reduction that are unrelated to hemophilia treatment.

Assessment of Overweight/Obesity in PWH

BMI is considered the best indicator for overweight or obesity in children and adolescents.51 Health care professionals should therefore measure height and weight of PWH at each office visit in order to calculate BMI, and they are encouraged to follow published current guidelines to ensure consistency. In the United States, childhood obesity is usually defined as a BMI above the 95th percentile for age and sex, with overweight defined as a BMI greater than the 85th percentile. While various growth charts exist for determining weight gain and obesity in children, those most commonly used for assessing BMI are from the CDC, which provide age- and sex-specific standards for children 2 to 18 years of age.52 As stated previously, the CDC defines adults with a BMI >25.0 but <30.0 kg/m2 as overweight, while those with a BMI >30.0 kg/m2 are considered obese.2

Define the term “food insecurity".

How can food insecurity contribute to obesity in adults and children?

Kurth

If PWH are determined to be overweight or obese, these findings and their health implications, particularly with regard to hemophilia, should be clearly explained to the patient and/or family. The potential future effects of obesity on hemophilia may not always be apparent, particularly to children and teens. A nutritionist from the HTC team or an outside consultant can provide nutritional counseling, dietary plans, and exercise regimens to prevent further weight gain and ideally help the patient start to lose weight and learn healthier diet and lifestyle choices.

 

Sports and Physical Activities in Overweight/Obese Patients with Hemophilia

Clinicians disagree as to whether children and teens with hemophilia can safely participate in sports and other physical activity. In general, these youths are thought to be as fit as their healthy peers with respect to overall aerobic capacity and muscle strength.53 Data suggest that PWH, including those who are overweight or obese, can safely participate in physical activities. A review of the literature indicates that in many cases PWH could participate in sports and other activities at levels similar to or greater than that of the general population.54 For example, a survey of patients with hemophilia B reported that 62% of participants aged 15-64 years engaged in a high level of physical activity and 29% had a moderate activity level.55 Those with high levels of physical activity had better health-related quality of life than individuals with lower activity levels, while overweight subjects had lower levels of physical activity and poorer quality-of-life scores. However, many of these studies did not report if or how patients were treated with replacement clotting factor before such activities. With appropriate prophylaxis (possibly using extended half-life recombinant factors) to guard against bleeding during rigorous activities and implementation of safety precautions against head trauma, PWH can be physically active and participate in sports and other exercises. Studies have demonstrated that youth with moderate or even severe hemophilia can participate in regular sports, with minimal risks, and realize improvements in fitness and health-related quality of life.53,56 In one report, boys participating in such activities had fewer lost school days compared with a more sedentary cohort and spent less time in front of the television or on computer games.56

An Australian study followed 104 children and adolescent boys (ages 4-18 years) with moderate or severe hemophilia A or B who participated in various vigorous physical activities and were monitored for bleeds.57 Compared with inactivity or low-risk activities (eg, swimming), other more vigorous collision sports (eg, basketball, wrestling) were associated with a transient increase in the risk of bleeding. However, since the increased relative risk was short-lived, the absolute increase in bleeding risk associated with these activities was considered to be small. Other investigators have come to similar conclusions, with one study reporting children with severe hemophilia A or B developing less than 1 bleed or injury per season, even when participating in high-impact activities.33 Based on logistic regression analysis and adjusting for prophylaxis frequency, level of athletic participation was not a significant prognostic factor for joint hemorrhage. These studies suggest that the risk of bleeding events in this population represents only a small proportion of total bleeds and thus should not preclude PWH from engaging in vigorous high-impact activities if supported by adult coaching and supervision. Similarly, overweight or obese PWH should be encouraged to participate in regular physical activity in order to stay healthy, lose weight and/or prevent further weight gain, and improve their overall quality of life.

How big a problem is food insecurity in the US?

Kurth

Since sports vary with regard to intensity and risk of trauma or bleeding, the National Hemophilia Foundation has developed a patient brochure, Playing It Safe (available at www.hemophilia.org), that promote sports and physical activity in adolescents and adults and suggests options for activities (Figure 4).58 The brochure notes that the level and/or type of activities may need to be modified for a given patient and emphasizes the need for them to recognize and promptly report bleeds to their health care provider. Before initiating an exercise program, PWH should consult with their physician or HTC team for guidance on appropriate exercises. Patients may require an individualized prophylaxis regimen in order to ensure higher peak factor levels before participating in rigorous sports or other high-risk activities.59,60

Figure 4. Sports activities by risk level58

Figure 4

Reprinted with permission from Playing It Safe, National Hemophilia Foundation.58

Nutritional Guidelines and a Web-based Nutritional Resource

In 2011, the US Department of Agriculture (USDA), in conjunction with the US Department of Health and Human Services (USDHHS), initiated a public health campaign to introduce new dietary guidelines to encourage better nutrition among Americans. Called “My Plate” (available at www.MyPlate.gov), the new guidelines replace the well-known food pyramid that was used to teach generations of Americans about nutrition. My Plate is an interactive website and educational resource focusing on balancing calories with physical activity. The largest portion (fully one-half) of My Plate is filled with fresh fruits and vegetables; the new guidelines stress the concept of filling half of one’s plate with these. Grains and proteins each represent less than one quarter of the plate. Instead of mainly meats, the protein group now includes other protein-rich foods such as fish, poultry, eggs, shellfish, beans, nuts, and seeds. The diary group is represented by a circle next to the plate and is defined as fat-free or low-fat milk or yogurt. The MyPlate website includes materials designed specifically for the general public, educators, and healthcare professionals. It advises that “eating healthy is a journey shaped by many factors, including our stage of life, situations, preferences, access to food, culture, traditions, and the personal decisions we make over time.”

ChooseMyplate.gov

Reproduced with permission from the USDA’s Center for Nutrition Policy and Promotion. For information about food and health, go to ChooseMyPlate.gov.

Interventions

Pediatric Hemophilia Patients
Preventing the development of obesity in children with hemophilia (and in non-hemophilic youth) is a key public-health goal, since childhood-onset obesity frequently persists into adulthood. Health care professionals therefore should focus on prevention and intervention strategies in children to help reduce the risk of obesity, especially in those patients who are at high risk, and not wait until they become overweight or obese. This can be challenging, though, as some ethnicities (eg, Hispanics) may equate chubbiness in a child with health.

Similar to the non-hemophilia population, early intervention and prevention measures are more effective compared with later efforts to lose weight once youth have already become obese. Three levels of prevention are recognized for management of childhood obesity16:

  • Primordial prevention: maintaining a healthy weight and normal BMI during childhood and teen years
  • Primary prevention: preventing children who are overweight from becoming obese
  • Secondary prevention: treating overweight and obesity to reduce weight and address comorbidities

In general, increasing physical activity level and changing diet and eating habits are essential for promoting weight loss in any patient. A comprehensive intervention should include a structured diet, exercise, and behavioral modification, ideally coordinated with a multidisciplinary obesity care team. Specific approaches that can help prevent weight gain and development of childhood obesity include educating youth and parents on the multiple benefits of healthy nutrition and healthy lifestyles; providing information on short- and long-term clinical consequences that overweight/obesity can have on arthropathy, joint pain, factor use, costs, and quality of life; discussing potential benefits that weight reduction today could have on reducing or delaying progression of hemophilia-related sequelae later in life; and teaching parents how to provide positive reinforcement and praise for desired behaviors in their children. Those children who are already significantly overweight or obese may benefit from implementation of an individualized diet and exercise plan with the help of a pediatric nutritionist, with referral to an obesity clinic if available. Practical guidelines to slow or reverse weight gain and development of obesity in children with hemophilia (and non-hemophilic youth) are listed in Table 3.

Table 3. Practical approaches for preventing development of overweight/obesity in children with hemophilia

  • Remove easy access to unhealthy foods and drinks
  • Provide a wide variety of healthier food options
  • Limit intake of sugar and high-calorie drinks and snacks
  • Avoid letting toddlers/small children develop a taste for sweet or fatty foods
  • Promote greater consumption of fruits and vegetables, daily healthy breakfasts, home-cooked meals, and smaller portion sizes
  • Limit access to TV and computer and other electronic devices to reduce sedentary activity
  • Encourage daily exercise and physical activity
  • Avoid parental restriction of sports and rigorous activities (factor levels may need to be modified for some high-risk sports)
  • Maintain regular prophylaxis to help ensure safe participation in sports for children, and minimize bleeding complications and adverse effects on joints

Most experts stress that prevention and early intervention are key to averting development of obesity in children. Pandita and colleagues recently proposed a set of age-appropriate guidelines aimed at monitoring food consumption and activity levels, and encouraging adoption of positive behaviors and eating habits, spanning from the perinatal period to adolescence.16

  • Perinatal: ensure adequate prenatal nutrition with optimal maternal weight gain, good blood sugar control in diabetics, and postpartum weight loss with exercise and nutritional counseling
  • Infancy: early initiation of breastfeeding, which is maintained for 6 months, followed by introduction of solid foods; maintain balanced diet; avoid unhealthy calorie-rich snacks; regularly monitor for weight gain
  • Preschool: provide nutritional education to parents and children to encourage healthy eating habits; offer early exposure to healthy foods; closely monitor weight gain
  • Childhood: monitor weight and height to prevent excessive prepubertal adiposity; offer nutritional counseling; encourage daily physical activity
  • Adolescence: prevent weight gain that can occur after growth spurt; maintain healthy eating behaviors; reinforce need for daily exercise and activity
  • Promote nutritional goals and tools, such as the “traffic light” diet that identifies healthy items as “green” and unhealthy items as “red”61

Adults with Hemophilia

Unfortunately, most teens who are overweight or obese tend to remain so as adults. Moreover, current treatment approaches are not as effective at higher levels of obesity compared with lower levels, providing further impetus to prevent weight gain, and particularly obesity, when patients are younger rather than in adulthood.

Many of the same approaches described above for preventing or reversing weight gain in younger PWH can also apply to adults, but weight loss in older patients is often more difficult for a variety of reasons. Adults with hemophilia typically have varying degrees of preexisting arthropathy and pain, which can serve as a deterrent to exercise. Decreased flexibility, joint ROM, strength, and proprioception in older PWH can impair balance and increase risk of falls, leading to fracture or intracranial hemorrhage. Some patients, however, already may have gained weight due to lack of exercise or suffer from comorbidities such as diabetes. Adults in general spend too much time on electronic devices and not enough participating in exercise and other activities. And, in contrast to young children, poor diet and eating habits are more ingrained in adults, making it harder to change.

Should adolescents with hemophilia participate in sports and other physical activities?

Don’t adolescents with hemophilia need to be careful so they don’t have a bleed?

What about the precautions?

Kurth

While data are limited, a number of small studies have found that exercise programs can improve strength, ROM, flexibility, and quality of life in adults with hemophilia. Various approaches include walking, aquatic exercise or hydrotherapy, sports, and physiotherapy.62-64 In addition, general interventions for adults with hemophilia who are overweight or obese include:

  • Encourage prevention of weight gain and maintenance of target weight
  • Provide education on clinical consequences and importance of overweight/obesity on hemophilia and potential benefits of losing weight
  • Discuss and help implement behavior modification program that could include:
    • Changes in diet
    • Limited alcohol intake due to high caloric content
    • Education (of patients, families, and health care professionals) on importance of physical activity and healthy diet (eg, healthy vs less healthy food choices) and healthy lifestyles
    • Exercise program, with modifications due to hemophilia as needed (including possible increased factor need); use of personal trainer with knowledge about bleeding disorders
    • Consultation with nutritionist who is familiar with hemophilia to establish an individualized dietary plan and exercise program

Case Study

The potential impact of weight loss on quality of life for PWH can be illustrated by a case study of an obese (283-lb) 27-year-old man with a history of severe hemophilia A.39 This patient had documented all joint bleeds for approximately 9 months before and 4 months following initiation of a structured program that combined nutrition education, behavior modification, and exercise instruction. Calorie intake and expenditure were not recorded, although his weight was measured weekly during the weight management program, and weight data were available from his visits to the HTC.

At the end of the 4-month program the patient had lost 35 lb, with a decline in BMI from 38.3 at baseline to 33.5.39 This decrease correlated with a reduction in bleeding in ankle, elbow, and knee joints, with a correlation coefficient (r2) between rate of bleeding and weight over time of 0.418, 0.927, and 0.899, respectively (Figure 5). While conclusions are limited on the basis of a single patient, these data suggest that risk of joint bleeds could be associated with a patient’s weight and that a weight-loss program may be effective in reducing the number of bleeds as well as improving overall health. The authors postulated that obesity may induce a state of systemic inflammation with upregulation of cytokine expression, which could play a role in synovial inflammation. Larger studies are needed to confirm these clinical correlations and evaluate the impact of weight loss in PWH on other domains such as CVD and bone health.

Figure 5. Correlation of weight loss and joint bleeds in a patient with hemophilia enrolled in weight-loss and exercise program39

Figure 5

Shown are changes in weight (solid lines) and joint bleeds (dotted lines) in ankle (a), elbow (b), and knee joints (c) over time. (Day 0 indicated start of a 4-month weight-reduction program.) Correlation coefficients (r2) between rate of bleeding and weight over time are indicated at right.
Reprinted with permission of Majumdar S, et al. Haemophilia. 2012;18:e82-e84.