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and can be freely distributed

Clinical Practice Keywords Haemophilia/Clotting/

Bleeding/Factor replacement therapy
Review
Haematology This article has been
double-blind peer reviewed

In this article...
● C
 auses of haemophilia and how it affects patients
● Current treatments and future developments
● Nurse’s role in supporting people with haemophilia

Haemophilia: diagnosis, management

and nursing care of patients
Key points
Author Kate Khair is consultant nurse and clinical academic careers fellow, Great
Congenital Ormond Street Hospital.
haemophilia is a
lifelong, inherited Abstract Haemophilia is a rare bleeding disorder associated with a lack of coagulation
bleeding disorder factor VIII (type A) or IX (type B). Haemophilia A is the most common, affecting 1 in
NT SELF- associated with a 5,000 male births. The hallmark of severe haemophilia is recurrent and spontaneous
ASSESSMENT lack of clotting joint bleeds, which can cause permanent joint damage and bleeding in other
Test your factor locations, such as the skull; they can be life threatening. However, recombinant
knowledge. clotting factor and non-factor replacement therapies are transforming the outlook for
After reading this There are two main people with haemophilia, and more people are living with the disorder into old age.
article go to
types of This article describes haemophilia and its management.
nursingtimes.net/
NTSAHaemophilia
haemophilia, which
If you score 80% have identical Citation Khair K (2021) Haemophilia: diagnosis, management and nursing care of
or more, you will symptoms, but patients. Nursing Times [online]; 117: 10, 34-38.
receive a certificate treatment depends

A
that you can use
on which clotting
as revalidation
evidence. factor is missing dvances in the treatment and and 1980s – is still being felt, highlighted
care of haemophilia have by the revelations of an ongoing public
The hallmark of transformed this rare bleeding inquiry (infectedbloodinquiry.org.uk).
severe haemophilia disorder from a fatal disease Described as “the worst treatment disaster
is recurrent and into a long-term condition, with which in NHS history” (Reed, 2021), it led to more
spontaneous joint people are increasingly living into old age. than 3,000 deaths from hepatitis and HIV
bleeds which, if left However, the legacy of the contaminated in people with blood disorders. The UK
untreated, can cause blood scandal – in which around 5,000 began using recombinant (manufactured)
deformity people with haemophilia and other blood clotting therapies in the late 1990s, guar-
disorders in the UK were infected with anteeing such a tragedy will never happen
Some bleeds, such contaminated blood products in the 1970s again, but it took over 30 years to launch an
as those in the skull independent public inquiry into the
and soft tissue scandal (Bit.ly/THSMHSupport).
around airways or
other internal What is haemophilia?
organs, can be life Haemophilia is a rare bleeding disorder in
threatening which the body does not produce enough
of a protein that helps the blood to clot.
Recombinant There are two main types:
clotting factor and ● Haemophilia A – caused by deficiency
non-factor of the functional plasma clotting
replacement factor VIII;
therapies mean ● Haemophilia B (also known as
more people with Christmas disease, after the first
haemophilia are patient diagnosed) – caused by
living into old age Protests over “the worst treatment disaster deficiency of the functional plasma
ALAMY

in NHS history” clotting factor IX.

Nursing Times [online] October 2021 / Vol 117 Issue 10 34 www.nursingtimes.net

Clinical Practice
Review
Congenital haemophilia
Most haemophilia is congenital, caused by
an inherited X chromosome genetic muta-
tion that mainly occurs in males, although
female carriers may have mild, or rarely
severe, bleeding symptoms (Bit.ly/NORD-
HemophiliaA). People with haemophilia
usually have a family history of the dis-
order, but around a third of males diag-
nosed have no family history due to a
spontaneous mutation in the female line
that has not been inherited by a male
family member before (Srivastava et al,
2020; Khair, 2019).
Who is affected by congenital haemophilia?
There are an estimated 10,000 people with
haemophilia in the UK (Khair, 2019). Hae-
mophilia A is the most common type,
affecting around 1 in 5,000 male births,
with around 60% experiencing a severe
form; haemophilia B is less common,
affecting around 1 in 25,000 male births
(Khair, 2019; Bit.ly/NORDHemophiliaA).
Around 20% of people with mild
haemophilia are women; moderate-to-
severe forms in women are rare (Bit.ly/
HaemophiliaFemale).
Acquired haemophilia
Haemophilia can also be an acquired con-
dition that is not caused by a genetic
defect. This is a rarer and lesser-known
condition in which people with previously
normal haemostasis (clotting) develop
autoantibodies (inhibitors) against clot-
ting factors, most frequently factor VIII
(Kruse-Jarres et al, 2017). It occurs mostly
in frail, older people but can occasionally
be associated with pregnancy, particularly
occurring post partum, and with autoim-
mune disease in younger people. In around
half of all cases, it has no known cause; in
others, it is associated with malignancy,
autoimmune disorders and other condi-
tions (Kruse-Jarres et al, 2017; Bit.ly/NORD-
HemophiliaA).
People with acquired haemophilia
develop potentially life-threatening com-
plications associated with abnormal,
uncontrolled bleeding that is often sponta-
neous and severe (Kruse-Jarres et al, 2017).
This includes bleeding into the muscles,
skin and soft tissue, as well as during sur-
gery or after trauma. Symptoms of
acquired haemophilia include nosebleeds,
bruising, haematomas (solid swellings of
congealed blood), blood in the urine and
gastrointestinal or urogenital bleeding
(Bit.ly/NORDHemophiliaA).
SPL, ALAMY
Acquired haemophilia in frail, older
people can be challenging to manage and
Nursing Times [online] October 2021 / Vol 117 Issue 10
Legs of an 18-year-old with haemophilia and bleeding in the knee joint after surgery
Bleeding in the knee joint can occur
spontaneously in patients with haemophilia
is associated with a high mortality risk due
to underlying comorbidities, bleeding or
treatment. The main treatment is haemo-
static management and eradicating inhibi-
tors; recommendations for management
are provided in Kruse-Jarres et al’s (2017)
consensus paper. Although acquired hae-
mophilia is estimated to account for at
least a third of all haemophilia cases, it is
likely that it is underdiagnosed and misdi-
agnosed in real-world clinical practice
(Kruse-Jarres et al, 2017).
Clinical features
Haemophilia A and B have the same clin-
ical features, although treatment depends
on which clotting factor is missing and the
severity of symptoms (The Haemophilia
Society, 2017). There are three levels of
severity (phenotypes), defined by the
35
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and can be freely distributed
percentage of circulating factor in the
blood compared with normal levels:
● Severe (less than 1%) – this causes
frequent bleeding, often for no
apparent reason, most commonly in
the joints or muscles;
● Moderate (1% to 5%) – this is associated
with less-frequent bleeding, which is
usually not spontaneous but can be
prolonged after injury, surgery or a
dental procedure;
● Mild (6% to 40%) – this causes bleeding
that is usually only prolonged after
injury or surgery and may never be
spontaneous (Srivastava et al, 2020;
Makris et al, 2018; The Haemophilia
Society, 2017).
Haemorrhage is a main cause of mor-
bidity and death in people with haemo-
philia, although infectious diseases from
contaminated blood products have fea-
tured prominently in recent decades, par-
ticularly in people treated with clotting
factors before 1985 (Darby et al, 1995).
Without treatment, the prognosis is poor;
however, the development of recombinant
clotting-factor replacement therapies and
non-factor replacement therapy has
recently improved the outlook for patients
(Khair, 2019).
Diagnosis
When there is a family history of haemo-
philia, the disorder will be suspected and
diagnosed before, at, or soon after birth. If
there is no family history or the family is
unaware of it (for example, if recent gener-
ations have only included female carriers),
diagnosis will only be made when bleeding
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Clinical Practice
Review

Box 1. Common types of bleed in congenital haemophilia ● Prophylactically – replacement therapy

● Newborn – birth trauma, immunisation, circumcision, heel pricks
● Toddler – bruising, buttocks, scrotum, mouth, head trauma
● Pre-school and school age – joints and muscles (particularly ankles, knees, elbows)
● Adolescents and adults – joints and muscles (particularly ankles, knees, elbows),
sometimes more-serious muscle bleeds (such as in the iliopsoas related to sexual
activity), heavy menstrual bleeding in young women
Source: Bit.ly/RareBleeding
problems arise. Most cases of severe hae-
mophilia are diagnosed in the first year of
life, but mild or even moderate cases may
not be diagnosed for years, possibly into
adulthood, usually following prolonged
bleeding after injury or as a complication
of surgery or dental treatment.
Diagnostic investigations include:
● Patient history;
● Signs and symptoms of bleeding;
● Family history of bleeding;
● Blood tests, including coagulation
screening and factor levels, to confirm
diagnosis.
Signs and symptoms
Haemophilia should be suspected in
people presenting with a history of:
● Easy bruising in early childhood;
● Spontaneous bleeding for no apparent
or known reason, particularly into the
joints, muscles and soft tissues;
● Excessive bleeding after trauma or
surgery (Srivastava et al, 2020).
Common types of bleed in people with
congenital haemophilia are shown in
Box 1. The hallmark of severe haemophilia
is recurrent and spontaneous joint bleeds
that, left untreated, can result in crippling
deformity (Khair, 2019). These usually
appear when young children begin
walking and moving around; the first signs
can be discomfort and crying, along with
limping or reluctance to use the affected
limb (Khair, 2019; The Haemophilia
Society, 2017). The joint may be swollen,
warm and difficult to straighten, but with
no external discolouration or bruising
(Srivastava et al, 2020; Khair, 2019; The
Haemophilia Society, 2017).
Bleeds can also occur elsewhere in the
body, and complications depend on the
affected site: bleeds into the head, neck,
abdomen or gastrointestinal tract are life
threatening and must be treated as an
emergency (Butler, 2012). Intracranial
haemorrhage (ICH) is a particular concern
in babies and young children, as it can
cause seizures and paralysis, and remains a
significant cause of morbidity and mor-
tality after birth trauma (Khair, 2019). In
Box 2. Treating acute bleeds
World Federation of Haemophilia
guidelines (Srivastava et al, 2020)
recommend immediate treatment of
acute bleeds – ideally within two hours
– and say that in “severe bleeding
episodes that are potentially life
threatening, especially in the head, neck,
chest and gastrointestinal tract,
treatment with factor should be initiated
immediately, even before diagnostic
assessment is completed”.
Close coordination with the specialist
haematology team is needed, and
additional support can include rest, ice,
compression and elevation (Srivastava
et al, 2020). Pain management should
also be part of any treatment plan,
avoiding medicines containing aspirin or
non-steroidal anti-inflammatories.
adulthood, hypertension and increasing
age are also associated with ICH (Zanon
and Pasca, 2019). Other bleeding episodes
requiring prompt treatment include:
● Nerve compression from bleeding in
deep muscles, such as the iliopsoas
(inner hip muscle), often presenting as
numbness and pins and needles;
● Haematuria (blood in the urine);
● Deep lacerations;
● Epistaxis (acute nasal haemorrhage);
● Bleeding from the mouth or tongue
(Khair, 2019; Butler, 2012).
Affected women can present with all of
these symptoms as well as heavy men-
strual bleeding (Hirayama et al, 2019).
Treatment
The mainstay of treatment for haemo-
philia is preventing and managing
bleeding episodes by replacing the missing
clotting factor in the blood.
Standard factor replacement therapy
This involves an intravenous infusion of
recombinant factor VIII (for haemo-
philia A) or factor IX (for haemophilia B),
delivered in one of two regimens:
is given regularly to prevent bleeding
and long-term damage caused by
bleeding into joints and muscles, and
bleeding from minor injuries. This is
mainly used for children and some
adults with severe haemophilia and
some with moderate haemophilia who
have frequent bleeding problems;
● On demand – replacement therapy is
given to stop bleeding when it occurs.
This is generally used for people with
mild-to-moderate haemophilia, very
young children and some adults with
severe haemophilia who choose not to
take prophylaxis (The Haemophilia
Society, 2017).
International guidelines from the WFH
(2013) recommend prophylaxis for severe
haemophilia, although patients who dis-
like regular infusions may prefer treatment
on demand (Bit.ly/HaemophiliaTreat).
Prophylaxis is especially important in
children, because their articular cartilage
is more vulnerable to permanent damage;
it is usually started at around the age of
one, after the first or second joint bleed
(Khair, 2019). Infusions are usually three
times a week for haemophilia A, and twice
a week for haemophilia B; patients and
carers learn to administer them at home.
For very young children, or children whose
veins are difficult to access, this can often
necessitate a central venous access device
(Khair, 2019).
Minor bleeds can often be treated at
home, but acute bleeds need to be man-
aged in hospital; the treatment for acute
bleeds is outlined in Box 2. More than one
infusion may be needed, depending on the
site and severity of the bleed (The Haemo-
philia Society, 2017). People with mild-to-
moderate haemophilia can sometimes
bleed as much as those with severe haemo-
philia, who usually have their bleeding
controlled by prophylaxis. However,
patients having prophylaxis may still have
bleeds that require extra factor infusions,
particularly after injuries.
People with haemophilia who are about
to undergo a surgical or dental procedure
may need extra treatment, including factor
infusions or other haemostatic agents.
Extended half-life treatments
A newer type of factor replacement
therapy uses extended half-life factors, in
which the factor molecule has been modi-
fied by the addition of stabilising mole-
cules, which extend the half-life of the
infused factor. These can last longer in the
bloodstream than standard factor, so

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prophylactic infusions can be given less
frequently:
● Twice a week for haemophilia A;
● Weekly or fortnightly for
haemophilia B.
The reduced frequency of infusions and
increased levels of factor can decrease the
treatment burden (Khair et al, 2019). Bleeds
can also be controlled more quickly, often
requiring only a single infusion.
Emicizumab
Emicizumab is a non-factor replacement
therapy used for haemophilia A. It is injected
subcutaneously to prevent or reduce
bleeding episodes, but is not used to treat
bleeding (Bit.ly/HaemophiliaNonFactor).
The first commercially available product
in a new generation of bypassing agents, it
is a monoclonal antibody that works by
bridging activated factor IX and X to
restore the function of the missing acti-
vated factor VIII needed for effective blood
clotting (Bit.ly/NICEEmicizumab).
Emicizumab is available in the UK for
people with severe haemophilia A with
and without antibodies. It can revolu-
tionise care: treatment is a subcutaneous
injection, given once weekly for the first
four weeks, and then weekly, fortnightly or
every four weeks in the maintenance phase
(Khair, 2019). As more people with haemo-
philia survive into old age, emicizumab is
also useful for treating people who
struggle with repeated venous access or
who are no longer able to self-infuse, such
as those in residential care homes who
have congenital haemophilia.
In the UK, only a haemophilia compre-
hensive care centre can prescribe emici-
zumab and care is needed when co-infusing
it with other treatments because of poten-
tial thrombotic side-effects (Khair, 2019).
Desmopressin
Desmopressin stimulates the release of von
Willebrand factor from endothelial cells by
acting on the V2 receptor; it is used to:
● Control minor bleeding episodes in
people with milder forms of
haemophilia;
● Help prevent bleeding associated with
minor operations, including dentistry
(Haemophilia Society, 2017).
It is injected subcutaneously but can
also be delivered intravenously or as a nasal
spray. Side-effects include hyponatraemia
(low sodium levels) and seizures; fluid
retention can also occur, and patients are
asked to restrict fluids after treatment. Its
use is not recommended for children aged
under two years (Khair, 2019).
Nursing Times [online] October 2021 / Vol 117 Issue 10
Tranexamic acid
This drug helps hold a clot in place once it
has formed, and is helpful for mouth
bleeds, nosebleeds and heavy menstrua-
tion (The Haemophilia Society, 2017).
Given as a liquid, tablet or mouthwash, it
is often used with clotting factor or desm-
opressin.
“[In] the contaminated
blood scandal around 5,000
people with haemophilia
and other blood disorders
in the UK were infected
with contaminated blood
products”
Complications
Haemophilia can have many short- and
long-term complications; the main ones
are discussed below.
Inhibitors
The development of antibodies (inhibi-
tors) to clotting factor replacement thera-
pies is the main complication of contem-
porary care; it occurs in around 14% of
people with haemophilia A and 2% of those
with haemophilia B (Khair, 2019). Inhibi-
tors prevent clotting factor from working,
mainly affecting people with severe hae-
mophilia A.
When they arise, inhibitors commonly
develop during the first 50 treatment days,
and usually in the first 20 days. This means
that, in people with severe haemophilia A,
inhibitors generally appear in childhood,
while in those with mild-to-moderate
forms they tend to develop later in
life (Bit.ly/HaemophiliaBleeding). Periodic
screening for inhibitors should be part of
haemophilia care; patients also need
screening before any surgical procedure,
including dental work.
Treatment of inhibitors includes:
● Attempting to eradicate the underlying
antibody by building up immune
tolerance through regular exposure to
high doses of coagulation factor
(immune tolerance induction);
● Treating bleeding episodes with
infusions of bypassing agents factor
VIIa or activated prothrombin complex
concentrate (Khair, 2019);
● Prophylaxis with emicizumab.
Joint and muscle damage
Damage to muscles and joints caused by
serious or repeated bleeding is a main
cause of morbidity in severe haemophilia,
37
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and can result in chronic joint disease,
functional impairment and disability
(Khair, 2019). Bleeding into joints is a par-
ticular problem, as it can damage the syn-
ovium (joint lining), cartilage and sur-
rounding tendons and tissues, leading to
arthritic pain and reduced joint movement
and strength (Nacca et al, 2017).
Older people with haemophilia are likely
to have joint damage, due to limited access
to treatment when they were young, and
often require orthopaedic surgery. Prophy-
laxis and prompt treatment of bleeds means
children often now reach skeletal maturity
with well-preserved joint function,
although most people with severe haemo-
philia still experience joint problems at
some stage. Hanley et al’s (2017) best-prac-
tice guidance for managing acute joint
bleeds and chronic synovitis was published
by the United Kingdom Haemophilia
Centre Doctors’ Organisation.
Infection-related complications
Improved blood-donor screening in man-
ufacturing plasma-derived products and
the switch to recombinant clotting factors
has virtually eliminated the risk of transfu-
sion-transmitted infections in the UK.
However, there are still patients living
with the long-term health effects of trans-
fusion-transmitted viruses and their treat-
ments, and the psychological effect on the
families involved is only just being
acknowledged (Bit.ly/THSMHSupport).
Life-threatening complications
The most critical life-threatening compli-
cations of haemophilia are:
● Bleeding in the skull;
● Haemorrhages in the soft tissue around
airways or other internal organs.
Spontaneous ICH occurs in up to 8% of
people with haemophilia, and around 30%
of those will die from it (Hegde et al, 2016).
Patient care
All UK patients diagnosed with haemo-
philia should be registered with a haemo-
philia comprehensive care centre that pro-
vides core multidisciplinary care from
doctors, nurses, physiotherapists, psy-
chosocial carers and coagulation labora-
tory staff, who liaise with non-haemo-
philia specialists – including dentists and
surgeons – when necessary. People with
haemophilia carry a bleeding disorder
information card and have all aspects of
their care coordinated by their specialist
haemophilia team, even when care is
delivered in other settings (Srivastava et
al, 2020).
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Clinical Practice
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The nurse’s role
Clinical nurse specialists in haemophilia
practice at advanced levels have a pivotal
role in comprehensive care as part of the
multidisciplinary team, including pro-
moting evidence-based care, advocacy and
self-management skills for people with
haemophilia (Khair et al, 2014). The
changing role of the specialist nurse is dis-
cussed in detail by Khair (2021).
Nurses and other health professionals
should liaise with the specialist haemo-
philia team about all aspects of care for
patients with haemophilia, regardless of
the care setting or how patients present.
The increase in modified factor products
and alternative treatments means not all
patients are treated with standard clotting
factors (VIII and IX), and the patient’s spe-
cialist haemophilia team can advise.
In haemophilia, bleeding is often
internal, and nurses need to be able to rec-
ognise the signs. In addition, it is impor-
tant to be aware that older people with
mild-to-moderate haemophilia may not
bleed often enough to develop the skills to
self-treat at home, or may be reluctant to
learn; this means they might present more
often at hospital with bleeds than people
who have severe haemophilia.
Patients with haemophilia who are on
surgical wards will need infusions to pre-
vent potentially life-threatening bleeds.
Pain management is also more complex –
non-steroid anti-inflammatory drugs
cannot be used because they make
bleeding worse. Nurses caring for patients
with haemophilia must refer to the spe-
cialist haemophilia team.
Toddlers and young children pre-
senting with problems in weight-bearing
joints can be in severe pain; if a child is dis-
tressed, screaming and unwilling to use
the affected limb, nurses should not
attempt to pull it straight to demonstrate
mobility. Any child with haemophilia pre-
senting at the emergency department with
a head injury should be fast-tracked and
not go through the usual triage.
Children who have severe haemophilia
may need a central venous access device
for prophylactic infusions; this can pose
an infection risk and care may fall under
that of the community paediatric team. A
history of bruising and bleeds in children
who have not been diagnosed with haemo-
philia – particularly when there is no
family history – can raise safeguarding
issues; this is a main source of stress for
parents when their child is first diagnosed
(The Haemophilia Society, 2018). However,
it is also important to be aware that a
Nursing Times [online] October 2021 / Vol 117 Issue 10
diagnosis of haemophilia does not exclude
the possibility of non-accidental injury
and, if there is concern, usual child-pro-
tection procedures should be followed.
“All UK patients diagnosed
with haemophilia should
be registered with a
haemophilia comprehensive
care centre that provides
core multidisciplinary care”
Moving forward
Current treatment with prophylactic
factor replacement in severe haemophilia
reduces the frequency of bleeding and
improves patients’ quality of life. Use of
modified factor products and alternative
treatment options is reducing the burden
of treatment for some patients with hae-
mophilia, and has the potential to improve
patient adherence and outcomes, although
some challenges remain (Nogami and
Shima, 2019).
Like emicizumab, which disrupts coag-
ulation, there are other molecules in early
clinical trials that may impact on future
haemophilia care. Although these are, so
far, only in trials in adults, they show some
promise for other subcutaneous treatment.
Gene therapy may provide another
alternative. This works by delivering the
gene to make the missing factor, although
the person will still be a carrier of the
mutated gene (Bit.ly/HaemophiliaGene).
Clinical trials for gene therapy in severe
haemophilia have been extremely suc-
cessful, and one company has applied to
the European Medicines Agency and US
Food and Drug Administration for licen-
sure for routine clinical use. All this adds
up to a brighter outlook for people with
haemophilia; however, those who live for
longer with the disease will present with
new and different challenges and it will be
important to understand how to manage
haemophilia in frail, older people with sig-
nificant comorbidities. NT
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