An Introduction toHaemophilia

We want people affected by bleedingdisorders to have the freedom to makechoices and seize opportunities

The Haemophilia Society

The Haemophilia Society was established in 1950 and is the onlynational patient organisation in the UK for people with haemophilia, vonWillebrand’s and related or associated bleeding disorders. Our vision is:

Freedom to make choices and seize opportunities for peopleaffected by bleeding disorders

Our services include:

A telephone and email helpline

Dedicated website with up to date information, downloads anddiscussion forums

Publications, short films, booklets and other resources for affectedpeople, their families and carers and for healthcare professionals

Events & holidays

Outreach and local support groups throughout the UK

Small grants through the Tanner Fund

Advocacy and campaigning

Specialist Information for:

Inhibitors

Women affected by bleeding disorders

Children, young people and families

Older people with bleeding disorders and those affected by mobilityor pain issues, or blood-borne viruses

All the quotes featured in this booklet come directly from people affectedby bleeding disorders. Pictures used with permission.

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An Introduction to haemophilia

Haemophilia is an inherited bleeding disorder, where an essentialclotting factor in the blood is either partly or completely missing. Itmainly affects males, although the gene that causes haemophilia iscarried along the female line.

This booklet is about living with haemophilia A and B. It aims to answercommonly asked questions and should be helpful for people directlyaffected by bleeding disorders and for those around them.

The outlook is now the best it has ever been for people with bleedingdisorders. Medical science has made huge advances. There are still nocures, but with modern treatment, children born now can look forward toa normal life expectancy taking advantage of education, training, sport,employment and travel opportunities.

A brief history

Haemophilia is perhaps the most well-known bleeding disorder and hasbeen known about for centuries. The condition was first noted whenbaby boys had bleeding problems after circumcision. It was realised thatthis appeared to run in families and then that it was passed along themother’s side.

In the 1800s haemophilia famously affected many members of the royalfamilies of England, Spain, Germany and Russia. Those affected weredirect descendants of Queen Victoria, the first known haemophilia carrierin her family. By the beginning of the 20th century scientists had workedout that haemophilia was due to a problem in the way that blood clots,but effective treatment using blood products only became available in theearly 1970s.

Even today the process of discovery still goes on, improving treatments,care and quality of life.

This booklet covers haemophilia only. For other disorders or moregeneral information, please see one of our other publications, look onour website, or get in touch with us by phone or email.

Tel: 0800 018 6068 www.haemophilia.org.uk

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What is haemophilia?Haemophilia is an inherited bleeding disorder in which the blood does notclot normally. People with haemophilia have much lower levels of one oftheir clotting factors, which are the blood proteins necessary for theclotting mechanism.

How does clotting happen?Blood is carried within the body through a network of blood vessels.Bleeding occurs when a blood vessel is injured and blood pours out. Thiscan happen as a cut to the skin, or within the body such as bruising orbleeding into tissues. When this happens, blood cells called plateletsstick together to form a plug to stem the flow of blood. There are severaldifferent clotting factors in blood which are proteins that act like glue toform a clot. The clot will stop the bleeding and begin the healing process.When someone has haemophilia they have low levels of one of theseclotting factors, so their blood doesn’t clot normally and they will bleedfor longer than usual. People with bleeding disorders don’t bleed anyfaster or any more than other people - it just takes longer to stop.

Simple diagrams ofbleeding (left)

and the clotting process(right)

Are there different types of haemophilia?Haemophilia A is due to a deficiency of clotting factor VIII (factor 8).Haemophilia A is also called classical haemophilia, and is the mostcommon type of haemophilia affecting one in 5,000 males.

Haemophilia B is also called Christmas Disease, named after the firstperson diagnosed with the condition. Haemophilia B is caused by adeficiency in clotting factor IX (factor 9) and affects one in 30,000 males.Because both types of haemophilia share the same symptoms andinheritance pattern, blood tests are used to identify whether someonehas haemophilia A or B.

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Are there different levels of haemophilia?Haemophilia A and B are classified as mild, moderate or severe,depending on the level of clotting factor in the blood. For example,someone with less than 1% of clotting factor in their blood is classifiedas having severe haemophilia. Moderate haemophilia is indicated byclotting factor levels of 1% to 5% of the normal range, and mildhaemophilia by factor levels of 5% to 30%.

People with moderate or severe haemophilia can have bleeds after aminor bump or knock, as well as spontaneous bleeds with no obviouscause. The term spontaneous is used when the cause of the bleed is notobvious, although in fact it’s often through minor injury or simple wearand tear.

Spontaneous bleeding in moderate and mild haemophilia is rare.Although everyone’s different, as a general rule someone with mildhaemophilia will usually have few problems and will generally only needtreatment after tooth extraction, surgery or an injury. Children with mildhaemophilia may also bleed more than adults.

‘My husband has haemophilia but he doesn’t like to talkabout it…I’d like to see some literature for people who

didn’t grow up with haemophilia in the family’

What is acquired haemophilia?Acquired haemophilia is a bleeding disorder which usually develops inlater life. It’s very rare, with about two new cases per million of thepopulation per year. Acquired haemophilia is an autoimmune condition,and occurs when the immune system develops antibodies against thebody’s own clotting factors, usually factor VIII. The antibodies inactivatethe factor VIII, resulting in a reduced factor level in the blood.

Acquired haemophilia usually develops in middle-aged or elderly peopleand can affect both men and women. Certain things may act astriggers for the immune system to develop antibodies to the body’s ownfactor VIII, including pregnancy or surgery, after developing certaintypes of cancer or conditions such as rheumatoid arthritis, or eventaking certain medications. However, it can also happen for no obviousreason. It’s recommended that anyone with acquired haemophilia istreated at a comprehensive care centre, where the condition can oftenbe resolved.

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How do you get haemophilia?Haemophilia is a genetic condition that is usually inherited. This meansthat there is usually a history of haemophilia in the family, but one inthree children with haemophilia is born into a family with no history of thecondition.

Haemophilia is an X-linked recessive condition. While men have thecondition, the gene that causes it is carried by women and is passedthrough the female line in the family. The chances of having a child withhaemophilia remains the same for each pregnancy for women who carrythe haemophilia gene.

(left) diagram of an X-linkedcondition such as haemophilia

Rarely, a woman can inherit‘true’ haemophilia and haveserious bleeding problems. Thishappens when her unaffectedX-chromosome is inactivated,and is very rare. However,about one-third of femalecarriers of haemophilia havelow clotting factor levelsthemselves and have ableeding tendency similar tomild haemophilia.

How is it inherited?The cells which make up our bodies are programmed with instructionsfrom our parents. These are the genes that hold the genetic instructionsfor life. Genes are carried on structures called chromosomes. Everyonehas 46 chromosomes in their body. Two of the chromosomes determinethe sex of a baby. They are the X and Y chromosomes. Females havetwo X chromosomes (XX); males have an X and a Y (XY). A child willinherit a chromosome from each parent. Males get an X chromosomefrom their mother and a Y from their father. Females get an Xchromosome from each parent. The genes for clotting factors VIII and IXare on the X chromosome. There is no gene for clotting on the Ychromosome. Only one of the female’s X chromosomes is affected by thegene that causes haemophilia.

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If the mother carries the haemophilia gene and the father does not havehaemophilia:

· A male child will have a 50:50 chance of having haemophilia, ashe will inherit one of his mother’s X chromosomes. If it is theaffected one he will inherit haemophilia.

· A female child will have a 50:50 chance that she will carry thehaemophilia gene, as she will inherit one of her mother’s Xchromosomes

For children of men with haemophilia (when the mother isn’t a carrier):· A female child will be a carrier, as she will have an unaffected X

chromosome from her mother and the affected X chromosomefrom her father. All daughters of men with haemophilia inherit theaffected X chromosome and are therefore carriers. They areknown as obligate carriers

· A male child will not be affected, as he will inherit his father’sunaffected Y chromosome and his mother’s unaffected Xchromosome. The son cannot pass haemophilia on to hischildren.

‘We were prepared for the chance ofour baby having haemophilia but asit was a 50/50 chance we were beingoptimistic… However the literaturewhich the Society has provided has

been so helpful’

The severity of haemophilia stays the same in a family. In other words, ifthere is a family history of mild haemophilia, a carrier of haemophiliafrom that family will only pass on a mild form of haemophilia.

If you would like more information on accessing genetic counselling,please see our booklet A General Introduction to bleeding disorders.

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What are the symptoms of haemophilia?The major symptom of severe haemophilia is internal bleeding intojoints, muscles and soft tissues. All of us do a small amount ofdamage to our joints and muscles as we go about our everyday lives,and repair that damage automatically and unnoticed. For someone withhaemophilia, however, the tiny breaks in the blood vessels in joints andmuscles may continue to bleed.

Many children with bleeding disorders also have nose and mouthbleeds and some adults will continue to have these types of bleeds.Children with haemophilia often bruise more easily, especially whenthey’re learning to walk. This is often when they are diagnosed. Formore information on this and what to do if a child is showing a lot ofbruises, see our General Introduction booklet.

With mild or moderate haemophilia minor injuries may heal normallybecause there is some clotting factor activity in the blood, so this maynot be diagnosed until the person is older. In most cases, minor cutsand scratches don’t pose any problems for people with bleedingdisorders.

‘I never let haemophilia stand in my way’

Signs of a bleed

(left) diagram of a joint bleedPeople will often feel an ache, tingling orirritation in the affected area, so they cantell when they’re having a bleed. Withouttreatment there will be pain, stiffness andlimited use, and the site of the bleed willget hot, swollen and more and moretender. For children, they may avoidusing their arm or leg or they might cryfor no other obvious reason.

The most common joints affected bybleeding are the ankles, knees andelbows – particularly in childhood. Theseare often called target joints. It’simportant to give clotting factor

treatment and rest the joint immediately, as this will help thehealing process.

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As well as ankles, knees and elbows, bleeds also occur into the largeball and socket joints, such as the shoulders or hips. The number ofbleeds can be unpredictable: one person may find they have internalbleeds three or more times a week, and another three or four times ayear. Children tend to bleed more often than adults, unless they are onregular prophylactic treatment.

Joints and muscles that have been affected by repeated bleeds canbecome a target for further bleeds. It’s really vital to get the propertreatment and rest to avoid stiffness and pain in future.

‘My son has severe haemophilia. He is 13 months oldand bruises a lot as he is learning to walk and crawl ’

How do you get treated?Haemophilia A and B are treated by replacing the missing clotting factor:factor VIII for haemophilia A and factor IX for haemophilia B. Becausethe clotting factors are large molecules they can’t be taken by mouth orby injecting them just under the skin. Instead they have to be given into avein, by intravenous injection. Treatment can be:

on demand - clotting factor concentrate given before surgicalprocedures, after an injury or once a bleed has started. Or

prophylactic - clotting factor concentrate given regularly to try toprevent bleeds happening. In haemophilia A it is routinely given threetimes a week (more or less depending on the person). In haemophilia Bit is usually given twice a week (or more frequently if necessary). Veryyoung children often need more regular injections as they use up thefactor more quickly.

Factor can be:Recombinant: a genetically engineered concentrate. Most children withhaemophilia in the UK now receive recombinant factor, unless they havean inhibitor. Or Plasma-derived i.e. made from human blood plasma(the part of the blood containing platelets and clotting factors)

In the UK all patients with haemophilia A and B are entitled to receiverecombinant factor VIII or IX. These are artificial products that are freefrom human plasma, and therefore carry no risk of passing on blood-borne viruses. If you are still treated with plasma, it is made as safe aspossible with careful screening and heat-treating techniques to kill anyviruses.

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Treatment for moderate and severe haemophiliaModern treatment for people with moderate or severe haemophilia aimsto prevent bleeding, pain and joint damage. This involves prophylactictreatment: regular injections of factor concentrate two or three times aweek to keep clotting factor levels high enough to prevent spontaneousbleeds. These days prophylaxis is the usual way to treat children withsevere haemophilia. Thanks to prophylaxis, most young people withhaemophilia have a good quality of life.

‘My son has mild haemophilia and has been lucky. He’sonly been given factor VIII on very few

occasions, generally for planned operations or after(usually stupid!) accidents’

Is there treatment for mild haemophilia?Some people with mild haemophilia A, as well as female carriers with ableeding tendency, are treated with a drug called desmopressin(DDAVP), which is a synthetic hormone, not a blood product.Desmopressin works by releasing FVIII from its storage sites in bloodvessels, but there needs to be some factor VIII present for this to work,and it doesn’t work for people with haemophilia B.

Tranexamic acid helps to stabilise the clot. It slows down the body’snatural process of breaking down a clot: this helps to stop bleeding andpromotes the healing process. It is often given in tablet form, but can begiven in syrup form or intravenously. It is used to treat minor bleedingepisodes, such as nose bleeds, and it can be used in combination withother medications such as DDAVP or clotting factor concentrates. Thesyrup form is recommended for children as they find it easier to take.

People with mild or moderate haemophilia can sometimes have seriousproblems because they may not recognise the signs and symptoms of ableed as they have them so rarely, or may not contact the haemophiliacentre before having surgery or dental work.

Someone with mild haemophilia should always tell any medicalprofessionals they see about their condition. For any injuries or ongoingmedical treatment, always contact the haemophilia centre for advice andthink about carrying a medic alert card or bracelet.

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Can you treat yourself at home?Factor concentrates can be stored at home which allows most peoplewith severe haemophilia to treat themselves, either as on-demandtreatment or as prophylaxis. You can either pick up the factor andequipment from the centre or in most areas, arrange delivery at home.Treatment centre staff will have information about this service.

Specialist staff in treatment centres will teach parents how to care fortheir children and, most importantly, how to give them an intravenousinjection. Most children will eventually learn to give themselvesinjections, and this can start at an early age. Adults can also be taught totreat themselves. The only reason you might not learn to self-treat is ifyour veins are hard to access or there’s another complication such as aninhibitor.

Giving a child an injection into a vein can be difficult for the parent aswell as the child and the haemophilia specialist. Where medicallyadvised, a device such as a Port-a-Cath® (an indwelling catheter) canbe fitted. This uses a tube and chamber placed under the skin of thechest and is an easier way for some parents to give their child aninjection. Port-a-Caths are particularly helpful when the child has veinsthat have not yet developed. They are also sometimes used for adultswho have difficulty finding and injecting into a vein.

(left & right)intravenous

infusions

Home treatment has allowed greater freedom and quality of life forpeople affected by haemophilia. They can go to school or work regularlyand have greater control over their home, student, working and sociallife, simply by being able to carry treatment around. However it’s stillreally important to have telephone contact with the treatment centre atany time of the day or night to discuss any problem that might arise.

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What are the possible complications of haemophilia?

PainThere are two causes of pain in bleeding disorders; acute pain isexperienced during a bleed, and chronic arthritic pain which hasoccurred through repeated bleeding into joints over a period of time.Prophylactic treatment is aimed at stopping this kind of long-term painand many young people with haemophilia have never experienced it.

Taking painkillers can be helpful and allow people to get on with theirlives. People with haemophilia vary in how often they take painkillers,but research has shown that they often give quite a lot of thought towhether they are using too much.

People with bleeding disorders should never take aspirin in any formbecause it makes bleeding worse. Other drugs, like non-steroidal anti-inflammatory medicines (such as ibuprofen), may need to be avoided -your centre will advise on this. Anyone who is considering using anyother medication or herbal remedies should ask their specialist foradvice beforehand.

As well as the usual medication, another effective way to treat the painof bleeds is with the PRICE regime of protection, rest, ice, compressionand elevation. It is important to stop physical activity and restimmediately symptoms appear, ideally as soon as you feel the bleedstart, rather than waiting until pain actually prevents activity. You shouldcarry on resting until the pain eases, and the bleed has stopped. Manypeople also use ice packs and elevate the affected area.

For more information on coping with pain please get in touch and wecan send you some suggestions.

Mobility problemsIn the past, most people with severe haemophilia had reducedmobility, linked to pain and stiffness caused by repeated bleeding. Withnew treatments this should be hugely reduced, but people can stilldevelop problems such as poor posture or way of walking tocompensate for areas that are sore or weak. Seeing a physiotherapistcan really help with these kinds of issues and stop them becomingserious. If you don’t have access to a physiotherapist get in touch withthe Society to hear about some options.

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InhibitorsInhibitors are probably the most serious complication in modernhaemophilia treatment. An inhibitor is when the body develops anantibody to factor concentrates, mistakenly recognising it as somethingharmful for you. This happens in around 15-25% of people withhaemophilia A and it seems to be on the increase. Inhibitors can occurmore rarely in haemophilia B and other disorders.

Having an inhibitor means your normal treatment won’t work as well, sowhen a bleed does happen it will be more difficult to treat. You might beadvised to limit the kind of physical activity you do or even use awheelchair to rest in from time to time.

Inhibitors can be mild or severe, and mild inhibitors (also called low-titre) generally cause little difficulty with treatment. People with mildinhibitors will need more clotting factor treatment more often than usualin order to overpower the effect of the inhibitor.

‘An inhibitor is when your body does not like the factormedicine any more so it fights it and then the factor

doesn't work’

A few people develop high levels of the inhibitor (also called high-titre),and for this they may need to use another treatment which bypasses theneed for factor VIII or factor IX. There are two basic strategies used totreat patients with inhibitors.

To help control bleeding episodes there are two equally effectiveproducts. NovoSeven® (recombinant factor VIIa) a geneticallyengineered clotting factor, and FEIBA® (factor eight inhibitor bypassingagent), which is a plasma-derived product containing several otherclotting agents that help to stop bleeding.

To eliminate the underlying inhibitor immune tolerance therapy (ITT) isused which aims to train the body’s immune system not to reject theclotting factor treatment. It involves daily injections of either factor VIII orfactor IX for long periods of time, usually 9 – 24 months. About 80% ofpatients can get rid of their inhibitor by going through this treatment;however the Haemophilia Society recognises that dealing with inhibitorscan put a lot of strain on people and their families. For this reason weoffer an Inhibitor Support Group with specialist information, events, andsupport.

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What’s next for haemophilia?

‘My advice to anyone who knows someone withhaemophilia would be to not treat them differently’

There have been major advances in haemophilia care in recent years,and this is still going on. For people with haemophilia, geneticallyengineered recombinant factor VIII and IX are now the first line oftreatment, and carry no known risks of viruses. Prophylaxis (regulartreatment to prevent bleeds) is used increasingly, and has had a verypositive impact in preventing joint damage. Because of this, theprospects for young people with haemophilia are excellent.

The next realistic and big advance will be longer-acting factor with thepossibility of fewer injections for prophylaxis and treatment of bleeds.Work is in progress on recombinant factor VIII in particular, and factor IXwith an altered structure, which is less likely to lead to inhibitors.

Finally, advances in genetic science mean that the use of gene therapyto treat bleeding disorders is a real possibility and good progress hasbeen made in studies in this area. The research into haemophilia A & Bis still at an early stage, but gene therapy is a very encouraging prospectfor the future.

‘We have the chance of getting the most productivediscourse between patients, families, carers, medical

professionals and researchers so we find the answers,more effectively, by working together’

Resources

The Haemophilia Society produces a range of resources including DVDs,publications, and online information. For an up-to-date list as well asdownloads, films and more, please go to our website atwww.haemophilia.org.uk

Our other websites:www.womenbleedtoo.org.ukwww.inhibitorsupportgroup.orgwww.youngbloods.org.uk

There are also several useful external websites:www.wfh.org – the website of the World Federation of Hemophiliaoffers a searchable database of treatment centres worldwide.www.hemophilia.ca -the Canadian Hemophilia Society’s website has arange of useful downloads.www.ukhcdo.org – the website of the UK Haemophilia Centre Doctors’Organisation, where you can find patient information, servicespecifications, and lists of UK haemophilia centres.www.travelfactor.co.uk – website run by Baxter healthcare whichoffers factsheets in different languages.www.factorfitness.co.uk - website run by Bayer focussing on sportand physiotherapy.www.medicalert.org.uk - a registered charity offering a range of medicalert jewellery.www.bpl.co.uk - the UK Blood Products Laboratory produce a range ofuseful booklets, including some on rarer disorders.

Other pharmaceutical companies also produce useful patient bookletsand information—look on their websites for support.Haemophilia Society Publications:A General Introduction to bleeding disorders (2008)An Introduction to rare bleeding & platelet disorders (2008)A Guide for Women Living with von Willebrand’s (2007)

Regular magazines and newsletters including HQ, Female Factors,Young Bloods, and the Inhibitors magazine.

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The Haemophilia Society would like to thank BaxterHealthcare for providing the funding for thisindependent information booklet.

We would also like to thank the people affected bybleeding disorders and the healthcare professionalswho contributed and commented on the text, including:Debra Pollard, Dr Paul Giangrande, Richard Oakley,Robert James, Eileen Ross, Dr Mike Richards, GeorginaRobinson, Ian D’Young, Colette Romdhani

Our thanks also go to the World Federation ofHemophilia who kindly gave permission for thereproduction of their images.

The Haemophilia Society 2012 (reprint)

0800 018 6068www.haemophilia.org.ukinfo@haemophilia.org.uk