Activity Levels Vary Greatly Across Patients, With Effects Far From Clear

Children and teenagers with hemophilia are considerably more physically active than adult patients, possibly reflecting more recent emphasis on the benefits of exercise and the arrival of better treatments, according to a recent review study.

Yet, how physically activity relates to bleeding events remains unclear, its researchers wrote, and long-term studies are needed to clarify this potential association, and in the context of different treatment regimens.

The study, “A systematic review of physical activity in people with haemophilia and its relationship with bleeding phenotype and treatment regimen,” was published in the journal Haemophilia.

A team of researchers in Ireland and Austria performed a systematic literature review that focused on assessing physical activity levels among people with hemophilia, as well as investigating the possible relationship between physical activity and bleeding episodes.

They identified 1,902 potentially relevant studies published as of December 2020.

Of these, 36 studies covering a total of 3,185 patients (1,361 children up to age 18, and 1,791 adults up to age 85) were selected to be included in the analysis.

About 1,701 of these patients had hemophilia A, and 887 had hemophilia B. Regarding disease severity, 732 hemophilia cases were considered to be mild, 676 moderate, and 1,876 severe.

Physical activity levels were largely patient-reported: assessed using diaries, surveys, questionnaires (in 15 studies), and interviews (in 11 studies). In three studies, researchers used accelerometer devices — worn on a wrist or the hips — to measure physical activity for one week.

Overall,  activity levels were highly variable among patient groups distinguished by age, and disease type and severity.

Participation in sports was reported in 16 studies. Considerable levels of sport engagement (seen in more than half of the participants) was found in 10 studies, and a wide variety of sports, both high and low impact, were described in 19 studies.

Fifteen studies, involving patients ages 4–69, looked at activity levels across categories of hemophilia severity. In five studies, those with non-severe disease forms reported higher levels of physical activity or sport engagement, while 10 other studies found no differences in these levels among the patients groups.

In addition, two studies identified people with severe forms of hemophilia whose levels of physical activity were higher than those with non-severe disease.

“Levels of PA [physical activity] and participation in sport varied markedly amongst the heterogeneous samples of PWH [people with hemophilia],” the researchers wrote.

“Although age-related decline in PA is also a common trend seen in the general population, lower levels of PA amongst older adults with haemophilia may also be attributable to less promotion of PA when they were young due to less optimal treatments, resulting in more bleeds and joint damage,” they added, as could difference in socio-economic status, culture and personality.

Bleeding was reported in 21 studies, and the relationship between bleeds and physical activity was investigated in 14 studies enrolling children and adults (ages 4–66).

The prevalence of sport- or exercise-related bleeds was again variable across studies and patients. While some studies reported a correlation between bleeds and certain types of physical activity, others failed to identify any relationship.

“The relationship between PA and bleed rate remains inconclusive. This was mostly due to heterogeneity in study sample characteristics, methods and the definition of bleeds and volume of PA,” the researchers wrote.

About 849 patients received on-demand treatment for their bleeds, while 1,617 were on a prophylactic, or preventive, treatment regimen.

In a large survey study, a negative impact on engagement in activity, including changes to treatment dosing and timing before vigorous activity, was reported by patients with severe hemophilia or those on routine treatment.

Another study found hemophilia A patients who were more adherent to prophylaxis engaged more often in physical activity than those with lower adherence rates.

“The positive influence of prophylaxis appears to reduce the risk of bleeds associated with PA,” the researchers wrote.

Their work had several limitations, including possible omissions of studies and incomplete data in abstracts reported at science conferences.

Still, “this systematic review suggests that levels of PA vary markedly between individual adults and children with haemophilia,” the researchers wrote.

“The use of validated outcome measures of PA and more robust reporting of bleeds and treatment regimen are warranted in future research, especially in a rapidly evolving era of new treatments,” they concluded, adding that better activity studies will address “an important clinical unmet need.”