Hematology Conference - Bayer HealthCare

CONTENT
Conference Welcome Message 3
Agenda 4
Speaker Affiliation 6
Presentation Abstracts and Biographical Sketches 8
DISCLAIMERS | Some of the scientific presentations in this programme may discuss the use of agents or compounds that are investigational drugs and have not
yet received regulatory approval in some or all territories. The faculty, sponsor and organiser assume no responsibility for the unauthorised or unapproved use of
agents that may be discussed. The views expressed in this programme are not necessarily those of Bayer Schering Pharma.
DEAR COLLEAGUES,
On behalf of Bayer Schering Pharma, it is our pleasure to welcome you to Athens, Greece for the 2010 Hematology
Conference.
The Conference aims to offer an innovative and interactive approach using plenary sessions and state-of-the-art lectures,
which will focus on the continued efforts being made to improve the care given in the hemophilia community.
The Conference faculty comprises a group of internationally renowned experts who will present data, engage in
debate and lead interactive sessions in order to enhance all participants’ understanding of the importance of
providing optimal care; bearing in mind the famous quote that is highly relevant in hemophilia,
“Not life, but good life, is to be chiefly valued”, Socrates.
Many issues involved with hemophilia care will be investigated, including prophylaxis in children and adults, the
ageing person with hemophilia and sexual activity for people with hemophilia. There will also be a special lecture
discussing new findings in genetics and polymorphisms.
We are very excited to offer you what we feel is an interesting and stimulating program, which will be presented
through a mix of plenary sessions, discussions, interactive workshops and case studies. We strongly encourage you
to participate in the poster presentation session taking place during the Conference, and hope you will take the time
to review the display of research posters and ask the authors any questions you may have.
We look forward to meeting with you during the Conference, and hope that you commit to the discussions with the
same enthusiasm that we have felt whilst developing the program.
With best wishes,
CONFERENCE WELCOME MESSAGE
Erik Berntorp Flora Peyvandi Gertrud Schroeder
Conference Chair Conference co-Chair RBU Hematology/Neurology Europe
Bayer Schering Pharma AG
And the Steering Committee:
Jan Blatný (Czech Republic), Peter Collins (UK), Carmen Escuriola (Germany), Emna Gouider (Tunisia),
Cedric Hermans (Belgium), Helen Platokouki (Greece)
2 3

PROGRAM
THURSDAY, SEPTEMBER 30, 2010
Arrivals and country dinners
FRIDAY, OCTOBER 1, 2010
09:00 Introduction and Welcome
H. Duerr, E. Berntorp
09:15 Are Ethical Principles of Medical Care in Ancient Greece
Still Relevant Today?
E. Petridou
Session One
Prophylaxis: a Marathon, Not a Sprint
Session chairs: E. Berntorp, H. Platokouki
09:30 State-of-the-art Lectures
• History of Prophylaxis in Hemophilia
LM. Aledort
• The Start of the Run: Tunisia
E. Gouider
• Halfway Point: Czech Republic
J. Blatný
• The Finish Line: Sweden
J. Astermark
10:35 Current Practice and Outcomes
M. Carcao
11:05 Q&A and Panel Discussion
11:20 Coffee Break
11:50 Socio-Economic Aspects
• North American Perspective
A. Shapiro
• European Perspective
K. Steen Carlsson
→
→ 12:20 Practical Challenges
SATURDAY, OCTOBER 2, 2010
Session Four
• Venous Access
E. Santagostino
• Effective Communication, with and
Still in the Race
Session chairs: F. Peyvandi, C. Hermans
Education of, Family
K. Khair
09:00 The Aging Person with Hemophilia
• Setting the Scene
12:50 Q&A and Panel Discussion
G. Dolan
• Hypertension and Kidney Disease in Hemophilia
13:05 Lunch
P. de Moerloose
• Assessing Cardiovascular Risk
Special Lecture
C. Hermans
Introduction: F. Peyvandi
09:45 Q&A and Panel Discussion
14:35 New Findings in Genetics
T. Howard
10:00 Coffee Break
Session Two
Prophylaxis in Children and Adults
Session chairs: P. Collins, E. Gouider
15:05 Interactive Case Study Review and Discussion
16:20 Meeting Adjourns
E. Berntorp
Session Three
Poster Presentations
18:15 Meet in the Lobby for Departure from Hotel
19:10 Poster Presentations
20:30 Dinner
22:30 Departure to Hotel
Session Five
Breaking the Taboo
Session chairs: E. Berntorp, C. Escuriola
10:20 Sexual Activity and People with Hemophilia
• Interactive plenary session: The Perspectives
of a Urologist and a Sexologist
N. Bar-Charma, W. Gianotten
11:20 Late Breaking News: LIPLONG Results
• The first randomized, active controlled clinical trial to
investigate safety and efficacy of a long-acting FVIII product
J. Ingerslev
11:40 Poster Winners Presentation
J. Blatný
11:55 Examination and Meeting Close
E. Berntorp
12:15 Thank-You and Good-Bye
G. Schroeder
12:30 Lunch
4 5

SPEAKER AFFILIATION
Louis Aledort
The Mary Weinfeld Professor of Clinical Research in Hemophilia
Mount Sinai School of Medicine, USA
Jan Astermark
Centre for Thrombosis and Hemostasis
Malmö University Hospital, Sweden
Natan Bar-Chama
The Mount Sinai Medical Center, USA
Erik Berntorp
Malmö Centre for Thrombosis and Haemostasis
Skåne University Hospital, Sweden
Jan Blatny
Department of Hematology
University Hospital Brno and Masaryk University, Czech Republic
Manuel Carcao
The Hospital for Sick Children, Canada
Peter Collins
Department of Medical Genetics
Cardiff University School of Medicine, UK
Yesim Dargaud
Unité d'Hémostase Clinique
Hopital Edouard Herriot, Lyon, France
Philippe de Moerloose
The Haemostasis Unit
University Hospitals and Faculty of Medicine of Geneva, Switzerland
Roseline d'Oiron
Haematology Laboratory
Bicêtre Hospital AP-HP - Paris XI University, France
Gerry Dolan
Molecular Diagnostics Section
Nottingham University Hospitals, Queens Medical Centre, UK
Carmen Escuriola
Department of Haematology, Oncology and Haemostaseology
Johann Wolfgang Goethe University Hospital, Germany
Woet Gianotten
Medical Sexology
Rehabilitation Centre De Trappenberg, The Netherlands
Emna Gouider
Service d'Hématologie
Hôpital Aziza Othmana, Tunisia
Cedric Hermans
Haemostasis and Thrombosis Unit
St-Luc University Hospital, Belgium
Tom Howard
Department of Pathology and Laboratory Medicine
Veterans Affairs Greater Los Angeles Healthcare System, USA
Jorgen Ingerslev
Haemostasis and Thrombosis
Aarhus University Hospital Skejby, Denmark
Kate Khair
Department of Hematology
Great Ormond Street Hospital for Children NHS Trust, UK
Christine Loran
Department of Hematology
University Hospital of Wales, UK
Ramiro Núñez
Hematology Service
“Virgen del Rocio” University Hospital, Spain
Helen Pergantou
Haemophilia Centre-Haemostasis Unit
Aghia Sophia Children's Hospital, Greece
Eleni Petridou
First Department of Surgery
National and Kapodistrian University of Athens Medical School, Greece
Flora Peyvandi
Università degli Studi di Milano, Italy
Helen Platokouki
Haemophilia Centre-Haemostasis Unit
Aghia Sophia Children's Hospital, Greece
Elena Santagostino
Department of Medicine and Medical Specialties
A. Bianchi Bonomi Hemophilia and Thrombosis Center, Italy
Amy Shapiro
Department of Hematology
Indiana Hemophilia and Thrombosis Center, USA
Katarina Steen Carlsson
Department of Health Sciences
Malmö University Hospital, Sweden
Ondrej Zapletal
Centrum pro trombózu a hemostázu
Fakultní nemocnice Brno, Czech Republic
6 7

ARE ETHICAL PRINCIPLES OF MEDICAL CARE IN ANCIENT
GREECE STILL RELEVANT TODAY?
ELENI PETRIDOU
Dr Eleni Petridou, a Board Certified Pediatrician and Social Medicine Professional, is currently serving as a
Professor of Preventive Medicine and Epidemiology at Athens University Medical School. She is also the Director
of the Center for Research and Prevention of Injuries (CE.RE.PR.I.), and is President of the Hellenic Society for
Social Pediatrics and Health Promotion.
Dr Petridou is the past President of the European Society for Social Pediatrics, and is a member of the executive
board of the International Society for Violence and Injury Prevention (ISVIP). She has collaborated with the
Harvard Injury Control Research Center in the development, standardization and implementation of a screening
tool and educational package; for intimate partner violence in emergency departments and primary health care
settings in several European member states.
Dr Petridou has a wide experience in injury prevention and control pediatric and perinatal epidemiology; childhood
leukemia and lymphomas; cancer epidemiology; epidemiologic studies related to diet, tobacco, and alcohol
risk behavior; health services research and clinical epidemiology. She has published more than 250 research
papers and has received a series of awards for her work.
A R E E T H I C A L P R I N C I P L E S O F M E D I C A L C A R E I N A N C I E N T G R E E C E S T I L L
R E L E VA N T T O D AY ?
(IN COLLABORATION WITH TSIAMIS C, AND PANAGOPOULOU P.)
Ethical issues are an inextricable part of everyday medical practice and the Hippocratic Oath, along with related
documents, has been a beacon whenever faced with complex ethical concerns. However, the unprecedented
scientific advances in the delivery of contemporary medical care have generated a wide range of thorny
debates, as the decision making process often relies more on the availability of recent technological means, and
less on the personality and the competence of the treating physician. Hence, the applicability of Ancient Greek
deontological principles in Medicine might, at first glance, appear somehow shrinking.
Hemophilia, a genetically determined disorder with increased morbidity and mortality, seems to be a typical
medical condition for the prevention and treatment of which a spectrum of deontological controversies has
arisen. Actually, the ancient Greek principles of medical ethics governing patient-physician relations, accuracy
of diagnosis, responsibility of treatment and professional integrity are universal, and also apply to the medical
management of hemophilia, despite the fact that the condition had not been identified. Disease-specific ethical
issues in the contemporary era, for example, relate to: (a) equity in the provision of health care delivery to
hemophiliacs, given the high costs of prophylactic treatment, especially in less resourced settings or in periods
of financial crises; (b) risks and side effects associated with the implementation of advanced technologies in
the diagnosis and treatment; (c) respect for patients’ human rights in research projects involving children or
populations from developing countries; issues related to prenatal diagnosis and pregnancy interruption across
the globe; and (d) cost–effectiveness of recently available treatments, such as prophylactic administration
of Factor VIII, on the personal and the societal level, and even whether parameters such as “cost” should be
considered when a human life is at stake? Can the fundamental right to “the highest attainable standard of
health” be violated when states face financial crises?
It would be rather naïve to attempt to fully address such concerns in the complex, multi-cultural, multi-religious
and highly technologically dependent contemporary societies solely by trying to apply general Hippocratic
concepts, such as “help or at least do not harm”; core humanistic ancient Greek Medical Ethics, however, seem
to constitute the basic principles in this intricate quest.
8 9
NOTES
REFERENCES
• Lavery S, et al. Haemophilia. 2009; 144(30):303–307
• DiMichele D, et al. Haemophilia. 2006; 3:30–35
• DiMichele D, et al. Haemophilia. 2008; 3:122–129
• Street A, et al. Haemophilia. 2008; 3:181–187
• DiMichele D, et al. Haemophilia. 2003; 9(2):145–152
• Schaefer J, et al. Pediatr Nurs. 1999; 25(5):537–539
• Berntorp E, et al. Haemophilia. 2002; 8(3):435–438
• Shenfield F, et al. Haemophilia. 2002; 8(3):268–272
• Chandy M, et al. Haemophilia. 2002; 8(3):439–440

10
Socrates
Socrates (469BC – 399BC), credited as one of the founders of
Western philosophy, was a Classical Greek philosopher known
chiefly through the writings of his students and contemporaries;
Plato, Xenophon and Aristophanes
SESSION ONE
11

SESSION ONE
Prophylaxis: a Marathon, Not a Sprint
SESSION CHAIRS
ERIK BERNTORP
Dr Erik Berntorp is Professor at Malmö Centre for Thromboisis and Hemostasis, Lund University in Sweden.
His research interests include prophylactic treatment of hemophilia and of von Willebrand disease, genetic
aspects on inhibitor development and treatment of inhibitors in hemophilia including by-pass therapy and
immune tolerance induction. He is principal investigator for several multinational studies.
Dr Berntorp is a reviewer of numerous scientific journals such as Blood, Journal of Thrombosis and Haemostasis
and Haemophilia and has published more than 200 papers in peer-reviewed journals and has served
as editor for a number of major textbooks. He has served on the councils of World Federation of Hemophilia
and European Haematology Association.
HELEN PLATOKOUKI
Dr Helen Platokouki is a Pediatric Hematologist and the Director of the Hemophilia / Hemostasis Unit at the
“Aghia Sophia” Children’s Hospital in Athens, Greece. She obtained her Medical Degree at the University
of Athens Medical School, and gained her PhD at the Hemophilia/Hemostasis Unit and First Department of
Pediatrics, Medical School, University of Athens, Greece.
Dr Platokouki is a member of numerous national and international scientific societies. She is a board member
in the European Society of Pediatric Hematology and Oncology (ESPHI) and the Hellenic Society of Pediatric
Hematology-Oncology. She is the chair or a member in several working groups.
Dr Platokouki is the Principal Investigator or co-Investigator for a large number of national and international
multicenter studies, with a special focus in Idiopathic Thrombocytopenic Purpura (ITP), anticoagulation therapy,
prophylaxis and inhibitor management in hemophilia and on childhood thrombosis and rare bleeding disorders.
She is also the Principal Investigator for international multicenter studies in hemophilia therapies.
Her research interests include hemophilia inhibitor management, hemophilia prophylaxis and outcomes, CNS
thrombosis in neonates and children, ITP, quality of life in chronic patients. She is the author or co-author
of a great number of original articles, review articles and book chapters.
12 13
NOTES

SESSION ONE
Prophylaxis: a Marathon, Not a Sprint
THE HISTORY OF PROPHYLAxIS IN HEMOPHILIA
LOUIS ALEDORT
Dr Louis Aledort has been the Mary Weinfeld Professor of Clinical Research in Hemophilia at the Mount Sinai
School of Medicine in New York, USA since 1993. He joined the Mount Sinai School of Medicine in 1966, and was
the Scientist-in-Residence at the New School University.
Dr Aledort received his Doctor of Medicine in 1959 at the Albert Einstein College of Medicine, and in 1955 achieved
a Bachelor of Science in Chemistry at Queens College of the City of New York.
Dr Aledort has been a member of the Practice Committee of the American College of Physicians since 2001.
In 2002 he became a member of the editorial board for two prestigious publications; Journal of Thrombosis and
Haemostasis and American Journal of Hematology. Since 1968, Dr Aledort has been a professional member of
the American Society of Hematology, the New York Society for the Study of Blood and the International Society
of Hematology.
In 2010, Dr Aledort received a Lifetime Achievement Award from the Hemophilia and Thrombosis Research
Society (HTRS).
T H E H I S T O R Y O F P R O P H Y L A x I S I N H E M O P H I L I A
Mild hemophilia inspired two Swedish investigators to conceive of and initiate the concept of prophylaxis.
Trying to change the phenotype of severe patients led the way to programs of maintaining patients in a mild
state. This concept took years to be disseminated, adopted, and adapted. The QoL ability to participate as more
normal people at a higher cost dovetailed with the advent of self-infusion and concentrate availability. Issues
that arose were compliance, venous access, ports, infection, thrombosis, when to start, is it forever, and what
of those who exposed and have joint disease.
These issues have led to prospective studies to determine optimal regimens, primary versus secondary prophylaxis,
how critical are trough levels, can one define early joint damage as something to prevent, and can joint progression
in adults be moderated.
Although prophylaxis can prevent joint disease, many PWH go without any therapy. Many unresolved issues
regarding prophylaxis remain and will be addressed.
REFERENCES
• Aledort LM, et al. J Intern Med. 1994; 236:391–399
• Carcao MD, et al. Blood Reviews. 2004; 18:101–113
• Collins PW, et al. A. J Thromb Haemost. 2009; 7:413–420
• Manco-Johnson MJ, et al. N Engl J Med. 2007; 357:535–544
14 15
NOTES

SESSION ONE
Prophylaxis: a Marathon, Not a Sprint
THE START OF THE RUN: TUNISIA
E M N A G O U I D E R
After graduate studies at the University of Medicine in Tunis, Dr Emna Gouider specialized in hematology, and
then joined the University career. She is currently a Professor of Biological Hematology and a member of the
Tunisian Society of Hematology.
Dr Gouider is responsible for the hemophilia treatment center in Tunis, where more than 300 patients with
bleeding disorders are assisted. She was appointed General Director of the National Blood Transfusion Center
in Tunisia.
Involved for years in the Tunisian Association as member responsible for medical and scientific affairs,
Dr Gouider was elected Chairperson.
THE START OF THE RUN: TUNISIA
Prophylaxis is the standard of care in severe hemophilia, but economic conditions limit its practice. In Tunisia,
a developing country, clotting factor concentrate is now available for on demand therapy (0.3UI/capita in 2007
and 0.64UI/capita in 2009). In order to stop or prevent arthropathy, which concerns about 40% of patients, we
decided to introduce gradual prophylaxis. Since some patients have a weekly consumption of substitution, we
aim to start prophylaxis with the equivalent amount of clotting factor concentrate consumption. Started in 2007,
prophylaxis with low doses of clotting factor concentrates was initially prescribed for patients who bleed at least
once a month or who have target joint. Doses and frequency of replacement therapy are adapted if necessary
according to a tailored schema, in order to optimize cost effectiveness regimen. Prophylaxis was started with
10 UI/kg twice a week; if this is not sufficient we move to 10UI/kg three times per week or 20 UI/kg twice a week,
for A patients. A once weekly 20UI/kg dose is used for hemophilia B patients, if insufficient we move to 20UI/kg
weekly or 10UI/kg twice a week. A control of inhibitors is performed every 20 injections.
To date, 9 patients have needed dose-escalation in the initial schema, and we have observed less or no joint
bleeds in most patients, especially those who started prophylaxis early. No patient has developed new synovitis.
All patients had a better quality of life. No patients have developed inhibitors.
Our conclusion is that prophylaxis should be generalized, progressively, to all patients in our country as early
as possible.
REFERENCES
• Steen Carlson K, et al. Haemophilia. 2003;9:555–566
• Risebrough N, et al. Haemophilia. 2008; 14:743–752
• Fischer K, et al. Haemophilia. 2002;8:745–752
• Manco-Johnson M, et al. N Engl J Med. 2007;357:535–44
• Schramm W and Berger K. Haemophilia. 2003;9(suppl 1):11–115
• Aronstam A, et al. J Clin Path. 1977;30:65–67
• Hoots K and Nugent D. Thromb and Haemost. 2006;96:433–440
• Aronstam A, et al. Br J Haematol. 1976;33(1):81–90.
16
• Feldman B, et al. Haemophilia.2007;13:745–749
• Feldman BM, et al. J Throm Haemost. 2006;4:1228–36
17
NOTES

SESSION ONE
Prophylaxis: a Marathon, Not a Sprint
HALFWAY POINT: CzECH REPUBLIC
J A N B L AT N ý
Dr Jan Blatný is currently a Consultant Hematologist and the Lead Clinician at the Department of Clinical Hematology
& Centre for Thrombosis and Hemostasis at the Children’s University Hospital Brno, Czech Republic. The
center includes one of two pediatric comprehensive hemophilia care centers in the country and is a tertiary
referral center for coagulation disorders in pediatrics for a 4 million population (approx). He is also actively
involved in a pediatric leukemia and cancer program provided by Children’s University Hospital Brno.
Dr Blatný received his MD from Masaryk University, Czech Republic in 1994, and following a residency in the
Pediatric, Hematology and Oncology Divisions at the Children’s University Hospital Brno, Czech Republic,
he went on to complete post-doctoral fellowships at the University Maternity Hospital in Brno. In 2005, he
completed his PhD dissertation, Risk factors of severe complications associated with central venous lines in
children treated for malignant disease – prediction in risk analysis.
From September 2006 till June 2008 Dr Jan Blatný worked as Consultant Hematologist at the Temple Street
Children’s University Hospital in Dublin, Ireland, specializing in Pediatric Hematology for the Children’s University
Hospital, Rotunda Maternity Hospital and Our Lady’s Children’s Hospital, where he is involved also in
the program of Hemophilia CCC. His main fields of interest were always Hemophilia, life threatening bleeding
and thrombosis in children.
Dr Blatný cooperates with the Perinatal/Pediatric Scientific and Standardization Committee (SSC) of the
International Society on Thrombosis and Haemostasis (ISTH) and serves on the Working Group on Pediatric
Hematology of the Czech Pediatric Society. He is also a member of the World Federation of Haemophilia,
American Hematology Society, Czech Society of Hematology and the Czech Society on Gastroenterology. He
is one of the supervisors and administrators of the world-wide ISTH endorsed pediatric registry, focused on
life-threatening bleeding: SeveN BleeP. Dr Blatný is a lecturer on Pediatric Hematology at Masaryk University,
Brno and has authored and contributed to many articles and books.
HALFWAY POINT: THE CzECH REPUBLIC
In the Marathon, as in any race, it is not enough to just start the run. You have to have enough strength throughout
the whole race, and you should not stop half way! The same is true for the development of hemophilia care.
Twenty-two years ago in the former Czechoslovakia, the run for hemophilia was more than difficult. The ‘iron
curtain’ was shut and uncrossable, making it almost impossible to obtain factor concentrates from the world
behind it. Patients with hemophilia were only treated with FFP or Cryoprecipitate, and the total consump-
tion of FVIII/year/capita was far below 1 IU. There were no home treatments available and no prophylaxis,
despite the fact that the benefit of both had been well known for more than twenty years at that time
(1,2)! Insufficient treatment led to the devastation of locomotory apparatus in numerous patients. In fact,
the treatment was limited to in-patients interventions in the case of significant bleeds only. This situation
was frustrating for both patients and caregivers. However, after the political change, known also as the
‘Velvet Revolution’, the run could finally go on!
The Czech Republic is home to over 10 million people, approximately 800 of which have hemophilia, and
a quarter of them are children under 18 years of age. Once the factor concentrates became available for
Czech patients, we started to use them for appropriate and efficient treatment “on-demand”, as well as
for short term secondary prophylaxis. This made it possible to set up an ambitious program for surgical
interventions (including total hip replacements) in patients who suffered from multiple target joints due
to previous inadequate treatment of their disease. Based on the recommendations of WFH, the building
up of the network of hemophilia centers had been initiated. Home treatment was introduced, and within
several years it became available for all who needed and wanted it.
Due to improved hemophilia care, as well as the remarkably improved availability of clotting factor concentrates,
we were able to introduce secondary prophylaxis for children born during the late nineties. It was
a major change in hemophilia care for the country! At the time we had chosen a similar approach to the
Dutch regimen (3), which gave us an opportunity to offer such a treatment to all children at an affordable
cost. We also started the national-wide program of summer camps for children with bleeding disorders,
which became an integral part of hemophilia care and further promoted home treatment, self-application
and prophylaxis within the Czech hemophilia population.
Currently consumption of FVIII is 3,6 IU/year/capita in the Czech Republic. All our children are offered primary
prophylaxis, which must start within the first 2 years, and not later than after the first bleed. Prophylaxis
is started gradually with escalating frequency, based on the individual bleeding pattern, to reach final
median dose of 24IU/kg; the factor three times a week in hemophilia A and twice a week in hemophilia B.
We seldom use CVDs (Central Venous Devices) in our patients as they are often able to cope well with the
treatment via peripheral veins. On this treatment, our boys with severe hemophilia bleed only 4 times/year
in median (national-wide registry HemIS, 2008 data). Our data thus supports the evidence that prophylaxis
has an undoubted benefit for children with hemophilia (4).
The only positive consequence of the ‘iron curtain’ in the past was the low number of people with hemophilia
infected with HIV (around 30, including 7 children). But this benefit was countered by the total isolation of
the country from the rest of the world which is, of course, indefensible in any way! Despite the fact that
few Czech people with hemophilia were endangered by blood born diseases in the past, we always aimed
for the safest treatment for our patients. The vast majority of them are currently treated with high purity
plasma derived concentrates, but the number of recombinant products is constantly increasing. Since 2006,
all newly born children with hemophilia are commenced on recombinant products, as well as minimally
treated and previously untreated pediatric patients. The switch to recombinant factor concentrates is
also offered to other eligible pediatric patients. However, the final decision must always be the consensus
between the hemophilia treater, patient and their family! The national-wide strategy of hemophilia care is
firmly anchored within the Czech National Hemophilia Program – the multidisciplinary body which unites
all of the Czech hemophilia treatment centers. A similar approach is also endorsed by the Working Group
on Pediatric Hematology of the Czech Hematology and the Czech Pediatric Societies. The Czech Republic
participates in many international projects focused on hemophilia care (e.g. EUHASS, ESChQoL etc…)
18 19

SESSION ONE
Prophylaxis: a Marathon, Not a Sprint
HALFWAY POINT: CzECH REPUBLIC
Despite the progressive introduction of recombinant products, our inhibitor rate remains low (incidence of clinically
significant inhibitors 6% and total incidence 14% in pediatric population). We believe that these findings
are in accord with the results of the CANAL study (5). Perhaps the fact that we start prophylaxis gradually may
play a certain role, as recently published by Kurnik and co-workers (6). Though it might be just the speculation,
it seems to be more important “how you treat” your patient than “what you treat him with”?!
On the other hand, the inhibitor has been and probably will always be a well-known complication of hemophilia
treatment. Thus we have to be able to offer adequate treatment to all patients, who develop it. In the
Czech Republic, ITI is the treatment of choice for children with inhibitors. Adult patients with inhibitors are
mostly treated on demand with by-passing agents, and ITI is used seldom. When using ITI we follow current
international experts’ consensus (7).
Although “half of the run” is already behind us, there is still a lot to do. We promised to ourselves, as well as
to our patients, that we would complete the marathon run; the torch has been lit and shall never go out!
R E F E R E N C E S
1. Berntorp E, et al. Haemophilia. 2003;9(Suppl 1):1–4
2. Nilsson IM, et al. Bibl Haematol. 1970;34:111–24
3. Fischer K, et al. Haemophilia. 2002;8:753–760
4. Manco-Johnson MJ, et al. New Engl J Med. 2007;357:535–544
5. Gouw SC, et al. Blood. 2007;109:4648–54
6. Kurnik K, et al. Haemophilia. 2010;16:256–262
7. Dimichele DM, et al. Haemophilia. 2007;13(Suppl 1):1–22
20 21
NOTES

SESSION ONE
Prophylaxis: a Marathon, Not a Sprint
THE FINISH LINE: SWEDEN
JAN ASTERMARK
Dr Jan Astermark is an Associate Professor at the Centre for Thrombosis and Hemostasis at the Skane University
Hospital in Malmö, Sweden. He is the co-editor of the International Monitor on Hemophilia, and currently serves
as an Executive Committee member of the European Association of Haemophilia and Allied Disorders (EAHAD)
and the Nordic Haemophilia Council.
Dr Astermark is a reviewer for several hematology journals, and has published a number of original articles,
review articles and book chapters in the field of hemophilia and coagulation disorders. He serves as the Principal
Investigator for large international multicenter studies with a special focus on inhibitor development in
hemophilia.
THE FINISH LINE: SWEDEN
Prophylactic treatment reaching a trough level of the deficient factor above 1 IU/dL was initiated on a small
scale in Sweden in the late 1950s, when the observation was made that patients with moderate disease did not
suffer from as many bleeds and had fewer affected joints than patients with severe disease. In this way, Swedish
patients with hemophilia became pioneers in the area of prophylaxis, and through the years have shown improved
clinical outcome and health status. Today, treatment is begun as primary prophylaxis before the age of 2 years
and preferentially before the onset of joint bleeds. The initial dosing is generally 25 IU/kg once weekly, gradually
escalated on an individual basis to every second day in patients with hemophilia A and 2-3 times weekly
in hemophilia B. In most cases infusions are made in a peripheral vein, but in the event this poses problems, a
central line, e.g. a Port-A-Cath, can be inserted. Based on experience from studies of pharmacokinetic dosing, daily
prophylaxis has also been evaluated. This mode of treatment has the potential to provide improved protection
against bleeds as well as lower consumption of factor concentrates. The primary obstacles to daily treatment
are convenience and compliance, but for some patients this method is actually quite attractive, and becomes
a natural part of daily living. This demonstrates that treatment should be individualized, not only on the basis
of the bleeding phenotype, but also on the preferences and inclinations of the patient. In recent years, data
suggesting that early prophylaxis may prevent the development of inhibitory antibodies through avoidance of
treatment in association with danger signals have been accumulating. Whether this is indeed the case must be
confirmed, but the finding further supports the initiation of early primary prophylaxis, the use of which has been
State-of-the-Art for many years. Currently there is a debate surrounding the optimal time to stop prophylaxis.
Hemophilia is a life-long disease with ongoing factor deficiency and risk of severe bleeds. Thus, from a logical
point of view, treatment should not be postponed or stopped, but continued into adulthood. This is also common
practise in Sweden. An important task for the future will be to increase the cost-effectiveness of treatment with
improved modalities. The new long-acting molecules of the future will potentially be important additives. With
the individualized use of these, prophylaxis will be further optimized from both a clinical and a cost perspective,
and used throughout the entire lifespan.
22 23
NOTES
R E F E R E N C E S
• Nilsson IM, et al. J Intern Med. 1992;232(1):25–32
• Astermark J, et al. Br J Haematol. 1999;105(4):1109–13.
• Kurnik K, et al. Haemophilia. 2010;16(2):256–62. Epub 2009 Oct 29

SESSION ONE
Prophylaxis: a Marathon, Not a Sprint
CURRENT PRACTICE AND OUTCOMES
MANUEL D. CARCAO
Dr Manuel D. Carcao received his medical training from the University of Toronto, Canada, graduating in 1990. In
2007 he received a Masters of Science degree in Clinical Epidemiology at the same institution. He is currently
a staff pediatric hematologist/oncologist in the Division of Hematology/Oncology and an Associate Professor
in the Department of Pediatrics at The Hospital for Sick Children in Toronto. Dr Carcao is also Co-Director of
the Comprehensive Care Pediatric Hemophilia Clinic and is an Associate Scientist/Clinician Investigator in the
hospital’s research institute – the Division of Child Health Evaluative Sciences.
Dr. Carcao’s research interest is in the study of congenital bleeding disorders (hemophilia, VWD and rare inherited
coagulation and platelet disorders) and in particular the study of inter-patient disease variability with respect
to inhibitor development, prophylaxis needs and pharmacokinetics.
Dr. Carcao was the President of the Association of Hemophilia Clinic Directors of Canada from 2006 to 2008. He
is on the Board of Directors of the Hemophilia and Thrombosis Research Society of North America (2010-13). He
is an active member of the International Prophylaxis Study Group (IPSG) serving in various capacities: member
of the “Outcomes working group” and Co-Chair of the “Prophylaxis in inhibitor patients working group”.
Dr Carcao is on the editorial board of several well known journals. He has been an invited lecturer on many
occasions, and is the author or co-author of numerous peer-reviewed papers.
CURRENT PRACTICE AND OUTCOMES
Patients with severe hemophilia experience recurrent bleeds, particularly into joints, and can develop painful and
disabling arthropathy [1]. Prophylaxis, defined as the regular infusion of clotting factor concentrates in order to
prevent bleeding, has been shown in cohort studies [2-6] and in a prospective randomized study [7] to greatly
improve musculoskeletal outcomes and quality of life of patients with severe hemophilia.
In addition to all the known benefits of prophylaxis (less joint bleeding, less life threatening bleeds, better
joint outcomes, improved quality of life, increased participation in physical activities including sports) another
recently discovered benefit of prophylaxis, if started early, is that prophylaxis appears to reduce the risk of
inhibitor development in patients with severe hemophilia A.
Yet despite the myriad benefits of prophylaxis most of the world’s population of severe hemophilia patients
is not on prophylaxis mainly due to the high cost of prophylaxis which is attributed almost exclusively to the
cost of factor concentrates. Hence many investigators are looking at whether prophylaxis can be made less
expensive while still retaining much, if not all, of the benefits of prophylaxis.
Often prophylaxis has been thought as an all or none phenomenon; either a patient is on a “standard” prophylaxis
regimen which in many countries tends to be the full dose regimen developed in Sweden or a patient is not on
prophylaxis. Yet investigators in the Netherlands, Canada and various countries have shown that many patients
do very well with much less intense prophylaxis regimens [3, 8, 9]. This is likely attributed to the phenotypic
heterogeneity that exists among patients with severe hemophilia. Furthermore even within patients prophylaxis
needs may vary over time [8].
Less intense prophylaxis regimens likely come with less need for central venous access devices, less cost and
better compliance. This is particularly the case when commencing very young children on prophylaxis.
Most studies that compare the cost of treating patients on prophylaxis to the costs of treating patients on
demand have generally found that prophylaxis is three times more expensive than on demand therapy mainly
because patients on prophylaxis use three times more factor than patients treated on demand. Yet it is becoming
appreciated that prophylaxis can be provided in much more cost-effective ways. Investigators are just now
beginning to explore prophylaxis regimens involving daily infusions of small doses of factor (given first thing in
the day). Considerable cost savings might be achieved with such regimens while at the same time maintaining
the benefits of prophylaxis.
How to get prophylaxis more widely available for the vast majority of the world’s population of hemophilia
patients remains a key goal for the 21 st century. Regimens that use factor in a more cost-effective manner need
to be explored to bring the benefits of prophylaxis to much of the world’s population of hemophiliacs which
have so far not had access to prophylaxis.
REFERENCES
1. Ahlberg A, et al. Acta Orthopaediatr Scand. 1965; 77:3–132
2. Nilsson IM, et al. J Int Med. 1992; 232:25–32
3. Fischer K, et al. Haemophilia. 2002; 8:745–52
4. Aledort LM, et al. J Intern Med. 1994; 236:391–9
5. Liesner RJ, et al. Br J Haematol. 1996; 92:973–8
6. Smith PS, et al. J Pediatr. 1996; 129:424–31
7. Manco-Johnson MJ, et al. N Engl J Med. 2007; 357:603–5
8. van den Berg HM, et al. Br J Haematol. 2001; 112:561–5
9. Feldman BM, et al. J Thromb Haemost. 2006; 4:1228–36
24 25
NOTES

SESSION ONE
Prophylaxis: a Marathon, Not a Sprint
SOCIO-ECONOMICS ASPECTS: NORTH AMERICAN PERSPECTIVE
AMY SHAPIRO
Dr Amy Shapiro is the Medical Director of the Indiana Hemophilia and Thrombosis Center and the adjunct Professor
of Pediatrics at the Michigan State University, USA. She has also been appointed to the National Hemophilia
Foundation’s Medical and Scientific Advisory Council, and is active on the National Institutes of Health Clinical
Trial Review Board, and Data and Safety Monitoring Boards for both Gene Therapy and Transfusion Medicine
and Hemostasis.
Dr Shapiro received her medical training at New York University School of Medicine, New York, USA, and completed
her pediatric internship, residency and fellowship in pediatric hematology/oncology at the University of Colorado
Health Sciences Center. Before taking up her current position, she was Associate Professor of Pediatrics at the
Indiana University School of Medicine.
Dr Shapiro is very active in improving treatment for people with bleeding disorders in Indiana and has received
numerous awards for her work including the W George Pinnell Award for Outstanding Service and the Distinguished
Hoosier Award in 2009 from the State of Indiana. In 2001, she was voted the National Hemophilia Foundation
Physician of the Year. She has also authored or co-authored over 120 papers and abstracts and eight textbook
chapters. Dr Shapiro belongs to numerous professional societies including the World Federation of Hemophilia,
the International Society on Thrombosis and Haemostasis and the American Society of Hematology. She is
past-president of the American Thrombosis and Hemostasis Network.
S O C I O - E C O N O M I C S A S P E C T S : N O R T H A M E R I C A N P E R S P E C T I V E
The impact of hemophilia is clinically evident through progressive arthropathy, the hallmark disease associated
sequela. Prophylaxis has been proven to improve musculoskeletal outcomes in patients with severe hemophilia.
Decreased bleeding rates due to use of prophylactic regimens have allowed patients to achieve a near normal
lifespan and lead life styles that are often indistinguishable from the unaffected population. The overall
societal and personal gain achieved by prophylaxis can be measured in part through an individual’s ability to
participate in age relevant activities and overall function; examples of these activities and outcomes include
school attendance, academic achievement and eventual gainful employment. In addition, health related quality
of life is improved through prophylaxis yet is also dependent upon the rigor of and adherence to the regimen
utilized, the need for central venous catheters, and the rate of breakthrough bleeding, and subsequent target
joint development. Prophylaxis, although clearly the preferred treatment modality to achieve optimal outcome,
is not universally utilized even in countries whose economies can support use of this regimen. Prophylactic
regimens confer significant medical costs that include, but are not limited to, the cost of clotting factor
concentrate, hospitalizations, required surgical interventions, emergency room visits, etc. These direct costs
must be weighed against the costs of lost productivity and progressive arthropathy when on-demand regimens
are utilized. The socio-economic aspects of prophylaxis may be viewed from either the individuals or overall
societal perspective and likely differ based upon the age of the patient population. Existing data, although limited,
is available on the socio-economic aspects of prophylaxis in the Pediatric population; data specific to the adult
population is more limited. As prophylactic regimens have gained acceptance, a population of patients with
improved outcomes have entered adolescence and early adulthood. Follow-up of these populations including
evaluation of the continuation and utility of prophylaxis and its social-economic impact will provide increasing
data pertinent to adult population.
The use of prophylaxis in North American countries will be reviewed and specific data from the Universal
Data Collection (UDC) Study presented. These data demonstrate that overall in the United States 53% of the
participating population of severe hemophilia A patients of all ages utilized a prophylactic regimen. Data
pertaining to the social and economic impact of prophylaxis in both pediatric and adult populations pertinent
to the North American prospective will be presented.
REFERENCES
• Coppola A, et al. Thromb Haemost. 2009; 101(4):674–81
• Von Mackensen S, et al. Haemophilia. 2007; 13(2):38–43
• Shapiro AD, et al. Pediatrics. 2001; 108(6):E105
• Nicholson A, et al. Haemophilia. 2008; 14(1):127–32
• Naraine VS, et al. Haemophilia. 2002; 8(2):112–20
• Salk L, et al. Soc Sci Med. 1972; 6(4):491–505
• Carcao M, et al. Haemophilia. 2010; 16(2):4–9
26 27
NOTES
• Rentz A, et al. Haemophilia. 2009; 15(5):1039–47
• Walsh CE, et al. Haemophilia. 2009; 15(5):1014–21
• Risebrough N, et al. Haemophilia. 2008; 14(4):743–52
• Tencer T, et al. Haemophilia. 2007; 13(5):480–8
• Feldman BM, et al. Haemophilia. 2007; 13(6):745–9
• Ota S, et al. Haemophilia. 2007; 13(1):12–20
• Butler RB, et al. Haemophilia. 2003; 9(5):549–54

SESSION ONE
Prophylaxis: a Marathon, Not a Sprint
SOCIO-ECONOMIC ASPECTS: EUROPEAN PERSPECTIVE
K ATA R I N A S T E E N C A R L S S O N
Dr Steen Carlsson earned her PhD in economics in 1999 at Lund University, Sweden. She is currently a postdoctoral
research fellow in health economics at Lund University and a research director at the Swedish Institute
for Health Economics, IHE, Lund, Sweden. Her research includes empirical economic analyses and evaluations of
medical technology and health interventions. She is first author of three peer-reviewed publications evaluating
prophylactic and on-demand treatment for severe hemophilia and one peer-reviewed cost-effectiveness analysis
of bypassing agents for treatment patients with hemophilia who have developed inhibitors.
Recent and on-going research includes analyses of registry data on long-term disease (hemophilia, diabetes,
psoriasis) and disability (personal assistance, adults with multiple functional limitations). Dr Steen Carlsson
is appointed health economist to National Guidelines for Diabetes Care at the National Board of Health and
Welfare in Sweden.
SOCIO-ECONOMIC ASPECTS: THE EUROPEAN PERSPECTIVE
A life-long disease such as hemophilia has an impact on the daily life for the patient and also for the family.
Before the introduction of replacement treatment with factor concentrates, persons with severe hemophilia could
not expect to reach adulthood. The median length of life has been estimated to about 20 years [1]. Replacement
treatment, and especially prophylactic treatment strategies, has changed the prospects in terms of length of
life and of quality of life [2-4]. In addition, it has expanded the individual’s range of choices, i.e. increased both
the possibilities of participating in the labor market and the range of possible professions. Previous findings
have shown that patients with severe hemophilia on long-term prophylactic treatment starting early in life were
more likely to be active on the labor market compared to patients with on-demand treatment [4].
This presentation will present new results based on data on long-term socio-economic outcomes of high-dose
and intermediate dose prophylaxis using longitudinal data on patients with severe hemophilia born from 1970
and later in the Netherlands and in Sweden. Intermediate dose prophylaxis has been available for patients in
the Netherlands since the 1970s and high-dose prophylaxis for patients in Sweden. This presently provides up to
40 years follow-up of the long-term consequences of alternative prophylactic treatment strategies. The results
include analyses of self-assessed quality of life and labor-market participation. The findings will also be related
to the societal context in respective countries.
28
REFERENCES
1. Larsson SA, et al. Br J Haematol. 1985; 59:593-602
2. Darby SC, et al. Blood. 2007; 110: 815-25
3. Miners AH, et al. Haemophilia. 1999; 5:378-85
4. Steen Carlsson K, et al. Haemophilia. 2003; 9: 555-66
29
NOTES

SESSION ONE
Prophylaxis: a Marathon, Not a Sprint
PRACTICAL CHALLENGES: VENOUS ACCESS
ELENA SANTAGOSTINO
Dr Elena Santagostino is a contract Professor in the School of Clinical and Experimental Hematology at the
University of Milan / IRCCS Maggiore Hospital, working closely with Professor Mannucci. After graduating in
Medicine from the University of Milan, Dr Santagostino completed a PhD at Maastricht University focusing on
the safety of hemophilia treatment and its complications.
Recipient of the ISTH Young Investigators Merit Award in 1991, Dr Santagostino also received an award for
research in the hemophilia field (Italian Society of Hemostasis and Thrombosis, 2000) and the ‘Special Project
Award’ - Bayer Hemophilia Awards Program Grant - at the 2003 ISTH Congress. In addition to these awards,
Dr Santagostino has authored over 90 original articles and more than 400 abstracts.
P R A C T I C A L C H A L L E N G E S : V E N O U S A C C E S S
Modern treatment for hemophilic children is based on prophylaxis and immune tolerance induction (ITI). Both
treatment regimens are based on frequent infusions at early ages, therefore an adequate venous access is
essential. Peripheral veins represent the best option, however, different solutions, as central venous access devices
(CVADs) and arteriovenous fistulae (AVFs), can be adopted if needed. CVADs have been used in hemophiliacs,
however their survival is affected by infectious complications. Among CVADs, fully implantable devices are usually
preferred to external lines due to a lower infectious risk. The limited survival of CVADs may have a relevant impact
on treatment outcome, especially in case of ITI where treatment interruptions are counterproductive.
To overcome such drawbacks, internal AVF has been considered as an alternative option owing to a lower rate
of infectious complications. Moreover, AVF is easy to use in the home setting and well accepted by children.
Possible complications not preventing AVF use are postoperative hematoma and transient symptoms of distal
ischemia; one case of symptomatic thrombosis has been reported so far. Long-term complications include loss
of patency, aneurysmatic dilatation and, rarely, limb dysmetria and a regular follow-up is mandatory to allow
early remedial intervention. Surgical dismantlement of AVF is recommended as soon as transition to peripheral
veins is possible.
REFERENCES
• Santagostino E, et al. Blood Transfus. 2008; 6(s2):12–16
• Berntorp E, et al. Bull World Health Organ. 1995;73:691–701
• http://www.hemophilia.org/NHFWeb/Resource/StaticPages/
mmuO/menu5/menu57/170.pdf.
• http://www.wfh.Org/2/docs/Publications/Diagnosis_and_
Treatment/Guidelines_Mng_Hemophilia.pdf.
• Manco-Johnson MJ, et al. N Engl J Med. 2007; 357:535–44
• DiMichele DM, et al. Haemophilia. 2007; 13(suppl 1):1–22
• Valentino LA, et al. Haemophilia. 2004;10:134–46
• Santagostino E, et al. Br J Haematol. 2003; 123:502–6
• McCarthy WJ, et al. J Vase Surg. 2007; 45:986–91
• Santagostino E, et al. J Thromb Haemost. 2007;
5(suppl 2):OS-061
• Petiini P, et al. Haemophilia. 2003; 9(suppl 1):83–7
• Feldman BM, et al. J Throm Haemost. 2006; 4:1228–36
• Bollard CM, et al. Haemophilia. 2000; 6:66–70
• Fontes B, et al. Int Surg. 1992; 77:118–21
30 31
NOTES

SESSION ONE
Prophylaxis: a Marathon, Not a Sprint
EFFECTIVE COMMUNICATION WITH, AND EDUCATION OF, FAMILY
KATE KHAIR
Since becoming a state registered nurse in 1981, Kate Khair has gained a number of other professional qualifications
including State Registration in Pediatric Nursing, a Masters Degree in Anthropology, a City and Guilds Masters
Degree in higher levels of practice, and several modules in Advanced Nursing.
Kate has worked in hemophilia at Great Ormond Street Hospital for Children in London since 1991 and in
2003 became a nurse consultant. She is currently working towards a PhD on the experience of children
with hemophilia, which is funded through a 2008 Bayer Caregivers Education Award with the University of
Greenwich in London.
In 2010 Kate was elected to the Nurses Committee of the World Federation of Hemophilia, and looks forward
to expanding the work already undertaken by this group of dedicated nurses; to promote the best care and
practice for nurses and patients worldwide.
EFFECTIVE COMMUNICATION WITH, AND EDUCATION OF, FAMILY
Hemophilia is a lifelong disorder which necessitates life long education and support. This presentation will
address both the educational and support needs of newly diagnosed children and their families, and will
demonstrate how age and development appropriate education can be utilized to support individual patients/
families through the life stages into adulthood (1).
The roles of health care providers in supporting patients along this continuum of learning will be demonstrated (2).
Emphasis will be on the benefits of education today to prevent health issues of the future.
New and innovative models of communication and education, for example by ‘expert patient peers’ will also
be discussed.
REFERENCES
1. Lindvall K, et al. Haemophilia. 2006; 12(1):47–51
2. Nazzaro et al. Am J Public health. 2006; 96: 1618–1622
32 33
NOTES

SESSION ONE
Prophylaxis: a Marathon, Not a Sprint
SPECIAL LECTURE: NEW FINDINGS IN GENETICS
TOM HOWARD
Dr Tom Howard is a Pathologist in the Department of Pathology and Laboratory Medicine for the Veterans
Affairs Great Los Angeles Healthcare System (VAGLAHS), California. His other clinical appointments at VAGLAHS
include being the Director of the Special Hemostasis Laboratory and the Director of the Pharmacogenetics
Section, Molecular Laboratory.
Dr Howard is also an Associate Professor (in residence) in the Division of Hematology and Oncology at the
David Geffen School of Medicine, UCLA. His other primary academic appointment is as an Associate Professor
of the Department of Pathology and Laboratory Medicine at the Keck School of Medicine, USC.
Dr Howard graduated in 1986 from the University of California, Los Angeles with a Bachelor of Science in
Biochemistry (Departmental Honors). He reviews manuscripts for various publications, including Thrombosis
and Haemostasis and Haemophilia.
Dr Howard is an active member of many societies, including the American Society of Hematology and the
International Society of Thrombosis and Hemostasis.
NEW FINDINGS IN GENETICS
Infusion of factor VIII (FVIII) concentrates has allowed successful management of patients with hemophilia A
during the past half-century. The effectiveness of this strategy is offset by the development of alloantibodies,
termed “inhibitors”, which neutralize the activity of the wild-type FVIII replacement protein. Inhibitors develop
in 20% or more of patients with severe hemophilia A. Although clinical strategies for the management of
patients with inhibitory FVIII antibodies have improved, these interventions are extremely expensive and not
always successful. In addition, alloimmunized patients experience high levels of morbidity and mortality, and
a poor quality of life.
Studies carried out over the last two decades have greatly expanded our understanding of the factors that
contribute to the development of inhibitors in hemophilia A patients or, in other words, to the immunogenicity of
the wild-type FVIII protein(s) in replacement products. Inhibitor pathogenesis is complex and involves numerous
product and patient related factors. Relatively little attention, however, has been given to the potential effect of
nonsynonymous (ns)-single-nucleotide polymorphisms (SNPs) — slight differences in the human FVIII gene (F8)
which code for single amino acid substitutions that do not cause hemophilia A but create structurally distinct
wild-type FVIII proteins — on the development of this adverse alloimmune treatment outcome. I will discuss
our recent studies demonstrating racial differences in the distribution of ns-SNPs in F8 and how these could
contribute to the variable incidence of inhibitor development observed in different populations.
I will also discuss the HLA class II genes and their ns-SNPs, as these loci encode the patients’ MHC-based antigen
presentation repertoire for exogenous peptides and thus determine whether a given individual with any given
F8 mutation type and collection of F8 ns-SNPs will or will not be able to mount an immune response to one
or more existing (or future pipeline) FVIII replacement molecules. Finally, I will describe how knowledge of all
this information in conjunction is necessary for the development and validation of predictive strategies that
enable us to establish alternative personalized approaches for replacement, immune-tolerance induction, and
(ultimately) curative gene-based therapies.
34 35
NOTES
REFERENCES
1. Mannucci PM, et al. New England Journal of Medicine. 2001; 344:1773-1779
2. Dasgupta S, et al. Immunology Letters. 2007; 110:23–28
3. Ehrenforth S, et al. Lancet. 1992; 339:594-598
4. de Biasi R, et al. Thrombosis and Haemostasis. 1994; 71:544–547
5. Gringeri A, et al. Blood. 2003; 102:2358-2363
6. Lacroix-Desmazes S, et al. Blood. 2008; 112:240-249
7. Astermark J. Haemophilia. 2006; 12(3):52-60
8. Schwaab R, et al. Thrombosis and Haemostasis. 1995; 74:1402-1406
9. Frazer KA, et al. Nature. 2007; 449:851-861
10. Viel KR, et al. Blood. 2007; 109:3713-3724
11. Viel KR, et al. New England Journal of Medicine. 2009; 360:1618-1627
12. Kemball-Cook G, et al. Nucleic Acids Research. 1998; 26:216-219
13. Ettinger RA, et al. Blood. 2009; 114:1423-1428
14. Shina T, et al. Journal of Human Genetics. 2009; 54(1):15-39
15. Bogunovic B, et al. PLoS ONE. 2010; 5(5)1-10
16. Yewdell JW, et al. Annual Review of Immunology. 1999; 17: 51-88
17. Wang P, et al. PLoS Computational Biology. 2008; 4(4):e1000048

36
Socrates’ Life
In Xenophon’s work Symposium, Socrates is reported to have
devoted himself only to what he regards as the most important
occupation: discussing philosophy.
SESSION TWO
37

SESSION TWO
Prophylaxis in Children and Adults
SESSION CHAIRS
PETER COLLINS
Dr Peter Collins is a reader in hematology at Cardiff University, and is an Honorary Consultant Hematologist and
Director of the Arthur Bloom Hemophilia Centre at the University Hospital of Wales, Cardiff.
Dr Collins is the Chair of the UKHCDO Inhibitor Working Party and Pharmacokinetic subgroup of the International
Prophylaxis Study Group. His research interests include von Willebrand disease, acquired hemophilia, prophylactic
treatment in hemophilia and acquired hemostatic failure.
EMNA GOUIDER
For biography please see page 16.
38 39
NOTES

SESSION TWO
Prophylaxis in Children and Adults
INTERACTIVE CASE STUDY REVIEW AND DISCUSSION
O N D R E J z A P L E TA L
Dr Ondrej Zapletal has been a Consultant Hematologist in the Department of Clinical Hematology, Thrombosis
and Hemostasis Center at the University Hospital Brno, Czech Republic since 2006. He joined the University
Hospital Brno in 1999, where is worked on the Department of Pediatric Oncology for three years, before
become a Registrar in the Department of Clinical Hematology.
Dr Zapletal graduated in 1999 with a Masters Degree in General Medicine from Palacký University in Olomouc,
Czech Republic. He went on to specialize in General Pediatrics, and obtained a 2nd Degree in 2005 before
focusing on Hematology and Transfusion Medicine. Since 2005, he has been a PhD student at the Masaryk
University in Brno, Czech Republic.
CARMEN ESCURIOLA ETTINGSHAUSEN
Dr Carmen Escuriola has been a member of the Department of Pediatric Hematology and Oncology at the
Children’s Hospital of the Johann Wolfgang Goethe-University in Frankfurt since 1993. She also works in the
Department of Pediatrics at the Comprehensive Care Centre for Thrombosis and Hemostasis at the University
Hospital of Frankfurt.
Dr Escuriola completed her study of medicine at the University of Frankfurt in 1993. She is a member of the
German, Swiss and Austrian Society for Thrombosis and Hemostasis Research (GTH) and the International
Society for Thrombosis and Hemostasis (ISTH).
Dr Escuriola’s research fields include Hemorrhagic disorders, particularly in the treatment of hemophiliacs
and hemophiliacs with inhibitors.
YESIM DARGAUD
Dr Yesim Dargaud is currently an Associate Professor in the University of Lyon and a consultant hematologist
in the Clinical Hemostasis Unit lead by Prof C Négrier. She completed her medical studies in the University of
Lyon, France. In 2002, Dr Dargaud obtained a Master’s degree in Biology and Pharmacology of Hemostasis and
Vessel Walls from the University of Paris-VII. After completing training in Laboratory Medicine, she obtained
an MD at the University of St. Etienne in 2004. In 2005, Dr Dargaud obtained a diploma in complementary
specialized studies in Hematology from the University of Lyon. She was later admitted to the programme to
prepare a specialization in Vascular Medicine – Angiology at the University of Lyon.
In 2006, Dr Dargaud obtained a PhD degree at the University of Lyon. She trained under the supervision of Prof.
HC Hemker and Prof S Béguin on the biochemistry of thrombin generation, in the University of Maastricht in
2003. In 2005, she moved to the Cambridge University teaching hospital to work with Dr. T. Baglin on platelet
dependent thrombin generation. Recently, she worked on the cell based model of thrombin generation at
the University of North Carolina in Chapel Hill with Prof DM Monroe and Prof M Hoffman.
Dr Dargaud’s special research interests include inherited bleeding disorders, hemophilia with inhibitor and
bypassing therapies. She received a Bayer Hemophilia Clinical Scholarship Award (2004), a Bayer Hemophilia
Early Career Investigator Award (2007), a NovoNordisk Poster Award (2007), a CSL Behring - Prof Heimburger
Award (2008) and a Gold Medal degree in medicine (Lyon University Teaching Hospitals, 2004-05). She is (co)
author of 40 articles and several communications on subjects in hemostasis and thrombosis.
PETER COLLINS
For biography please see page 38.
RAMIRO NúñEz VázqUEz
Dr Ramiro Núñez Vázquez has worked in the Hemophilia Unit of Virgen del Rocío Hospital in Seville, Spain
since 2003. He first became a Resident in the Hematology Service of the Virgen del Rocío Hospital in 1996,
after graduating at the University of Seville, Spain.
Dr Núñez Vázquez is a member of the Medical College of Seville, the Spanish Society of Thrombosis and
Hemostasis and of the Spanish Working Group on the Prevention and Treatment of Hemorrhages in Hemophilic
Patients with Inhibitors.
40 41

SESSION TWO
Prophylaxis in Children and Adults
INTERACTIVE CASE STUDY REVIEW AND DISCUSSION
H E L E N P E R G A N T O U
Dr Helen Pergantou is a Consultant in the Hemophilia Center/Hemostasis Unit at the “Aghia Sophia” Children’s
Hospital in Athens, Greece. She received her medical degree at the Medical School of National University in
Athens in 1989 and in 2007 received a PhD degree at the Hemophilia Center/Hemostasis Unit and 2nd department
of Pediatrics at the University of Athens and “Aghia Sophia” Children’s Hospital.
From 1992-1997, Dr Pergantou trained in Pediatrics at the “Aglaia Kyriakou” Pediatric Hospital and in 1997
began training in Emergency Care at their Pediatric Intensive Care Unit.
Since 1998, Dr Pergantou’s speciality has been in hemophilia and related coagulation disorders. Her research
interests include hemophilia and related musculoskeletal issues, inhibitor development in patients with
congenital factor deficiencies, rare bleeding disorders, the role of hemostasis in critically ill patients, and
the thrombosis in neonates and children.
She is the co-investigator in various national and international multicenter studies and is also the author
and co-author of many original articles in international journals.
ELENA SANTAGOSTINO
For biography please see page 30.
C H R I S T I N E L O R A N
Christine qualified as a Registered Nurse in 1983, and started her career in General Medicine for two and a half
years. In 1986, she commenced a period in hematology as part of the newly opened Bone Marrow Transplant
Unit at University Hospital of Wales, Cardiff, where she spent six years as Senior Staff Nurse.
Christine moved to the Hemophilia Center in 1992 as a part time Staff Nurse whilst her children were young.
She took a brief break after the birth of her son before returning in 1997, when Dr Peter Collins had taken
over as Director of the Arthur Bloom Hemophilia Center. She became the Clinical Nurse Manager of the
Haemophilia Center in 2001, which remains her current role. In 2005, she completed the MSc in Nursing
Science at Cardiff University, Cardiff.
Christine’s special interest is in prophylaxis, for persons with severe hemophilia, and in particular how it can
improve their quality of life.
GERRY DOLAN
For biography please see page 2.
42 43

44
Socrates and the Oracle at Delphi
In Plato’s work Apology, the Oracle at Delphi stated that none
were wiser than Socrates. Socrates, believing that he did not
possess any wisdom, proceeded to test the statement by
questioning the prominent wise-men of Athens. He concluded
that man knew very little and was not wise at all. Therefore the
Oracle was correct. Socrates wisdom was demonstrated by his
awareness of his own ignorance.
SESSION THREE
45

SESSION THREE
POSTER PRESENTATIONS
BASIC RESEARCH AND DEVELOPMENT
01 The International Database on Rare Bleeding Disorders (RBDD): 67 novel
mutations and recurrent genetic variants
Andrea Cairo
02 Frequency of haplotype H1 and H2 among Tunisian hemophiliac patients
Emna Gouider
03 An assessment of childhood hemophilic arthropathy in Hungary
Maria Kardos
04 Molecular mechanisms of haemophilia A responsible of large duplication in
xq28 locus: New insights provided CGH array
Nathalie Lannoy
05 Thrombin Generation Test (TGT): could it be a good tool to follow the
coagulation potential of a severe haemophilia A child with inhibitors?
Phu-Quoc Lê
06 An innovative approach of functional assessment of haemophilic arthropathy
by three-dimensional gait analysis
Sébastien Lobet
07 The European Network of Rare Bleeding Disorders (EN-RBD) project:
results of 3-years analysis
Marzia Menegatti
08 The role of ultrasonography in mild arthropathy of haemophilic children
Diana Molnar
09 Assessment of bone density and strength using peripheral
quantitative computed tomography (pqCT) in children with
haemophilia - preliminary report
Panagiota Xafaki
TREATMENT AND CARE
10 Antiplatelet therapy in patients with haemophilia and von Willebrand disease
Rosa Sonja Alesci
11 Clinical experience with prophylaxis - new findings
Günter Auerswald
12 Inhibitor generation during continuous infusion of factor
concentrates in patients with haemophilia A, -B and
von Willebrand disease undergoing surgery
Günter Auerswald
13 Describing occurrence and treatment of ischemic heart disease in
haemophilia: an Italian retrospective study
Antonio Coppola
14 Rare bleeding disorders identified at routine pre-operative screening in
children: Report of two cases
Marina Economou
15 The role of social networking in haemophilia management
Kate Khair
16 Mild Haemophilia in Sweden
Eva Mattsson
17 Multiple serous, muscular and subcutaneus hemorrhages in a
patient with hemophilia A
Elina Tsvetelinova Peteva
18 First toe phalanx amputation because of vasculopathy after the orthopedic
surgery in severe hemophiliac patient: Case report
Ilgen Sasmaz
CHALLENGES IN HEMOPHILIA CARE
19 LINx © : an educational project for children, parents and caregivers in order to
optimize the care of hemophilia.
Phu-Quoc Lê
20 qoL in adult patients with haemophilia
Karin Lindvall
21 Venous access in children with hemophilia: the use of arteriovenous fistula
Maria Elisa Mancuso
22 The European Network of Rare Bleeding Disorders (EN-RBD) project:
the bleeding score (BS)
Roberta Palla
23 Clinical characteristic of children with congenital coagulation disorders
from north-east Bulgaria
Elina Tsvetelinova Peteva
24 Central nervous system (CNS) bleeding in patients with rare
bleeding disorders (RBDs)
Simona Maria Siboni
25 Management of haemophilia in the emergency department
Annarita Tagliaferri
BAYER SCHERING PHARMA POSTERS
26 Cost of inhibitor development in patients with severe haemophilia A in Spain
Óscar Montejo, Laia Febrer
27 www.hemophiliasource.info
Roswita Neumann, Tricia Lata Gooljarsingh
28 Bayer Schering Pharma: Overview on Research & Development
activities in hemophilia
no author
INVITED POSTERS
29 Variations in international practices for the peri-operative management of
major surgery for persons with severe hemophilia
Pal Andre Holme
30 Inhibitor Eradication Practices in Adult Patients – Results of a Global Survey
Geraldine Lavigne
31 International Survey of laboratory tests used in the diagnosis
and evaluation of Hemophilia A
Keith Gomez
01 02 03 04 05 06 07 08 09 10
46 47
21
11 12 13 14 15 16 17 18 19 20
22 23 24 25 26 27 28 39 30
31

48
Socrates' Knowledge
One of the best known sayings of Socrates is “I only know that
I know nothing”, remarking that his wisdom was limited to an
awareness of his own ignorance.
SESSION FOUR
49

SESSION FOUR
Still in the Race
SESSION CHAIRS
FLORA PEYVANDI
Dr Flora Peyvandi is an Associate Professor of Internal Medicine at the Angelo Bianchi Bonomi Hemophilia
and Thrombosis Center at the University of Milan, Italy.
In 1991, Dr Peyvandi obtained a Medical Degree at the University of Milan, and in 1996 specialized in hematology.
Between 1996 and 1998, she worked in London, UK on a research project on the molecular characterization of
FVII and FX deficiency as a first step of her PhD thesis. To further characterize the molecular alterations she
found in London, Dr Peyvandi moved to the Veteran Administration Hospital at Harvard University, Boston
where she studied the mechanisms causing FVII deficiency using the molecular and cell culture technique.
In May 1999 she came back to the Angelo Bianchi Bonomi Center, University of Milan, Ospedale Maggiore to
finish her PhD studies on the rare bleeding disorders, and to continue a new line of research on molecular
and cell biology studies on the serine proteases of coagulation. In 2001 she received a PhD doctorate in “Rare
bleeding disorders” at the University of Maastricht, Holland.
Since 2001, Dr Peyvandi has been working in the Department of Internal Medicine and Hematology, IRCCS
Maggiore Hospital, Mangiagalli and Regina Elena Foundation, which cooperates with the University of Milan.
She is responsible for the hematology outpatient clinic for hemophilia, rare bleeding disorders, hemorrhagic
and thrombotic diseases, reproductive assistance to HIV discordant couples and prenatal diagnosis. In 2005
she became an Associate Professor in Internal Medicine.
CEDRIC HERMANS
For biography please see page 56.
50 51
NOTES

SESSION FOUR
Still in the Race
THE AGING PERSON WITH HEMOPHILIA: SETTING THE SCENE
G E R R Y D O L A N
Dr Gerry Dolan has been a Consultant Hematologist since 1991 and is the Lead for Hemostasis and Thrombosis
at Nottingham University Hospitals, in Nottingham, UK. He is also the Hemophilia Director of the Nottingham
Comprehensive Care Center.
Dr Dolan received his medical degree from Glasgow University Medical School. He held training posts in internal
medicine and hematology in Glasgow, Edinburgh, and Sheffield. His research interests include the molecular
aspects of inherited bleeding disorders, ageing and hemophilia and outcome measures of hemophilia care.
Dr Dolan is the Chairman of the European Hemophilia Therapy Standardization Board and the Chairman of the
ADVANCE group. He is the current Vice-Chairman of the UK Hemophilia Center Doctors’ Organisation (UKHCDO).
He is also Chairman of the UKHCDO Data Management Working Party and a member of the UKHCDO Working
Parties on Transfusion-Transmitted Infection and Genetics. Dr Dolan is the Past President of the British Society
for Haemostasis and Thrombosis.
THE AGING PERSON WITH HEMOPHILIA: SETTING THE SCENE
Life expectancy has increased for persons with hemophilia. In the early part of the last century, the prevalence
of hemophilia was estimated to be only 4 per 100,000 males, while the prevalence in the 1990s was estimated
to be 13-18 per 100,000 (1). More recent studies estimating life expectancy for individuals with severe hemophilia
not infected with HIV in the period 1977 – 2001 have ranged from 63 years for the UK, to 70 years (Netherlands)
and 73 years (Canada) (2, 3, 4). There are as yet no clear estimates of how rapidly this population will grow but
Rosendaal and colleagues estimated that the numbers of severe hemophiliacs would increase by approximately
20% within two generations (1) and the general consensus is that life expectancy is approaching that of the
general population.
Historically, the clinical management of hemophilia has been dominated by the risk of bleeding, the risk of chronic
arthropathy and of transfusion-transmitted infection and most comprehensive care programs for hemophilia
have been shaped by these medical issues (5). Improvements in care such as the availability of safe, effective
factor concentrate and the adoption of prophylaxis have greatly reduced or eliminated these concerns. However,
the risk of disease increases with age and it is likely that we will see many more individuals developing chronic
illness that may have a complex interaction with their bleeding disorder. It has been estimated that 77% of
individuals over the age of 65 have 2 or more chronic illnesses (6) and it is likely that older individuals with
hemophilia will experience a similar pattern of health issues.
Cardiovascular disease, including ischemic heart disease, hypertension and renal disease are leading causes
of morbidity and mortality in older individuals. As individuals with hemophilia age, it is likely that many more
individuals with these conditions will be seen. (7,8) It is important that proper screening and preventative medical
interventions are introduced to the comprehensive care of individuals with hemophilia and this may necessitate
a review of Comprehensive Care programs.
REFERENCES
1. Rosendaal FR, et al. Annals of Hematology. 1991; 62:5–15
2. Darby SC, et al. Blood. 2007; 110:815–825
3. Plug I, et al. Journal of Thrombosis & Haemostasis.2006; 4(3):510–6
4. Walker IR, et al. Haemophilia. 1998; 4:714–720
5. Colvin BT, et al. Haemophilia. 2008; 14:361–374
6. Anderson G, et al. Public Health Reports. 2004; 119(3):263–270
7. Tuinenburg A, et al. Journal of Thrombosis and Haemostasis. 2009; 7:247–254
8. Lambing A, et al. Haemophilia.2009; 15:33–42
52 53
NOTES

SESSION FOUR
Still in the Race
THE AGING PERSON WITH HEMOPHILIA: HYPERTENSION AND KIDNEY DISEASE IN HEMOPHILIA
PHILIPPE DE MOERLOOSE
Pr Philippe de Moerloose is a Professor in the Department of Internal Medicine, Head of the Hemostasis Unit
and Adjunct Chef de Service for the Division of Angiology and Hemostasis at the University Hospital in Geneva
Switzerland. He holds specialist training degrees in Internal Medicine, Angiology and Hematology.
Pr de Moerloose has served in numerous official capacities at the local, national and international level, including
the International Society of Thrombosis and Haemostasis and the World Haemophilia Society. He is a member
of the Executive Committee and Advisory Board for numerous international hemophilia, hemostasis and/or
thrombosis congresses. He will organise the next European Association for Haemophilia and Allied Disorders
(EAHAD) Congress in 2011 in Geneva.
Pr de Moerloose serves on the editorial or advisory board of a number of medical journals. In particular he is
Associate Editor of the Journal of Thrombosis and Haemostasis. In addition, he has authored or co-authored
over 300 peer-reviewed publications, review articles and book chapters.
T H E A G I N G P E R S O N W I T H H E M O P H I L I A : H Y P E R T E N S I O N A N D K I D N E Y
DISEASE IN HEMOPHILIA
Do persons with hemophilia (PWH) have more hypertension than the general population? And what about
kidney disease, particularly what is the role of hematuria? And is there a relationship between kidney disease
and hypertension?
Concerning the first question (PWH and hypertension), many studies suggest that for more than 30 years PWH
have more hypertension than the general population. Indeed in 1977, J. Weisz and C. Kasper (1) reported an
increased prevalence (33%) of hypertension in 233 PWH. No differences in the lifetime exposure to blood products
of all types were found in normotensive and hypertensive patients. In 1990 Rosendaal et al (2) confirmed that
PWH had, on average, higher blood pressures than the comparison population and used hypertensive drugs
twice as often. No association was found between the severity of hypertension and blood pressure. In both
studies hypertension was mainly due to a higher mean of diastolic blood pressure. In a cohort of Canadian
patients with mild hemophilia, 29% were hypertensive compared to 18% of the control subjects (3). Many
confounding factors have to be taken into account in these retrospective analysis but Siboni et al (4) still
found an increased prevalence of hypertension in severe PWH after adjusting for alcohol intake, use of pain
killers and anti-HIV medication.
Hematuria is common among PWH, but its long-term effects on renal function are not well-defined. In addition
infection with HIV and hepatitis C, exposure to nephrotoxic agents (e.g. HAART), the presence of an inhibitor or
the use of tranexamic acid may place PWH at increased risk for renal disease. In 1970, Prentice et al (5) found a
large number of renal complications in PWH. Kulkarni et al (6) analyzed data collected from 3,422 PWH in six US
states and found that acute and chronic renal diseases were strongly associated (among other factors) with
hypertension.
These data imply that blood pressure and renal monitoring should be carefully followed in PWH. At the present
time it is difficult to see a clear relationship between hypertension and renal disease (influence of hypertension
on renal disease and vice versa) and to establish the role of kidney bleeds. A questionnaire (H3 for Hemophilia,
Hypertension and Hematuria) will be sent to ADVANCE members to compile epidemiological data on the link
between hemophilia, hypertension and hematuria, in order to help generate data that will contribute to the
development of guidance on the management of adult PWH.
REFERENCES
1. Weisz J, et al. DHEW publication, NIH. 1977; 77-1089:103–9
2. Rosendaal, et al. Br J Haematol. 1990;75:525–30
3. Walsh M, et al. J Thromb Haemsot. 2008;6:755–61
4. Siboni S, et al. J Thromb Haemost. 2009;7:780–6
5. Prentice, et al. Q J Med. 1971;40:47–61
6. Kulkarni, et al. Haemophilia. 2003;9:703–10
54 55
NOTES

SESSION FOUR
Still in the Race
THE AGING PERSON WITH HEMOPHILIA: ASSESSING CARDIOVASCULAR RISK
C E D R I C H E R M A N S
Dr Cedric Hermans completed his medical training and specialization in General Internal Medicine at the
school of Saint-Luc University Hospital of the Catholic University of Louvain, Belgium. He obtained his PhD
in Biomedical Sciences, specializing in Toxicology, in 1999.
In 2000 Dr Hermans took up a one year fellowship in the Hemophilia Center and Hemostasis Unit of the Royal
Free Hospital, London. He was appointed Associate Professor at the Medical School of the Catholic University
of Louvain in 2003 and Clinical Professor in 2009. He is currently heading the Division of Hematology and the
Hemostasis and Thrombosis Unit of the Saint-Luc University Hospital of the Catholic University of Louvain,
Brussels.
Dr Hermans has published over 90 articles in international journals and is a member of several scientific
societies. Presently, his main research interests lie in the area of hemostasis and thrombosis, especially
clinical studies on the treatment of hemophilia, new anticoagulants, and the management of thrombosis
and inherited bleeding disorders.
THE AGING PERSON WITH HEMOPHILIA: ASSESSING CARDIOVASCULAR RISK
Individuals with hemophilia have long been considered to be protected from cardiovascular disease and
mortality. This assumption is supported by the lower cardiovascular mortality documented in different previous
cohort studies, suggesting a cardiovascular protective effect of lifelong low coagulation factor levels.
With longer life expectancy in patients with hemophilia, diseases associated with ageing, such as cardiovascular
disease, are increasing in importance. With respect to the cardiovascular risk factors, an increased
prevalence of hypertension and lower mean total cholesterol levels compared to the general population
were found about 20 years ago by Rosendaal and colleagues who assessed the prevalence of cardiovascular
risk factors in 95 hemophilia patients.
In the absence of more recent and extensive study, one can assume that the cardiovascular risk profile of
patients with hemophilia has changed over the last decades as a result of ageing, change in the pattern of
comorbidities, and the adoption by most patients of the western lifestyle. In addition, one cannot rule out
that the wider use of prophylaxis could to some extent mitigate the vascular protection on atherothrombosis
provided by the hypocoagulability secondary to haemophilia. In this context, there is a clear need for large
studies evaluating the prevalence of cardiovascular risk factors in adult and elderly patients with haemophilia.
Prevention of coronary heart disease in clinical practice is based on the assessment of the individual's total
burden of risk using the prevalence of multiple concurrent risk factors (Score). This risk algorithm has never
56 57
NOTES
been validated in the hemophilia population. It therefore appears premature to use this tool to estimate the
expected cardiovascular mortality in patients with hemophilia. Despite these limitations, active screening
for cardiovascular risk factors should be encouraged in all patients with hemophilia. Hypertension and
hyperglycemia should be carefully screened for, not only because they increase the risk for cardiovascular
events, but also because they enhance the risk of microvascular disease and cerebral haemorrhage for which
hemophilia has no preventive effect.
REFERENCES
• Franchini M, et al. Clin Inten/Aging 2007:2:361–368
• Miesbach W, et al. Haemophilia 2009;15:894–899
• Siboni SM, et al. Thromb Haem 2009;7;780–786
• Dolan G, et al. Haemophilia 2009;15(Suppl 1):20–27
• Mauser-Bunschoten EP, et al. Haemophilia 2009:15:853–863
• Rodendaal FR, et al. Br J Haematol 1989;71:71–6
• Darby SC. Blood 2007;110:815–25
• Plug I et al. J Thromb Haemost 2006;4:510–6

58
Socratic Method
Perhaps one of Socrates most important contributions to West-
ern philosophy was his dialectic method of inquiry, known as
the Socratic Method. In order to solve a problem, it is broken
down into a series of questions, the answers to which would
gradually reveal the answer
SESSION FIVE
59

SESSION FIVE
Breaking the Taboo
SESSION CHAIRS
ERIK BERNTORP
For biography please see page 12.
CARMEN ESCURIOLA ETTINGSHAUSEN
For biography please see page 40.
60 61
NOTES

SESSION FIVE
Breaking the Taboo
SExUAL ACTIVITY AND PEOPLE WITH HEMOPHILIA
NATAN BAR-CHAMA
Dr Natan Bar-Chama is the Director of the Center of Male Reproductive Health at RMA in New York. He is a board
certified urologist who received his medical degree with special distinction for research in male infertility, and
also completed his urology residency at the Albert Einstein College of Medicine. In 1993, Dr Bar-Chama was
awarded the prestigious New York Academy of Medicine F.C. Valentine Fellowship and received sub-specialty
training in male reproductive medicine and surgery at the Baylor College of Medicine in Houston, Texas.
Dr Bar-Chama is the Director of Male Reproductive Medicine and Surgery, and an Associate Professor in the
Departments of Urology, Obstetrics, Gynecology and Reproductive Sciences at the Mount Sinai School of Medicine.
His subspecialty clinical practice is exclusively dedicated to male reproductive medicine and microsurgical
reconstruction for the treatment of male-factor infertility (vasectomy reversal, varicocelectomy, testicular and
epididymal sperm retrieval, and vasectomy).
Dr Bar-Chama's research and publications have focused on male infertility and erectile dysfunction. In 1998,
he received the Pfizer Scholars in Urology Award for leadership, innovation, and outstanding achievement in
urological science. Since 2005, Dr Bar-Chama has been listed each year as one of the "Best Doctors in New York"
by New York Magazine. Dr Bar-Chama serves on the Board of Directors for the Society for Male Reproduction
and Urology (SMRU), of the American Urological Association (AUA) (to be president in 2012), The Society of Male
Reproductive Urology (SMRU) of the American Society of Reproductive Medicine (ASRM) and The American
Fertility Association.
S E x U A L A C T I V I T Y A N D P E O P L E W I T H H E M O P H I L I A : T H E P E R S P E C T I V E S O F A
UROLOGIST AND A SExOLOGIST
Sexual dysfunction is common in aging men and may be exacerbated by the special medical issues and psychological
problems associated with hemophilia. Sexual healthcare for men with hemophilia (MWH) requires a background
understanding of common patterns of sexual function and dysfunction in the aging male, of expectable sexual
complications of hemophilia and related co-morbidities, and of sexual aspects of psychological issues. A sexual
history differentiates problems involving a loss of sexual desire from ejaculatory difficulties and erectile dysfunction
(ED), distinguishes organic from psychogenic ED, and guides further evaluation. Physicians treating MWH
should be familiar with the use of phosphodieterase-5 inhibitors as first-line treatment for ED and recognize the
need for referral to specialized sexual urology and mental health professionals when appropriate. As increasing
numbers of MWH reach middle age and beyond, many experience problems with sexual function, including loss
of sexual desire, ejaculatory difficulties, and varying degrees of erectile dysfunction. Some of these conditions
are caused by age-related biological changes in the hormones, nerves, and blood vessels responsible for male
sexual function. Other sexual difficulties are specific to the medical problems associated with hemophilia, such
as chronic pain, bleeding, infection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV), and
sexual side effects of medications. Finally, some sexual problems result from the psychological experience of
living with hemophilia. For example, the burdens of medical illness, caretaking, and shame and embarrassment
about having HCV and/or HIV may compromise sexual relationships and cause men to worry about being desirable
to potential partners. Sexuality can be a valuable source of meaning, self-esteem, and fulfilment, and its
importance to individuals with chronic illness and their partners should not be underestimated. Sexuality can
also be a window into other significant health issues. Healthcare providers can do much to help MWH remain
sexual. However, integration of sexual healthcare into the busy routine of office/clinic practice is not easy.
Sexual healthcare for MWH requires a background understanding of common patterns of sexual function and
dysfunction in the aging male, of expectable sexual complications of hemophilia and related co-morbidities, and
of sexual aspects of psychological issues. Effective sexual history-taking identifies the kind of sexual disorder
and directs further evaluation. When ED is diagnosed, PDE-5 inhibitors are first-line therapy. If sexual difficulties
persist with treatment, referral to sexual specialists in urology and mental health care is indicated.
REFERENCES
• O'Donnell AB, et al. Exp Gerontol. 2004; 39:975–84
• Harvard Medical School. Harvard Men's Health Watch. 2009; 13:1–4
• NIH Consensus Conference. JAMA. 1993; 270: 83–90
• Rosenberg MT, et al. Int J Clin Pract. 2007; 61:1198–208
• Aversa A, et al. Int J Urol. 2010; 17:38–47
• Gianotten WL, et al. Haemophilia. 2009; 15:55–62
• Daniell HW, et al. J Pain. 2002; 3:377–84
• Collazos J, et al. AIDS Rev. 2007; 9:237–45
• Kraus MR, et al. J Endocrinol. 2005; 185:345–52
• Danoff A, et al. Am J Gastroenterol. 2006; 101:1235–43
• Dove LM, et al. Gastroenterology. 2009; 137:873–84
• Wylie K, et al. Maturitas. 2010; 65:23–7
• Schweitzer I, et al. Aust N Z J Psychiatry. 2009; 43:795–808
• Fazio L, et al. CMAJ. 2004; 170:1429–37
• Lue TF, et al. N Engl J Med. 2000; 342:1802–13
• Sullivan ME, et al. BJU Int. 2001; 87:838–45
62 63
NOTES

SESSION FIVE
Breaking the Taboo
SExUAL ACTIVITY AND PEOPLE WITH HEMOPHILIA
WOET GIANOTTEN
Dr Woet Gianotten graduated as an MD in the Netherlands. His spent the first part of his career concentrating
on tropical medicine, with training in surgery, gynacology and obstetrics and over five years working in various
places in West and East Africa.
Back in the Netherlands Dr Gianotten settled in two areas; he engaged in the contraceptive aspects of reproductive
health care, and the other was in sexology. He was trained as a psychotherapist and worked for 25 years in
‘common sexology’, where clients usually have no somatic cause for their sexual troubles.
Gradually Dr Gianotten’s medical roots directed him more to the area of ‘medical sexology’, where chronic disease,
cancer, physical impairment, and medical interventions are a major cause of people’s sexual troubles. He
worked up until the Dutch retirement-age as a medical sexologist in the University Medical Centers of Utrecht
and Rotterdam. Nowadays his attention is concentrated on three areas of interest: oncosexology, reproduction
sexology, and physical rehabilitation sexology. He still has a part-time job in a rehabilitation center.
In 2008 Dr Gianotten was editor in chief of the Dutch-language book ‘Sexuality in disease and physical impairment’.
He is the co-founder and a board member of the International Society for Sexuality and Cancer (ISSC) and
is responsible for education. He is associate secretary of the World Association for Sexual Health (WAS).
SExUAL ACTIVITY AND PEOPLE WITH HEMOPHILIA: THE PERSPECTIVES OF
A UROLOGIST AND A SExOLOGIST
For the majority of patients, hemophilia care professionals have developed a primary care function, covering
all health problems. That is one reason why sexuality has to be integrated into their approach, and also why
this topic is addressed here.
For young men in the Western world, hemophilia hardly has any sexual consequences. The exception being
iliopsoas; muscle bleeding as a result of (too) vigorous movements during intercourse or (too) vigorous muscular
tension during masturbation.
The elder generation, on the other hand, has to deal with several factors that interfere with optimal sexual
function.
In their early years bleeding damaged various joints. That has impaired the repertoire of sexual movements and
can be accompanied by pain and disturbing noises during lovemaking.
Being infected with the hepatitis C virus increases the prevalence of sexual dysfunction. The risk of getting a
sexual dysfunction doubles when treated with interferon. Various factors play a role here, among which are
depression and the sexual side effects of antidepressants. When interferon is combined with ribavirin antiviral
therapy it can cause a decrease in testosterone (negatively influencing sexual desire).
Being infected with HIV can cause additional sexual impairment. This is apparently partly a result of being
seropositive, and partly a result of the HAART approach.
Independent of the above mentioned reasons, elder age can be a reason for sexual disturbances. Although age
itself is not a reason for less sex, the accompanying chronic disease, the changing partner and the age-dependent
diminished ability to become aroused can all lead to a decreased sexual function.
The most important recommendation for health professionals is: communicate! Since patients are too shy to
bring up the subject of sexuality, the hemophilia health professional should proactively do so to explore existing
sexual dysfunctions.
There are good arguments to keep sexuality at an optimal level, not only because sexuality is an important quality
of life, but also because various aspects of sexual expression clearly are accompanied by health benefits.
In hemophilia the range of treatment modalities for sexual dysfunction is slightly narrowed; especially for
erectile dysfunction. Vacuum therapy and intracavernous injections are contraindicated and oral medication
with PDE5-inhibitors apparently can cause severe epistaxis.
When needed, the hemophilia care professionals should give information on various practical aspects of
sexuality. That can include suggesting suitable positions, recommending painkillers, reflect on prescribing
erection enhancing medication and also referral to a sexology expert.
64 65
NOTES
REFERENCES
• Gianotten WL, et al. Haemophilia. 2009;15:55–62
• Danoff A, et al. Am J Gastroenterol. 2006;101:1235–43.
• Kraus MR, et al. J Endocrinol. 2005;185:345–52.
• Ende AR, et al. AIDS Patient Care STDS 2006;20(2):75–8.
• Incrocci L and Gianotten WL. Disease and Sexuality. In:
Rowland DL, Incrocci L. (eds) Handbook of Sexual and
Gender Identity Disorders. Hoboken, John Wiley & Sons,
2008:284–324.
• Whipple B, et al. The Health Benefits of Sexual Expression. In: Tepper MS,
Owens AF (eds.) Sexual Health, Vol 1, Psychological Foundations, Westport:
Praeger. 2007:17–28
• Gianotten WL, et al. Sexual activity is a cornerstone of quality of life. An
update of ‘The health benefits of sexual expression”. In: Tepper MS, Owens
AF (eds.) Sexual Health, Vol 1, Psychological Foundations, Westport:
Praeger. 2007:28–42
• Hicklin LA, et al. J R Soc Med. 2002;95:402–3.
• Ismail H, Harries PG. Acta Otolaryngol 2005;125:334

66
Socrates' belief
Socrates believed in the immortality of the soul, and his conviction
that the Gods had singled him out as divine emissary seemed to
provoke both ridicule and annoyance from the Athenians.
LATE BREAKING NEWS
LIPLONG RESULTS
67

SESSION FIVE
* LATE BREAKING NEWS *
THE FIRST RANDOMIzED, ACTIVE CONTROLLED CLINICAL TRIAL TO INVESTIGATE
SAFETY AND EFFICACY OF A LONG-ACTING FVIII PRODUCT
JøRGEN INGERSLEV
Dr Jørgen Ingerslev is a Professor in Hemostasis and Thrombosis at the Aarhus University, and in the
Center for Hemophilia and Thrombosis in the Department of Clinical Biochemistry, Skejby University
Hospital, Aarhus, Denmark. He is also a Visiting Professor at King’s College Medical School in London, UK.
Dr Ingerslev graduated in June 1970 from the University of Aarhus, Denmark after receiving the Aarhus
University Gold Medal Award in Clinical Chemistry in 1968. He recently retired as the Director of the
Hemophilia and Thrombosis Center and as a Professor in Hemostasis and Thrombosis at the University
of Aarhus.
Dr Ingerslev is an appointed member and Senior Advisory Board member of the Scientific and Standardization
Subcommittee on von Willebrand factor at The International Society of Thrombosis and Haemostasis. He has
been an Editorial Board Member for many publications including Haemophilia and Thrombosis Research.
His list of published papers amounts to 235 articles. Amongst these, 207 appeared in journals with a peer
review system, 25 are review articles and book chapters.
68 69
NOTES