Paroxysmal Nocturnal Haemoglobinuria (PNH) Information for patients

Paroxysmal Nocturnal Haemoglobinuria
(PNH)
Information for patients
King’s
King’s College Hospital is one of only two PNH Specialist Centres in England. The
other is St James’s University Hospital in Leeds. Together we provide a national
cinical service for all patients with PNH in England.
This leaflet explains Paroxysmal Nocturnal Haemoglobinuria
(PNH): what causes the condition, common symptoms and the
treatment available. We hope this information will help you
and your family understand PNH better. If you would like more
details or have questions about your care, please contact the
PNH Specialist Team at King’s College Hospital (see page 9).
What is PNH?
PNH is a rare blood disorder. It is
an acquired condition, meaning
it is not inherited so cannot be
passed on from parent to child.
PNH affects the bone marrow,
the factory that produces blood
cells, and leads to the production
of “weakened” blood cells that
are more easily destroyed by the
patient’s own special immune
system.
Destruction of the red blood cells
(haemolysis) causes the passage
of haemoglobin (a protein found
in red blood cells) in the urine,
producing the classic dark,
ruby-red or coca-cola coloured
urine which patients sometimes
experience. The condition is
named as a result of the original
description in which the patient
reported episodes (paroxysms)
of passing very dark urine
(haemoglobinuria) in the morning
following haemolysis that occurred
at night (nocturnal). However, not
all patients present in this manner
and there are other ways that
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PNH can affect individual patients,
described below.
PNH is associated with an
increased risk of developing clots
(thrombosis) and an increased risk
of developing bone marrow failure
conditions such as aplastic anaemia
(AA) or myelodysplastic syndrome
(MDS).
What causes PNH?
A lot of work is being done to
find out why PNH happens. We
know that if you have PNH your
bone marrow may not be working
normally. Some patients develop
PNH after they have had treatment
for a bone marrow disorder called
aplastic anaemia (AA), which
causes their bone marrow to
produce fewer blood cells.
You develop PNH blood cells when
your bone marrow produces a
gene called PIG-A. This genetic
‘change’ (mutation) happens after
birth which means you acquire
PNH rather than inheriting it.
Normal Blood Cells
PNH Blood Cells
Normal blood cells have
GPI anchors
PIG-A gene
codes for
GPI anchor
GPI anchor binds
different proteins to
the cell membrane
PIG-A gene
mutation
GPI anchor protein not
synthesised
Blood cells lack GPIanchored proteins
on cell surface
GPI anchor
Cell membrane
Cell membrane
The PIG-A gene causes your bone
marrow to produce blood cells
without a special protein known
as the GPI anchor, which protects
normal blood cells against your
own immune system.
destroy your PNH red blood cells
and results in the haemolysis that is
the main cause of all the disorder’s
symptoms and complications.
Without it, PNH blood cells are
not protected against a series
of complex reactions called
complement activation, which is
part of your body’s normal immune
response to help fight infections.
It is this lack of protection which
allows your immune system to
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Normal red blood cells are
protected from complement
attack by a protein shield
called a GPI anchor
Without this shield, PNH red
blood cells are destroyed
during complement
activation
Complement
Activation
Intact RBC
Haemolysis
Who gets PNH?
PNH is rare: only one–two
people per million worldwide are
diagnosed with it each year. There
are fewer than 1,000 people in the
UK with PNH. It affects all races
and men and women equally.
Although we diagnose most
patients when they are in their 30s
or 40s, children and older patients
can also develop the condition.
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What are the most common
symptoms?
You usually have a range of
symptoms that can include:
•Haemoglobinuria – you pass
dark red to black or cola coloured urine. Your urine may
be dark at any time of the day,
although this usually happens
first thing in the morning and
gets clearer as the day goes on
•Long-term tiredness or
lethargy. This is partly caused
by your low red blood cell count
or low haemoglobin (anaemia)
caused by the destruction of your
red blood cells (haemolysis)
•Yellowish discoloration of your eyes (jaundice)
•Stomach pains. You can have
these at any time but they are
usually worse when haemolysis is
happening. They may also
indicate that you are developing
blood clots in your abdomen
(tummy) or liver
•Dysphagia – you find it difficult
to swallow liquids and/or solids.
This can be worse during
episodes of haemolysis
•Erectile dysfunction – some
male patients may have difficulty
with maintaining an erection
of your penis. This can be worse
during periods of haemolysis.
What triggers haemolysis?
If you have PNH your red bloods
cells are always being destroyed
(chronic haemolysis). Sometimes
a large number can suddenly be
destroyed (acute haemolysis).
Haemolysis tends to increase if
you get infections, and in women
when you have a period or during
pregnancy. Some patients have
increased haemolysis after air
travel.
During haemolysis we advise
you to drink more fluids to help
your kidneys flush out the excess
haemoglobin and iron your body is
producing. If an episode continues
for more than 48 hours or you
also have severe abdominal pains
or pain in your loin/back you
should seek urgent medical advice
because you may be developing
clots or kidney failure.
Please note that every PNH
patient is different. You may
or may not have one or more
of the symptoms we have
described.
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Can PNH cause any other health
problems?
you may need dialysis to help
your kidneys get better
•Blood clots: You are more
likely to develop blood clots
(thromboses). These tend to
develop in unusual places such
as your gut (mesenteric vein
thrombosis), liver (Budd-Chiari
syndrome) or brain (cerebral vein
thrombosis). It is difficult to find
and treat these clots. They can
make you very ill and could cause
you to die
•Chronic kidney failure: You are
also at greater risk of longer term
(chronic) kidney failure because
of a build-up of iron in your
kidneys, and clots which can
develop in the blood vessels of
these organs.
•Bone marrow failure
disorders: You have a higher
risk of developing conditions
including aplastic anaemia (AA) and myelodysplastic syndrome.
These reduce your blood cell
counts so you are at increased
risk of infections or bleeding,
which can make you very ill and
could cause you to die
•Acute kidney failure: When
red blood cells are destroyed
during haemolysis, you produce
lots of extra haemoglobin which
passes out of your body through
your kidneys. If you have sudden
haemolysis, your kidneys may
not be able to cope with the
amount of haemoglobin that
they have to get rid of. This can
cause a serious condition called
sudden (acute) kidney failure and
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These complications can
significantly affect your quality
of life so it is important that
your PNH is identified quickly
and you are referred to a
specialist centre for advice.
How is PNH diagnosed?
Your specialist will examine
you and arrange for you to
have a urine test (to check for
haemoglobin in your urine) and
some blood tests to assess your
general health, including a full
blood count (FBC) to check if you
are anaemic, kidney function and
liver function tests.
To confirm you have PNH, your
doctor will send a sample of your
blood to a specialist laboratory
to check whether it contains any
PNH blood cells using a test called
flow cytometry. This shows the
percentage of red and white PNH
blood cells in your blood, but it
is more accurate on white blood
cells during or just after you have
had an episode of haemolysis or a
blood transfusion.
The group of blood cells affected
by the genetic defect that causes
PNH is also known as a PNH clone.
The extent to which your blood
cells are affected by PNH is often
described in terms of a clone size.
In general, if you have more
than 50% PNH blood cells this is
referred to as a large clone, 1050% PNH blood cells is a moderate
size clone and less than 10% is a
small clone.
How severely will PNH affect
my health?
PNH affects everyone differently.
Some people have only minor
symptoms which barely affect
their daily lives, while others
have regular episodes of severe
haemolysis which limit their
quality of life and cause serious
health problems. If you have a
large (greater than 50%) PNH
clone you are more likely to have
symptoms and are at greater risk
of complications such as blood
clots.
Does PNH affect fertility?
PNH does not usually affect your
fertility, but long-term illness and
previous treatment may reduce it.
Young men with PNH may find it
difficult to maintain an erection,
but there are now effective
treatments for this problem.
Does PNH affect pregnancy?
If you are pregnant you and your
unborn child are at increased risk
of complications. In particular, you
are more likely to develop blood
clots during pregnancy and for
up to six–eight weeks after birth.
Although we can reduce the risk of
these complications by monitoring
you carefully and using new
treatments, it is important that you
make the decision to get pregnant
only after you have discussed it
fully with a doctor with specialist
knowledge of PNH.
Which contraceptive methods
are safe?
Women should not use any of
the combined (oestrogen and
progesterone) oral contraceptive
pills because they increase your
risk of developing blood clots.
Progesterone-impregnated coils
such as the Mirena coil are safe,
as are barrier methods such as
condoms.
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How is PNH treated?
Because PNH affects everyone
differently, your treatment will be
tailored to your individual needs.
Your doctor will discuss all the
options with you and agree with
you the best treatment.
Most are what is known as
‘supportive therapies’. This means
they help to improve symptoms or
treat a specific complication but
they do not cure PNH. There is
only one treatment that can cure
PNH: stem cell or bone marrow
transplantation. Very rarely, PNH
clones gradually disappear on
their own over a number of years,
leaving you free of the condition.
The following treatments are
available in the UK:
1.Blood transfusion with
donated red blood cells. This
quickly raises your haemoglobin
levels and improves symptoms
such as anaemia and fatigue.
2.Folic acid tablets. This vitamin
helps your bone marrow
produce new red blood cells
quickly.
3.Iron tablets. We occasionally
prescribe these to you if you
need to replace the iron that
you are losing in your
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urine. But we use this treatment
very carefully as regular blood
transfusions can cause increased
iron loading in organs, such as
the liver and heart.
4.Anti-coagulation (blood thinning) medicines such as
heparin (injected under your
skin) and/or warfarin (taken
as a tablet by mouth) to treat
blood clots. You may need to
take warfarin to reduce the risk
of blood clots, but this
treatment has to be discussed
carefully because you are at
greater risk of bleeding if you
take anti-coagulation drugs long
term.
5.Eculizumab (Soliris)®. This is
the first drug treatment for PNH,
which became available in 2007.
Soliris® is an antibody which
blocks the complement reaction
and so reduces the destruction
of PNH blood cells. It cut the
need for blood transfusions in
up to 50% of patients treated in
clinical trials conducted
in Europe, North America
and Australia. In addition,
it significantly improved their
symptoms and quality of
life. You are given Soliris® by
an intravenous infusion drip
over 30 minutes once a week
for four weeks at first, and then
once every fortnight. It does
not cure PNH, so if you stop
having the infusions you are
likely to get symptoms again.
You can have this treatment
if you need more than four
transfusions a year or you have
recently had blood clots. Please
ask for a copy of our patient
information leaflet about this
treatment, ‘A Patient’s Guide to
Soliris® (eculizumab therapy)’
6.Stem cell (or bone marrow)
transplantation is the only
known cure for PNH. Your
bone marrow is replaced
by bone marrow donated by
someone who does not have
PNH. Possible donors include
a brother or sister or a
volunteer/unrelated donor who
is a suitable blood match. This
treatment has a number of
risks including bleeding,
infections and a reaction
between your stem cells and the
donor’s (graft-versus-host
disease) which may make
you very unwell during the
procedure or even cause you
to die. So we usually offer
you transplantation only if
you have severe complications
such as bone marrow failure
or life-threatening blood clots.
Please contact your specialist
if you would like to know
more about the benefits
and disadvantages of stem
cell transplantation, and we can
arrange for you to see one of
our transplant consultants.
Please ask for a copy of
our patient information leaflet
about stem cell/bone marrow
transplantation ’Blood & bone
marrow transplantation – The
Seven Steps’.
Further information and
support
Because PNH is such a rare
condition you may find it difficult
to find out more about it from
your GP or your haematologist,
and you are likely to be the only
patient with PNH at your local
hospital.
By being referred to one of the
England’s two specialist centres
– at King’s College Hospital in
London or St James’s University
Hospital in Leeds – you can get
information and support from a
dedicated team and meet other
people with PNH. For example, the
PNH Specialist Team at King’s can
arrange for you to be introduced
to another patient who has PNH
so you can find out more about
living with the condition. We
also encourage you to join the
PNH Support Group (see page 9),
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which is run by people with the
condition.
Recommended internet sites
http://en.wikipedia.org/
wiki/Paroxysmal_nocturnal_
hemoglobinuria
www.pnhdisease.org
www.pnhsource.eu
www.hmds.org.uk/pnh_info.html
www.pnhalliance.org.uk
PNH Support Group
The PNH Support Group meets
three–four times a year on
rotation between London, Leeds
and Birmingham. It gives you
the chance to talk about your
experiences and share information
with other people who have this
rare condition. It also advocates on
behalf of patients on matters such
as health insurance. The group
needs members with different
skills to help it become a registered
charity so it can start fundraising
activities such as sports days,
dinners and sponsored runs.
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Who do I contact with queries
and concerns?
PNH Specialist Team contact
details:
Consultant Haematologist
Dr Dupe Elebute
Tel: 020 3299 1039
Email:dupe.elebute@nhs.net
Dr Dupe Elebute leads King’s PNH
Specialist Centre and has been
involved in clinical trials into the
effectiveness of Soliris®, and other
PNH research.
Clinical Nurse Specialist Tel: 020 3299 3520
PNH Service Co-ordinator
Tel: 020 3299 1039
Email: generic email to be inserted
After 5.00pm and weekends/
bank holidays please contact
the main switchboard on
020 3299 9000 and ask for the
on-call haematology specialist
registrar.
Acknowledgements
We are also indebted to our PNH
patients who provided invaluable
and much needed input. We
welcome any comments or
suggestions you may have on
improving this leaflet to ensure
our patients and their relatives get
all the information they need to
help them cope better with the
diagnosis of PNH.
PALS
The Patient Advice and Liaison
Service (PALS) is a service that
offers support, information and
assistance to patients, relatives and
visitors. They can also provide help
and advice if you have a concern
or complaint that staff have not
been able to resolve for you.
The PALS office is located on the
ground floor of the Hambleden
Wing, near the main entrance
on Bessemer Road – staff will be
happy to direct you.
Telephone:
Textphone:
Fax:
Email: Counselling
The counselling service offers
free and confidential sessions to
all King’s inpatients, outpatients,
their relatives and friends. If you
would like to meet with one our
counsellors you can contact us
on 020 3299 1567, or 1567 from
within the hospital.
If you would like this leaflet in
a different format or language
please contact PALS on
020 3299 3601
020 3299 3601
020 3299 1878
020 3299 3626
kch-tr.PALS.nhs.uk
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www.kch.nhs.uk Catalogue number NW001 November 2010
Corporate Comms: 0191
Review date November 2013