Joint Health, Functional Ability and Physical Activity in Haemophilia

184 Pages·2011·1.22 MB·English

Joint Health, Functional Ability and

Physical Activity in Haemophilia

Gewrichtsstatus, Functionele Mogelijkheden en Fysieke Activiteit
bij Patiënten met Hemofilie

door

Willem Gerardus Groen
Joint Health, Functional Ability and Physical Activity in Haemophilia
Thesis, Utrecht University, The Netherlands
ISBN-978-90-393-5688-3

© 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)

Proefschrift

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

door

Willem Gerardus Groen
geboren op 17 november 1981 te Hoorn
Promotoren:
Prof.dr. P.J.M. Helders
Prof.dr. D.H. Biesma

Co-promotoren:
Dr. J. van der Net
Dr. K. Fischer
Voor oma

Contents

Chapter 1 Introduction 9

Chapter 2 Joint health and functional ability in children with 19
haemophilia who receive intensive replacement therapy

Chapter 3 Development and preliminary testing of a paediatric 39
version of the Haemophilia Activities List (PedHAL)

Chapter 4 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

Chapter 7 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) 171
Dankwoord (Acknowledgements) 175
Curriculum Vitae 181
List of publications 183

Chapter 1

Introduction
Haemophilia
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 [1].
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% [2]. 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 [3]. 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
accidents [2].
With the development of cryoprecipitate in 1965 [4], 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 [5] from Sweden started regular prophylactic replacement
therapy to prevent bleeding, followed by Professor Van Creveld in the early 1970s
[6] 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
[7-9].
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
10