Cochrane Database of Systematic Reviews

Psychological interventions for people with hemophilia

(Protocol)

Cassis F, Emiliani F, Pasi J, Palareti L, Iorio A

Cassis F, Emiliani F, Pasi J, Palareti L, Iorio A.

Psychological interventions for people with hemophilia.
Cochrane Database of Systematic Reviews 2012, Issue 11. Art. No.: CD010215.
DOI: 10.1002/14651858.CD010215.

www.cochranelibrary.com

Psychological interventions for people with hemophilia (Protocol)

Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

Psychological interventions for people with hemophilia (Protocol) i

Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
[Intervention Protocol]

Psychological interventions for people with hemophilia

Frederica Cassis1 , Francesca Emiliani2 , John Pasi3 , Laura Palareti2 , Alfonso Iorio4

1
Hemophilia Centre of Hospital Das Clinicas, FMUSP, San Pablo, Brazil. 2 Department of Psychology, University of Bologna, Bologna,
Italy. 3 Academic Haematology Unit, BICMS Pathology Group, London, UK. 4 Clinical Epidemiology and Biostatistic Department,
McMaster University, Hamilton, Canada

Contact address: Frederica Cassis, Hemophilia Centre of Hospital Das Clinicas, FMUSP, Umburanas street 307, San Pablo, Sao Paulo,
05464000, Brazil. frederica.cassis@gmail.com.

Editorial group: Cochrane Cystic Fibrosis and Genetic Disorders Group.

Publication status and date: New, published in Issue 11, 2012.

Citation: Cassis F, Emiliani F, Pasi J, Palareti L, Iorio A. Psychological interventions for people with hemophilia. Cochrane Database
of Systematic Reviews 2012, Issue 11. Art. No.: CD010215. DOI: 10.1002/14651858.CD010215.

Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT

This is the protocol for a review and there is no abstract. The objectives are as follows:

The primary purpose of this review is to evaluate if psychological therapies are helpful in improving the ability of people with hemophilia
to cope with their chronic condition.

The chronic aspect of hemophilia, its clinical variabilities and the differences in treatment availability across countries are all factors
that affect wellness in its emotional, intellectual, spiritual and behavioural dimensions.

The main objectives are to determine in people with hemophilia:

1. if any psychotherapies are effective in the management of the disease;

2. which phase of the patient’s life or phase of treatment, or both, this effectiveness occurs;

3. which psychological therapies (as described under Types of interventions) are more effective for any given situation.

BACKGROUND of hemophilia cases are due to a spontaneous mutation, meaning

that in such families there is no preceding history of hemophilia
(Hoots 2007; Rodgers 1999).
Internationally, the treatment of hemophilia varies widely, depen-
Description of the condition dent upon healthcare systems and infrastructure, governmental
A glossary of terms is available (Appendix 1). support and gross domestic product (GDP). In developing nations
access to hemophilia care and treatment is limited and disability
Hemophilia A and B (Christmas Disease) are rare chronic and in- consequent upon hemophilia is greater and more frequent, with
herited blood clotting disorders (Lozier 2004; Rodgers 1999). Al- significant reduced life expectancy and societal integration. There-
though hemophilia A and B are hereditary disorders, 30% to 40% fore, relationships, understanding, opportunities and attitudes to
Psychological interventions for people with hemophilia (Protocol) 1
Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
hemophilia per se and to patients with hemophilia, vary nation to only when a bleed occurs or pain is felt, or when day-to-day
nation and healthcare system to healthcare system. activities are interrupted or restricted by the consequences of
Clinically, hemophilia manifests through a wide and varied pattern bleeding, that the person with hemophilia becomes aware of the
of bleeding events. Most bleeding events in severe and moderate disease and feels himself or herself as a patient. This fact can lead
hemophilia occur in the joints and muscles. Bleeds may also occur to a denial of the bleeding disorder, which is a commonly used
in other soft tissues (often associated with trauma), or with surgi- mechanism, particularly in adolescence and to non-adherence
cal or dental interventions or generally in the oral cavity (tongue (Khair 2010; Penica 2008).
and lips lesions) (Lozier 2004). Epistaxis, hematuria and gastro- 3. Where treatment is unavailable, acute and chronic pain and
intestinal and iliopsoas bleeding may also occur (Kessler 2006). arthropathy become an experience from childhood onwards. The
The primary consequence of hemarthrosis is the develop- development towards a functional and productive adult
ment of chronic hemophilic arthropathy, which may occur if personality including undertaking studies and maintaining both
hemarthroses are recurrent, untreated, or inadequately treated. employment and relationships can become issues (Barlow 2007;
Chronic hemophilic arthropathy results in deformity, impair- Elander 2009; Plug 2008; Siboni 2009).
ment of joint movement, reduced mobility and chronic pain 4. Parents and relatives, due to the highly demanding situation
(Roosendaal 2006; Villaça 2004). and the complexity of the relationships in the setting of a
The standard medical treatment for hemophilia is factor replace- genetically transmitted disease, may have their own issues that
ment therapy, given by intravenous infusion either on demand contribute to making life easier or more difficult for the patient.
(when the bleeding occurs) or, in patients with severe hemophilia, 5. Feelings of anxiety, sadness and depression traducing in
prophylactically to prevent recurrent hemorrhage and so the de- mental health disorders are reported in hemophilia patients but
velopment of chronic hemophilic arthropathy (Iorio 2011). Some will vary in its influence in the individual’s quality of life
patients develop antibodies directed against missing or abnormal depending on cultural backgrounds, religious beliefs, family
clotting factor that inhibit the effect of transfused factor concen- support and others variables (Cassis 2007; Ghanizadeh 2009).
trates. In the presence of such antibodies (inhibitors), manage-
ment of both bleeding events and the hemophilia in general, is
significantly more complex. Therapies to control bleeding are ef- Description of the intervention
fective but very costly (Iorio 2010) and attempts to eradicate the
inhibitors are an option to be considered. Psychological interventions are used to help individuals with
Historically (until late 1980s), prior to the implementation of spe- hemophilia deal better with the different psychological issues that
cific donor testing and the development of effective virus inacti- they experience throughout their whole life cycle. These interven-
vation processes in the manufacture of plasma concentrates, many tions can include family members such as parents and siblings.
patients acquired blood borne virus infections (HIV or hepatitis The interventions are carried out in either treatment centers, in
C (HCV), or both) through the use of large pool plasma-derived facilities linked to the medical team and in a non-medical environ-
concentrates. This has been a significant legacy, physically and ment, such as an association of patients or any other community-
psychologically, of earlier generation plasma-derived factor con- based setting.
centrate treatments. There are different types of interventions based on the objectives
Besides medical treatment, management of hemophilia also repre- to be achieved and on other characteristics, such as the patient’s
sents a challenge due to the peculiarities of this inherited bleeding availability to frequently attend the center, or his or her physical
disorder. The ability to cope with the bleeding disorder and taking and emotional wellness state.
into account the self-perception of the patient are critical. Several These interventions include: cognitive therapy; psychodynamic
psychosocial issues should be considered in the management of psychotherapy; psycho-education; behavioural therapy; and sys-
hemophilia, including the following. temic therapy.
1. Hemophilia is a chronic and incurable condition, which
requires each individual to have an adaptation process to be able
to optimally interact with peers (Barlow 2007; Dunn 2008; Plug How the intervention might work
2008; Remor 2002; Stieltjes 2009; Talaulikar 2006). For
A better functional status (as measured with objective instruments)
example, sports are recommended by the World Federation of
and an improved quality of life are expected as a result of the in-
Hemophilia (WFH), but the choice and practice represent a
tervention. Physical limitations or impairment are not always cor-
psychosocial issue that requires perception of limitations,
related with a poor mental health quality (Stieltjes 2009) showing
expectations and cultural influences on the child and family,
how important adaptive coping strategies are in coping with living
along with the advice by the hemophilia centers (Mulder 2004;
with hemophilia’s issues. Reports on the importance of acceptance
von Mackensen 2007).
of hemophilia as part of oneself are well documented (Albrecht
2. Where treatment is available and prophylaxis is used, it is
1999; Beeton 2005).

Psychological interventions for people with hemophilia (Protocol) 2

Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Parents can receive support through counselling, from the moment METHODS
of diagnosis through the entire life cycle, with the aim of helping
to understand each cognitive stage of development of their child
(Bottos 2007). Children themselves can receive support through Criteria for considering studies for this review
play therapy. This preventive approach aims to avoid: rejection
of hemophilia; fear of reporting bleedings; and non-compliance
(Cassis 2007).
Types of studies
One of the outcomes usually measured to assess the effect of psy-
chosocial interventions is quality of life. Different approaches have All randomized controlled trials (RCTs), quasi-randomized trials
been undertaken with questionnaires to assess this outcome. For or controlled clinical trials (CCTs).
children there is the CHO-KLAT questionnaire (Young 2006)
and for children and adults, the Haemo-Qol instrument (Remor Types of participants
2002; von Mackensen 2004). There have also been studies of el-
derly patients (Siboni 2009). Patients with hemophilia of any age or gender, type A or B, any
severity (severe, moderate, mild), with or without inhibitors. Pa-
tients with HIV and or HCV are eligible for inclusion.

Why it is important to do this review

People with hemophilia, whether this is mild, moderate, or se- Types of interventions
vere, with or without inhibitors, often present with the effects This review targets all psychological interventions which have the
of psychosocial stressors. Psychological interventions to help cop- objective to promote emotional, intellectual and spiritual wellness.
ing with these psychosocial issues are often claimed to be help- Individual, group or family group therapy interventions are eligible
ful and needed by several hemophilia healthcare professionals and for inclusion. Family group therapy will be included if family
patients’s organizations in many countries. Various schemes and members are participating with the patient.
programs to provide support on emotional, cognitive and educa- The interventions are based on the issues we wish to explore: early
tional grounds have been proposed by psychologists, social work- understanding of the chronic condition (education); adherence or
ers and counsellors. Although many different interventions have compliance to treatment (on-demand or prophylaxis); inclusion
been used and published on, a systematic review in the field of in social life; and pain management (chronic or acute).
psychological therapies would provide a knowledge base illustrat-
ing which psychological therapies are often utilised and which are
proven effective. Psycho-education and low intensity psycho-educational
intervention (telephone, Internet, diaries as following up
tools)
Psycho-education means providing information and learning
about oneself and one’s own treatment aiming an increase in self-
OBJECTIVES
confidence for a better day-to-day life. It is also used to provide
The primary purpose of this review is to evaluate if psychologi- early coping strategies to the patient and his or her parents, to deal
cal therapies are helpful in improving the ability of people with with stressors linked to hemophilia and its peculiarities.
hemophilia to cope with their chronic condition. 1. Management of treatment for hemophilia A and B (including
those with inhibitors)
The chronic aspect of hemophilia, its clinical variabilities and the
2. Management of treatment for hemophilia and HIV or HCV,
differences in treatment availability across countries are all factors
or both
that affect wellness in its emotional, intellectual, spiritual and be-
3. Self-infusion therapy programs on-demand or on prophylaxis
havioural dimensions.
4. Port-a-cath procedure
The main objectives are to determine in people with hemophilia: 5. Learning and counselling with educational tools

1. if any psychotherapies are effective in the management of

the disease; Cognitive therapy
1. Investigate ways of thinking, perceiving and feeling, i.e. low
2. which phase of the patient’s life or phase of treatment, or
self-esteem, misunderstandings
both, this effectiveness occurs;
2. Inform and re-frame inappropriate thoughts or beliefs
3. which psychological therapies (as described under Types of 3. Monitoring thoughts, feelings
interventions) are more effective for any given situation. 4. Uses imagery, visualization with hypnosis or self-hypnosis

Psychological interventions for people with hemophilia (Protocol) 3

Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Behavioural therapy Search methods for identification of studies
1. Activity monitoring, re-organizing behaviours
2. Relaxation therapy, visualization and biofeedback
3. Communication skills training through flashcards, teach back Electronic searches
4. Goal setting We will identify relevant studies from the Cystic Fibrosis and Ge-
5. Decision making to solve problems netic Disorders Group’s Coagulopathies Trials Register.
The Coagulopathies Trials Register is compiled from electronic
searches of the Cochrane Central Register of Controlled Trials
Psychodynamic Psychotherapy (CENTRAL) (updated each new issue of The Cochrane Library)
1. Deal with the individual emotional, cognitive, physical devel- and quarterly searches of MEDLINE and the prospective hand-
opment since childhood searching of one journal - Haemophilia. Unpublished work is iden-
2. Investigate ways of thinking through the expression of dreams, tified by searching the abstract books of major conferences: the
fantasies, active imagination European Haematology Association conference; the American So-
3. Re-signify traumatic and or painful experiences by having new ciety of Hematology conference; the British Society for Haema-
insights into them tology Annual Scientific Meeting; and the Congress of the World
Federation of Hemophilia. For full details of all searching activ-
ities for the register, please see the relevant section of the Cystic
Systemic therapy Fibrosis and Genetic Disorders Group Module.
1. Learning new approaches to cope with problems between mem- We also plan to search: a clinical trials registry: ClinicalTrial.gov;
bers of the family EMBASE (www.embase.com); and PsycINFO/PsycLit(
2. The psychological frame can vary from psychodynamic, be- www.apa.org).
havioural or interactional therapy

Searching other resources

Types of outcome measures We will search conference proceedings of the International Society
for Thrombosis and Haemostasis from 1990 to the present day.
We will scan the reference lists of all retrieved publications and
Primary outcomes ’grey’ literature such as reports and doctoral dissertations that may
1. Mood - anxiety and depression (any measure with adequate contain psychological studies.
psychometric properties that identify psychiatric
symptomatology, emotional or behavioural difficulties in child or
adult) Data collection and analysis
2. Coping strategies for relief of pain, anxiety, early report of
bleeding, preparation for joint replacement and surgery,
complications such as HCV and HIV, and adherence to Selection of studies
treatment Two authors will independently assess study eligibility using a stan-
3. Quality of life (any measure that quantifies the extent to dardized form. We aim to solve any disagreements by discussion,
which the child or adult is able to participate in developmentally or if unsuccessful, by asking a third author. If we identify multi-
appropriate social activities in the field of education, ple publications on the same trial they will list all these references
employment, leisure time) together under one study identifier and use all available data.

Secondary outcomes Data extraction and management

1. Compliance or adherence to prophylaxis treatment Two authors will independently perform data extraction using a
2. Phyisical health standardized form. We aim to solve any disagreements by discus-
i) frequency of bleedings and emergency department sion, or if unsuccessful, by asking a third author. We plan to extract
visits the following: bibliographical data (authors, journal, publication
ii) hospital admissions year, publication type); study type; type of participants (patients,
iii) duration of hospitalisations carriers, carers); number of participants, intervention(s) number;
iv) presence of co-morbidities and type of comparator. If required, the authors will request any
3. Cost of psychological intervention additional data not found in the publication from the study au-
4. Family adjustment thors.

Psychological interventions for people with hemophilia (Protocol) 4

Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
We will group outcome data as follows: short-term (on treatment); The values of I2 lie between 0% and 100%. We will use a catego-
mid-term (end of treatment to three months); long-term (over rization of heterogeneity according to the following values:
three months). • not important (I2 values 0% to 40%);
• moderate (I2 values 30% to 60%);
• substantial (I2 values 50% to 90%); and
Assessment of risk of bias in included studies • considerable (I2 values 75% to 100%).
The standard risk of bias assessment tool incorporated in RevMan
will be used (RevMan 2011). Risk of bias will be assessed over the
Assessment of reporting biases
five domains of:
1. random sequence generation; We will assess the consistency of measurements and outcomes
2. allocation concealment; planned by the original Investigators during the trial and those
3. blinding; reported within the published paper by comparing the trial proto-
4. incomplete outcome data; cols (when available) with the information in the final publication.
5. selective outcome reporting. If protocols are not available, we plan to compare the ’Methods’
Assessment will be done in duplicate by the authors in the data and the ’Results’ sections of the published papers. We will also
extraction phase. Disagreement will be solved by discussion, or if use our knowledge of the clinical background to identify standard
unsuccessful, by asking a third author. We will assess the risk of outcome measures usually taken, but not reported by the trial in-
bias separately for any outcome for items 3 to 5, and report these vestigators.
(for any outcome and for the study) as low, high, or unclear. If we include a sufficient number of trials (10 or more), we will
attempt to assess whether the review is subject to publication bias
by using a funnel plot. If we detect asymmetry, we will explore
Measures of treatment effect causes other than publication bias.
For dichotomous outcomes we plan to calculate the risk ratio
(RR) and their 95% confidence intervals (CI). For continuous Data synthesis
data, whenever possible, we will calculate the standardized mean
We will extract data and input them into RevMan for any included
difference (SMD) and their 95% CIs.
studies (RevMan 2011). We will use a fixed-effect model for the
meta-analysis unless we find substantial or considerable hetero-
Unit of analysis issues geneity (as defined above), in which case, we will use a random-
effects model.
If cluster-randomised trials are identified we will check these for
If, given the data, we are unable to undertake meta-analyses, we
unit of analysis errors based on the advice given in chapter 16
will use a narrative approach supported by relevant tables.
of the Cochrane Handbook for Systematic Reviews of Interventions
(Higgins 2011).
Subgroup analysis and investigation of heterogeneity
We will investigate any heterogeneity we identify using subgroup
Dealing with missing data
analysis of potential confounding factors, if sufficient numbers (at
All the analyses will be by intention-to-treat. Since we do expect least 10 trials) are available. For this review, these confounding
an effect of treatment progressively increasing over time during factors will be:
treatment and progressively decreasing thereafter, we do not fore- 1. treatment;
see applicability of the last observation carried forward methods. 2. age;
We will then perform a sensitivity analysis with the best and worst 3. inhibitor status;
case scenario methods to assess effect of the missing data. 4. in different phases of life during treatment: moment of
diagnosis; childhood, self-infusion phase; port-a-cath; status and
treatment for HCV or HIV (or both); education level.
Assessment of heterogeneity
We will investigate heterogeneity between trials through visual
examination of the combined data presented in the forest plots Sensitivity analysis
and by using the I2 statistic together with chi-squared values and The authors will undertake sensitivity analyses to assess the ro-
their CIs (Deeks 2011) bustness of our review results by repeating the analysis with the
This measure describes the percentage of total variation across following adjustments:
trials that are due to heterogeneity rather than by chance (Higgins • exclusion of trials with unclear or inadequate allocation
2003) concealment;

Psychological interventions for people with hemophilia (Protocol) 5

Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 • exclusion of trials with unclear or inadequate blinding of
outcomes assessment;
• exclusion of trials with unclear or inadequate completeness
of follow-up.

REFERENCES

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APPENDICES

Appendix 1. Glossary

Term Definition

By-pass agents Clotting factor concentrates (factor VIII inhibitor bypass activity or FEIBA and
activated recombinant factor VII (rFVIIa) available for the treatment of bleeds in
patients with inhibitors

Carrier A female who has a gene for hemophilia. It is used to refer to a female who carries
the gene but has not the symptoms

Comprehensive care Medical care that covers several aspects of patient´ s well-being and health - mental,
emotional, physical. A comprehensive care team is multidisciplinary including hema-
tologists, nurses, social workers, psychologists, physiotherapists, dentists, orthopedic
surgeon and genetic counsellors

Psychological interventions for people with hemophilia (Protocol) 7

Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(Continued)

Concentrate A sterile freeze-dried, powdered product containing coagulation factors such as factor
VIII or factor IX for example. Such products may be produced from recombinant
technology or derived from large pools of human plasma. Plasma donations used for
such products are screened for contaminating viruses such as HIV, Hepatitis B and
C before use and then either heat treated, pasteurized or solvent -detergent treated to
further eliminate any residual virus and protect against viral transmission

Cryoprecipitate The material precipitated from fresh frozen plasma when it is thawed slowly at 2 to
4°C. Cryoprecipitates are rich in coagulation factors VIII, XIII, VWF, fibronectin
and fibrinogen. This solid remaining protein is re-dissolved by warming to give a
small volume of cryoprecipitate solution which can be used to treat hemophilia A

Epistaxis Bleeding from the nostril or nasopharynx.

Factor Blood components that help clot blood. Factor VIII and Factor IX are two of these
components

Factor VIII and Factor IX concentrates See ’Concentrate’ above.

Fresh frozen plasma (FFP) Plasma separated from whole blood by centrifugation, which is then frozen to below
-30°C within 8 hours of collection. This plasma contains all coagulation proteins
and clotting factors and is used widely as a replacement therapy for coagulation
problems. Historically it was the only source of factor VIII and IX and the only
treatment available for treatment of hemophilia. In the developed world it has been
superseded by factor concentrates as a source of factor VIII and IX. It remains an
important treatment for hemophilia in less well developed areas where concentrates
and cryoprecipitate may not be freely and easily available. Most FFP is not virus
inactivated

Hemarthrosis Bleeding or hemorrhage into joints.

Hematuria Presence of blood in the urine

Hematoma A localized swelling filled with blood (bruise) resulting from bleeding

Iliopsoas bleeding The large group of muscles in the hip area. Bleeding in these muscles is a significant
problem as large quantities of blood can accumulate in these muscle and nerve com-
pression may occur as a direct result

Immune tolerance induction treatment (ITI) A treatment to attempt to eradicate inhibitors in patients by continued exposure to
factor VIII or IX. Such regimens comprise may be either low dose or high dose con-
centrate regimes. It is a complex treatment with many issues to consider, e.g. costs,
variation in responses and complications dependent on subtype hemophilia (A or B)
, use of plasma derived or recombinant concentrates, use of adjuvant immunosup-
pressants

Inhibitor Antibodies to factor VIII or factor IX that inhibit the biological function of the
coagulation factor. Patients with hemophilia develop inhibitors as alloantibodies, that

Psychological interventions for people with hemophilia (Protocol) 8

Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(Continued)

is an antibody to a protein that is recognized as foreign. It is considered the most

serious complication in hemophilia

On demand therapy One of the models of treatment for people with hemophilia where clotting factor
concentrate are infused when bleeding occurs

Port-A-Cath Also called implantable venous access device (VAD) is a medical device that is im-
planted under the skin, usually on the chest wall. It is a titanium reservoir unit con-
nected to a catheter tube which is tunnelled under the skin and surgically inserted
into a vein. The reservoir unit, which has a robust silicone self sealing bubble to allow
insertion of a needle, is easily felt and provides a large target area that more easily
allows to injection and infusion of intravenous medications. It is frequently used
in children or other patients where access to veins to give intravenous injections is
problematic. In patients with hemophilia is often used to simplify regular prophylaxis
and immune tolerance treatments

Prophylaxis The regular infusion of factor concentrates to prevent bleeding in patients with
hemophilia. Infusions are given every twice or three times a week or on alternate
days dependent on type of hemophilia and patient requirements. Prophylaxis is either
primary or secondary
Primary prophylaxis is the use of prophylaxis to prevent bleeding or joint damage
that is commenced before any joint bleeding or damage has occurred. It is therefore
usually started before 2 years of age. Secondary prophylaxis is prophylaxis commenced
after joint bleeding or joint damage has occurred to prevent further deterioration or
progression

Recombinant factor VIII and IX Factor VIII and IXconcentrates produced using recombinant DNA technology. Being
free of human proteins such products are not at risk of transmission of blood borne
viruses and deemed very safe. Later generation products are also produced in an
environment free of adjuvant animal proteins

Symptomatic carrier A female that, when having the gene for hemophilia, has also reduced factor activity
level (generally less than 50%) that places the individual at risk of bleeding

CONTRIBUTIONS OF AUTHORS
Frederica Cassis and Alfonso Iorio drafted the original manuscript. All authors contributed to the further development and final draft
of the protocol.

Psychological interventions for people with hemophilia (Protocol) 9

Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
DECLARATIONS OF INTEREST
Frederica Cassis: I am a member of the IAB of HERO (hemophilia experiences results and opportunities) sponsored by Novo Nordisk
international. I have given paid presentations occasionally as a health consultant on psychosocial aspects in hemophilia. I am also a
member of the psychosocial committee of the World Federation of Hemophilia (WFH) and a volunteer for workshops on psycho-
education in hemophilia.

Psychological interventions for people with hemophilia (Protocol) 10

Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.