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 1 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 2 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. 3 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. 4 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 5 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. 6 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 7 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), 8 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. 9 Who do I contact with queries and concerns? PNH Specialist Team contact details: Consultant Haematologist Dr Dupe Elebute Tel: 020 3299 1039 Email:[email protected] 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 10 www.kch.nhs.uk Catalogue number NW001 November 2010 Corporate Comms: 0191 Review date November 2013