Habitual physical activity in Dutch children and adolescents with haemophilia.
ABSTRACT For patients with haemophilia, a physically active lifestyle is important to maintain musculoskeletal health and to prevent chronic diseases, such as cardiovascular disease. Therefore, we studied physical activity levels, in Dutch children and adolescents with haemophilia as well as its association with aerobic fitness and joint health. Forty-seven boys with haemophilia (aged 8-18) participated. Physical activity was measured using the Modifiable Activity Questionnaire (MAQ) and was compared with the general population. Aerobic fitness was determined using peak oxygen uptake (VO(₂peak)). Joint health was measured using the Haemophilia Joint Health Score (HJHS). Associations between physical activity, joint health and aerobic fitness were evaluated by correlation analysis. Subjects were 12.5 (SD 2.9) years old, had a Body Mass Index (BMI) of 19.5 (SD 3.1; z-score 0.5) and a median HJHS score of 0 (range 0-6). Cycling, physical education and swimming were most frequently reported (86%, 69% and 50% respectively). Children with severe haemophilia participated significantly less in competitive soccer and more in swimming than children with non-severe haemophilia. Physical activity levels were similar across haemophilia severities and comparable to the general population. VO(₂peak) kg⁻¹ was slightly lower than healthy boys (42.9 ± 8.6 vs. 46.9 ± 1.9 mL kg⁻¹ min⁻¹; P = 0.03). Joint health, aerobic fitness and physical activity showed no correlation. Dutch children with haemophilia engaged in a wide range of activities of different intensities and showed comparable levels of physical activity to the general population. Aerobic fitness was well preserved and showed no associations with physical activity levels or joint health.
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ABSTRACT: Haemophilia A and B are hereditary X-linked disorders due to deficiency (or absence) of coagulation factor VIII or IX, respectively. Bleeding risk is related to the severity of factor deficiency. Repeated joint bleeding can lead to a severe haemophilic arthropathy resulting in disabilities. Outcome measurements in persons with haemophilia (PWH) have been limited to laboratory evaluation (factor VIII or IX levels) and clinical outcomes (such as bleeding frequency), morbidity (for example linked with arthropathy) and mortality. Due to the new standard of care of PWH, there is a need to consider other outcome measures, such as the early detection and quantification of joint disease, health-related quality of life (QoL) and economic or cost-utility analyses. To investigate this, we performed a 10-yr systematic overview of outcome measures in haemophilia. Only clinical trials including at least 20 patients with haemophilia A or B were included. To facilitate the search strategy, eight issues of outcome measures were selected: physical scores, imaging technique scores, functional scores, QoL measurement, mortality, bleeding frequency, cost and outcome and bone mineral density. The results of these will be discussed. Clearly defined outcomes in haemophilia care are important for many reasons, to evaluate new treatments, to justify treatment strategies, to allow a good follow-up, to perform studies and to allocate resources. The use of such scoring systems is clearly recommended by experts in haemophilia care. However, most centres do not perform such scores outside clinical trials due to reasons such as lack of time and resources.European journal of haematology. Supplementum 08/2014; 76:2-15.
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ABSTRACT: The current widespread use of prophylaxis in developed countries has enabled greater participation in physical activity. However, there are no data available on leisure-time physical activity in Australian children with haemophilia. The data reported here were obtained from a case-crossover study nested in a prospective cohort study of 104 boys with moderate and severe haemophilia followed for one year. Each child's physical activity was assessed using a modifiable physical activity questionnaire (Kriska's MAQ) administered at baseline, and a one-week prospective activity diary at a randomly determined time. Children were aged 4-18 years. The median time spent in sport or leisure-time physical activity in the preceding year was 7.9 h/week (IQR 4.6 to 12.9). The median time spent in vigorous physical activity was 3.8 h/week (IQR 1.6 to 6.4) and in moderate and vigorous physical activity 6.4 h/week (IQR 3.7 to 10.0). The median small-screen time was 2.5 h/day (IQR 0.5 to 2.5). Forty-five per cent of all children and 61% of children over the age of 10 years played at least one competitive sport. Averaged across one week, 43% of all children met the Australian government physical activity guidelines for children and 36% met the guidelines for small-screen time. This study provides the first data regarding leisure-time physical activity in children with haemophilia living in Australia. The majority of Australian children with haemophilia are not meeting the national physical activity and small-screen time guidelines.Haemophilia 07/2012; · 3.17 Impact Factor
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ABSTRACT: Our objective was to provide a synthesis of measurement properties for performance-based outcome measures used to evaluate physical function in children with haemophilia. A systematic review of articles published in English using Medline, PEDro, Cinahl and The Cochrane Library electronic databases was conducted. Studies were included if a performance-based method, clinical evaluation or measurement tool was used to record an aspect of physical function in patients with haemophilia aged ≤ 18 years. Recording of self-perceived or patient-reported physical performance, abstracts, unpublished reports, case series reports and studies where the outcome measure was not documented or cross-referenced was excluded. Description of outcome measures, patient characteristics, measurement properties for construct validity, internal consistency, repeatability, responsiveness and feasibility was extracted. Data synthesis of 41 studies evaluating 14 measures is reported. None of the outcome measures demonstrated the requirements for all the measurement properties. Data on validity and test-retest repeatability were most lacking together with studies of sufficient size. Measurement of walking and muscle strength demonstrated good repeatability and discriminative properties; however, correlation with other measures of musculoskeletal impairment requires investigation. The Haemophilia Joint Health Score demonstrated acceptable construct validity, internal consistency and repeatability, but the ability to discriminate changes in physical function is still to be determined. Rigorous evaluation of the measurement properties of performance-based outcome measures used to monitor physical function of children with haemophilia in larger collaborative studies is required.Haemophilia 11/2013; · 3.17 Impact Factor
Joint Health, Functional Ability and
Physical Activity in Haemophilia
Gewrichtsstatus, Functionele Mogelijkheden en Fysieke Activiteit
bij Patiënten met Hemofilie
Willem Gerardus Groen
Joint Health, Functional Ability and Physical Activity in Haemophilia
Thesis, Utrecht University, The Netherlands
© 2011, Wim Groen
No part of this thesis may be reproduced, stored or transmitted in any way or by any
means, without prior permission of the author.
The studies presented in this thesis were financially supported by a grant from Pfizer.
The priniting of this thesis was financially supported by:
Divisie Kinderen (UMC Utrecht), Pfizer BV, CSL Behring BV, Novo Nordisk BV,
Lode BV and Stichting Sanquin Bloedvoorziening.
Printed by: Uitgevery Box Press, Oisterwijk
Cover design: Erik de Hart
Lay-out: Wim Groen
Joint Health, Functional Ability and
Physical Activity in Haemophilia
Gewrichtsstatus, Functionele Mogelijkheden en Fysieke Activiteit
bij Patiënten met Hemofilie
(met een samenvatting in het Nederlands)
ter verkrijging van de graad van doctor aan de Universiteit Utrecht
op gezag van de rector magnificus, prof.dr. G.J. van der Zwaan,
ingevolge het besluit van het college voor promoties
in het openbaar te verdedigen op
donderdag 15 december 2011 des middags te 2.30 uur
Willem Gerardus Groen
geboren op 17 november 1981 te Hoorn
Prof.dr. P.J.M. Helders
Prof.dr. D.H. Biesma
Dr. J. van der Net
Dr. K. Fischer
Chapter 1 Introduction 9
Chapter 2 Joint health and functional ability in children with 19
haemophilia who receive intensive replacement therapy
Development and preliminary testing of a paediatric 39
version of the Haemophilia Activities List (PedHAL)
Functional Limitations in Romanian children with 59
haemophilia: further testing of psychometric properties
of the Paediatric Haemophilia Activities List
Chapter 5 Habitual physical activity in Dutch children and 85
Adolescents with haemophilia
Chapter 6 Exercise interventions in patients with haemophilia: 103
a systematic review
Protected by nature? Effects of strenuous physical exercise 139
on FVIII activity in moderate and mild haemophilia
A patients: a pilot study
Chapter 8 Summary & General Discussion 153
Samenvatting (Dutch summary)
List of publications
Haemophilia is an X-linked inherited recessive bleeding disorder that is
characterized by a deficiency of clotting factor VIII (classic haemophilia, or
haemophilia A) or IX (haemophilia B). Haemophilia has a frequency of 1 in 5.000
male births, whereas haemophilia B has a frequency of 1 in 30.000 male births .
The level of clotting factor grades the severity of the disease. Patients with severe
haemophilia have <1% clotting factor activity, moderate affected patients 1-5%
and mild patients 6-40% . Lower levels of clotting factor, especially in the
severe patients result in spontaneous haemorrhages in muscles and joints, but may
affect other organs as well. Especially repetitive haemorrhages in joints ultimately
result in crippling haemophilic arthropathy . Patients with moderate haemophilia
may bleed into muscles and joints after minor injuries and mild haemophilia do not
bleed spontaneously, but only after medical surgery, dental extractions, or
With the development of cryoprecipitate in 1965 , correction of the
clotting factor deficit became possible. In the 1980s plasma derived clotting factor
concentrates have become available, and recombinant concentrates in the 1990s.
Although these new techniques have minimised the risk of blood-transmitted
infections such as Hepatitis C and HIV, the cost of concentrates has risen
enormously. This has increased the need for careful assessment of treatment
results. At first haemophilia was treated with intravenous administration of the
missing clotting factor at the occurrence of bleeding only. In the 1960s, professor
Inga Marie Nilsson  from Sweden started regular prophylactic replacement
therapy to prevent bleeding, followed by Professor Van Creveld in the early 1970s
 and others throughout Europe. In developed countries, early prophylactic
treatment has become the standard of care for patients with severe haemophilia.
This results in a significant reduction of the development of secondary arthropathy.
Decades of clinical experience and numerous retrospective and, recently,
prospective studies clearly demonstrate that prophylactic treatment is superior to
on-demand treatment, regardless whether the outcome is the number of joint- or
life-threatening bleeds, arthropathy evaluated by X-ray or MRI, or quality of life
Although the treatment of haemophilia has improved dramatically,
especially with the introduction of prophylaxis, still many patients around the
world are very much affected by the disease. One reason for this is that a large
majority (approximately 80%) of the patients live in developing countries where
financial constraints limit the use of factor concentrates . Another reason is the
formation of inhibitory antibodies (inhibitors) to factor concentrates in about 30%
of young patients with haemophilia A and in 1-6% of patients with haemophilia B
. When inhibitors are present, the treatment is less effective and patients may
be more affected by haemophilia in terms of joint status and quality of life .
Thus, despite improved treatment strategies, still many patients with haemophilia
experience the serious consequences of this disease.
Evaluation of functional health status in haemophilia
Evaluation of joint health in haemophilia has long been performed by using a
system based on consensus and developed by the World Federation of Haemophilia
(WFH) in the early 1980s . The WFH scoring system assesses aspects of joint
health including bleeding frequency, pain, and physical and radiological evaluation
(Pettersson score) . This WFH evaluation is still used to assess individual
patients and for research purposes, both in developed [14,15] and developing
countries . The WFH system, however, has two main shortcomings: lack of
psychometric properties (reliability, validity and sensitivity to change have never
been established) and its focus on pathology (bleeding frequency) and on body
functions and structures (radiological and physical evaluation, and pain). The WFH
evaluation does not assess activities, participation or contextual factors. Body
functions and structures reflect the function of organs and organ systems; they do
not necessarily predict the perception of a person’s functioning in daily life [17,18].
Healthcare workers are not just dealing with pathologies and their implications for
the body, but with the impact of these conditions on the person. This is particularly
the case with a disabling condition such as haemophilia .
The introduction of the International Classification of Functioning and
disability (ICF; Figure 1) by the World Health Organization has enabled a more
comprehensive evaluation of the functional health status. The model includes the
aspects of body functions and structures, activities and participation as well as
environmental and personal factors . During the past decade the ICF model has
been adopted widely and has become the preferred model for describing functional
health status in patients . Its adoption in haemophilia has been urged by De
Kleijn et al.  and has led to the development of several haemophilia specific
instruments for different levels/categories of the ICF. For example, on the level of
body functions and structures new tools have been developed to detect early
changes in joint structure such as Magnetic Resonance Imaging (e.g. [22,23]) and
the Haemophilia Joint Health Score (HJHS; [24,25]). On the level of activities both
a performance based (Functional Independence Score in Haemophilia; FISH,
[26,27]) and a self-reported outcome measure (Haemophilia Activities List; HAL;
[28,29]) have been developed. Both self-report and performance based measures
have showed to be necessary because of a low to moderate correlation between
these two and the need to report the efficiency and efficacy of physical activity
interventions [30,31]. For quality of life, as a summary measure, the disease-
specific Hemofilia-QoL  was developed for adults, and for children the
CHOKLAT and the Haemo-QoL [33,34]. A self-reported measure for functional
ability or activity level (according to the ICF) in children is lacking.
Figure 1: Interactions between the components of the ICF
Physical activity and haemophilia
An active lifestyle has numerous health benefits, especially for primary and
secondary prevention of chronic diseases (e.g., cardiovascular disease, diabetes,
cancer, hypertension, obesity, depression and osteoporosis) and premature death
. For patients with haemophilia physical activity even may have additional
benefits for musculoskeletal health including an increase in range of motion of the
joints , reduction of the number of joint bleeds  and improvement of
muscle strength and proprioception . Especially in areas where the supply of
factor concentrates is inadequate exercise interventions are generally considered
important, potentially effective and inexpensive options to treat patients with
haemophilia [39-42]. The need for a physical active lifestyle in patients with
haemophilia is further highlighted by the finding that bone mineral density in
children with severe haemophilia (FVIII/IX < 1%) is lower than in normal subjects
 and physical activity has shown to counteract this in healthy subjects .
Besides physical benefits, a physically active lifestyle may also contribute to
mental health . We underline the importance of psychosocial aspects in patients
with haemophilia, but to be able to have a more focussed approach this thesis
mainly deals with aspects of physical functioning.
Currently a positive trend is observed in which children with haemophilia
are increasingly encouraged to participate in physical activities and sports [45,46].
For example a survey in Dutch adults with haemophilia showed that of those that
are on prophylactic treatment a higher proportion than in the general population
was active in swimming and cycling . In addition, it was noted that the attitude
towards sports among patients with haemophilia has improved, and that the range
of practiced sports has increased, most likely due to improved medical treatment
. Despite the increased participation in sports, aerobic fitness of children with
haemophilia is still reduced compared to healthy peers , although it has greatly
improved when compared with the study of Koch et al.  that dates from 1986.
A recent study shows that engaging in vigorous activity increased the
number of bleeds of a trauma, while it did not increase the total number of bleeds
. More data are needed to determine the level of risk that is imposed on
children engaging in vigorous physical activity such as sports. Also the protective
effects of exercise are becoming clearer. For example, exercise could increase
muscles strength, which consequently could protect patients from bleeding
episodes . Furthermore acute bouts of exercise have shown to increase levels of
clotting factor in moderately affected patients . Although promising, these last
two studies included small samples and warrant further research.
Aims and outline of this thesis
It is clear that in haemophilia outcome measurement has long been strongly
focused on the level of body functions and structures and that functional outcome
and physical activity have been underrepresented. This results in little knowledge
about the functional consequences that haemophilia has in patients, both with or
without prophylaxis. This may be partly explained by a lack of disease specific
outcome measures that enable quantification of the limitation with regard to
performing functional activities.
The historic cautious attitude of health providers with regard to physical
activity may have led to a lack of knowledge in this area. With modern treatment
participation rate and levels of physical activity are changing and may positively
affect joint health and physical fitness; however it is not clear to what extent.
Furthermore, physical activity is increasingly advocated for haemophilic patients
both in developed and developing countries without attempts have been made to
systematically review and appraise the available literature on the effects of this
paradigm change. Also the acute effects of exercise on clotting factor levels in
patients with haemophilia are unclear.
Therefore, the aims of this thesis are:
To study the relationship between joint health and functional ability in
patients on intensive factor replacement therapy (chapter 2).
To develop and test an instrument to assess functional health status in
children with haemophilia (chapters 3&4).
To quantify habitual physical activity, including type and intensity, in
children and adolescents with haemophilia and its relationship with joint
health and physical fitness (chapter 5).
To study the current state of knowledge regarding exercise interventions in
patients with haemophilia (chapter 6).
To study the acute effects of vigorous physical activity on clotting factor
levels in patients with mild and moderate haemophilia A (chapter 7).
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