Understanding haemophilia · Understanding haemophilia CHAPTER 2 2.1 CHAPTER 2 Haemophilia is an inherited bleeding disorder where blood doesn’t clot properly. It is caused when

Understanding haemophilia

CHAPTER 2 2.1

CHAPTER

2

Haemophilia is an inherited bleeding disorder where blood doesn’t clot properly. It is caused when blood does not produce enough of one of the essential clotting ingredients.

These ‘ingredients’ are clotting factors — proteins in the blood that control bleeding. The missing ingredient that causes haemophilia is usually either factor VIII (8) or IX (9). Roman numerals are used when referring to clotting factors.

• Haemophiliaisaninheritedconditioncausedbyagenealteration.

• Therearetwotypesofhaemophilia–AandB.

• Haemophiliacanbemild,moderateorsevere.

• Haemophiliaismostcommonlydiagnosedinboys.

• Ifyouareconsideringhavingmorechildren,thereissupportavailable to help with your decision.

KEY POINTS

Blood clotting and bleedingUnderstanding how bleeding starts and stops

Bleedingstartswhenacapillary(smallbloodvessel)isinjuredandbloodleaksout.

Whenthishappens,thecapillarytightensuptoslowthebleedingandblood cells called plateletsmakeaplugtopatchthehole.

Forpeoplewithouthaemophilia,themanyclotting factors in plasma (part of theblood)knittogethertomakeaclotovertheplug.Thismakestheplugstronger and stops the bleeding.

ClottingfactorVIIIandfactorIXareessentialtomakingthebloodclot.

UNDERSTANDING HAEMOPHILIA

2.2 CHAPTER 2

Source: Hemophilia in Pictures. © WFH 2005. http://www1.wfh.org/publications/files/pdf-1311.pdf

Normal clotting process

Clotting factor activity

Normal clotting process

Forpeoplewithhaemophilia,oneclottingfactorismissing, orthelevelofthatfactorislow.

Thismakesitdifficultforthebloodclottoformandstayformed,sobleedingcontinuesforalongerperiodoftime.Bleedingdoesnothappen any faster than for someone without haemophilia.

Peoplewithhaemophiliamayexperience‘rebleeding’atthesiteofaninjury after the initial bleeding has stopped. This is typical of the bleeding associated with haemophilia.

Oneaspectofhaemophiliatreatmentinvolvesinjectingthemissingfactor so blood can clot normally. This is called ‘factor replacement therapy’.

A person with haemophilia does not bleed any faster than a person without haemophilia,butthebleedingcontinuesforlongerifitisnottreated.

There is a myth that people with haemophilia bleed to death from a cut. This is NOT true.

Internal bleeding (often referred to as a ‘bleed’) is the biggest problem for peoplewithhaemophilia.Prompttreatmentwill,however,reducemost problems associated with bleeding.

see Chapter 3 for more information on bleeds and Chapter 4 for more information on treatment.


CHAPTER 2 2.3

Clotting in haemophilia

Source: Hemophilia in Pictures. © WFH 2005. http://www1.wfh.org/publications/files/pdf-1311.pdf

Clotting factor activity

Clotting in haemophilia

Types of haemophiliaTherearetwotypesofhaemophilia,howeverbothhavethesamesymptoms.

• HaemophiliaA (also called classical haemophilia) is the most common formandiscausedbylowlevelsofclottingfactorVIII(8).

• HaemophiliaB (sometimes called Christmas disease) is caused by lowlevelsofclottingfactorIX(9).

HaemophiliaAisfivetimesmorecommonthanhaemophiliaB.

Severity of haemophiliaYourchildmayhavemild, moderateorseverehaemophilia.Theseverityofhaemophilia depends on the amount of clotting factor in their blood.

The physical effects that your child may experience will depend on whether theyhavemild,moderateorseverehaemophilia.Effects varyfromchildtochildandcanevenvarybetweensiblingswithhaemophilia ofthesameseverity.Withregulartreatment,bleedingepisodescanbekept to a minimum.

The‘Severityofhaemophilia’tableprovidesaguidetothesymptomsofmild,moderateandseverehaemophilia.


2.4 CHAPTER 2

By understanding the severity of your child’s haemophilia and their pattern of bleeding over time, you will know what is likely to cause bleeds, how they will affect your child and how best to help them.

PARENTTIP


CHAPTER 2 2.5

Severity of haemophilia

ThenormalleveloffactorVIIIorIXinaperson’sbloodisbetween50%and150%

Severity and factor level

Mild haemophilia5%–40%ofnormal clottingfactorlevel

Moderate haemophilia1%–5%ofnormal clottingfactorlevel

Severe haemophiliaLessthan1%ofnormalclottingfactorlevel

What to expect

• Usually only bleeding problems following a badinjury,havingteethtakenout,surgeryormedicalproceduresthatpiercetheskin.

• Mightneverhaveableedingproblemrequiring medical attention.

• Might not be diagnosed until later in life if notplayingcontactsportsandhavenot hadanyinjuriesoroperations.

• Femalesmighthavebleedingproblemswith periods (menstruation) or childbirth.

• Mighthavebleedingproblemswithminorinjuries,suchassportinginjuries.

• Likelytohavebleedingproblemsafterhavingteethtakenout,surgery,medicalproceduresand/orabadinjury.

• Occasionallyhaveableedingepisodefornoobviousreason(‘spontaneousbleeds’).

• Oftenhavebleedsintojoints,muscles and soft tissues.

• Canhavebleedingepisodesfornoobviousreason (‘spontaneous bleeds’) as well asaftersurgery,dentalworkorinjuriesincludingminorbumpsandknocks.

Please note: this table is a guide only.


2.6 CHAPTER 2

Can factor levels change over time?Ifachildisbornwithseverehaemophilia,theyarelikelytohaveseverehaemophiliaovertheirlifetime.Thefactorlevelsofpeoplewithmildhaemophiliacanfluctuateovertimebecausetheirfactorlevelscanbeaffectedbythingssuchasstress,infectionorsurgery,butgenerallytheirlevelswillremainintherange formildhaemophilia(5-40%ofnormalclottingfactorlevel).

Allbabiesarebornwithlowlevelsofsomefactors,e.g.factorII(2),VII(7),IX(9)andX(10)thatgraduallyincreaseoverthefirst6monthsoflife.IfyourchildhasbeentestedatbirthandshowslowerlevelsoffactorIXthannormal,theirfactorlevelswillberetestedat6to12monthsofageforamoreaccurateresult.

Inmostcases,familieswithahistoryofhaemophiliatendtohavesimilarclottingfactorlevelsamongthemalesintheirfamily.

However,thefactorlevelsinfemaleswhocarrythegeneareunpredictableandcanvarybetweenfemalefamilymembers.Afamilywithahistoryofseverehaemophiliaamongthemalesmayhaveonedaughterwithmildhaemophiliaand another daughter who carries the gene but has no bleeding symptoms.


CHAPTER 2 2.7

Other bleeding disordersHaemophiliaisjustonetypeofinheritedbleedingdisorder.ThereareanumberofotherinheritedbleedingdisordersincludingVonWillebranddisease,rareclottingfactordeficienciesandinheritedplateletdisorders.

Von Willebrand disease (VWD)Von Willebrand disease (VWD) is the most common inherited bleeding disorderworldwide.BleedinginpeoplewithVWDusuallyinvolvesthemucousmembranes,thedelicatetissuesthatlinebodypassagessuchasthenose,mouth,uterus,vagina,stomachandintestines.ManypeoplewithVWDhavebleedingsymptomsthataremild,suchasbruisingeasily,nosebleeds,heavyperiods,orprolongedbleedingaftersurgery.However,somehavemoderateorsevereVWD.ThesymptomsofsevereVWDaresimilartoseverehaemophilia,withbleedingintothemusclesandjoints.WithallformsofVWDandlevelsofseveritytherecanbe bleeding problems.

Rare clotting factor deficiencies and platelet disordersThere are other bleeding disorders caused when the body does not produce enoughofaspecificcertainclottingfactor,orwhenthefactordoesnotworkproperly.Thesedisordersareknownasrareclottingfactordeficienciesandareveryuncommon.

RareclottingfactordeficienciesincludefactorI(1),II(2),V(5),VII(7),X(10),XI(11),orXIII(13)deficienciesandcombinedfactorV(5)andfactorVIII(8)deficiency.

Inplateletfunctiondisorders,theplateletplugdoesnotformproperly,leadingto a tendency to bleed for longer than normal or bruise easily. Since platelets havemanyrolesinbloodclotting,plateletfunctiondisorderscanrangefrommildtosevere.ExamplesofinheritedplateletfunctiondisordersincludeGlanzmannthrombastheniaandBernard-Souliersyndrome.

Parentswhohavechildrenwiththesetypesofbleedingdisordersmayhave similar experiences to parents of children with haemophilia.

For more information about VWD and other rare clotting factor deficiencies and platelet disorders, contact Haemophilia Foundation Australia or visit www.haemophilia.org.au


2.8 CHAPTER 2

Understanding how children inherit haemophilia

Haemophilia is an inherited condition and occurs in families. It is caused by a mutation (change or alteration) in the factor VIII or IX gene.

How did my child get haemophilia?Everypersonhasmillionsofcellsthatmakeuptheirbody.Atthecentreofeachcell are 46 chromosomes arranged in pairs. The chromosomes contain the person’sgeneticinformationor‘genes’,whichdeterminetheperson’sindividualcharacteristics,suchasthecolouroftheirhairortheireyes.

EveryonehasthegenesresponsibleformakingfactorVIIIandfactorIX.Thesefactors are necessary for blood to clot.

Haemophilia is caused by a mutation (change or alteration) in the factor VIII or IX gene. This altered factor VIII or IX gene affects the way that that the factor VIII or IX is made so that it might be missing or not enough is made for blood to clot properly. It is often called the ‘haemophilia gene’.


CHAPTER 2 2.9

Genemutationisanormalpartofnature.Therearemanygenealterationsthatleadtohaemophilia,thoughfamiliesinheritthesamegenealteration.Thespecifictypeofgene alteration also affects the symptoms that people with haemophilia experience.

Infamilieswithahistoryofhaemophilia,thegenealterationoccurredatsome pointinpreviousgenerations.Itisthenpassedonfromparenttochildthrough the generations. Examining the family tree may help to identify where this change occurred.

What if there is no obvious family history of haemophilia?Aroundonethirdofchildrenbornwithhaemophiliadonothaveanobvious family history of the disorder.

Inthesecases,thegenealterationmayhaveoccurredinarecentgeneration duringreproduction.Itmaybeappearingforthefirsttimeinthisfamilyinthe childorinthechild’smother–orsometimesthechild’sgrandmother.Thealteredgenemayhavebeenpasseddownthecurrentgenerationsfrommothertochild, without anyone realising until the child was diagnosed with haemophilia.

Haemophilia and the X chromosome Everyonehasapairof‘sex’chromosomes that determine their sex. Each parent contributes one of these chromosomes to their children.

Femalesalwayshavetwo X chromosomes (XX pair): one X chromosome is inherited from eachparent.Maleshaveone Xchromosome,whichtheyinheritfromtheirmother,andoneYchromosome,whichtheyinherit from their father (XY pair).

XY XX

XY XY XX XX

Normal inheritance pattern for X and Y chromosomes


2.10 CHAPTER 2

Foreverychildanycouplehas,therearefourpossiblecombinationsofchromosomes. These are shown in the ‘Normal inheritance pattern’ diagram.

ThegenesformakingfactorVIIIorIXarelocatedontheXchromosome.An X chromosome with the altered gene causing haemophilia can be passed from parent to child.

Father with haemophiliaA male with haemophilia carries the altered gene on their X chromosome.

As fathers only pass on the Ychromosometotheirsons,none of the sons of a man with haemophilia will inherit the condition.

However,fatherspassonthe X chromosome to their daughters. If their father hashaemophilia,allofhisdaughters will inherit the altered gene from him and will carry the gene causing haemophilia. When putting together a family historyofhaemophilia,daughters whose father has haemophilia are described as ‘obligate carriers’ as they will always inherit the gene from their father.

or has an X chromosome with the “haemophilia” genetic alteration.

or has an unaltered X chromosome.

Haemophilia genetic inheritance

XY XX

XY XY XX XX

FATHER MOTHER

When the father has haemophiliaand the mother is unaffected

None of the sons will have haemophilia.All of the daughters will carry the gene. Some might have symptoms or have haemophilia.


CHAPTER 2 2.11

Mother who carries the geneMothers pass on one of their X chromosomes to their children.

If the gene alteration responsible for haemophilia is located on one of the mother’sXchromosomes,thereisa50percentchanceateachbirththatany of her children will inherit this gene alteration.

If her sons inherit the gene alterationtheywillhavehaemophilia.

If her daughters inherit the gene alteration they will carry the gene. Some girls willhavenormalfactorlevelsandwillnothavebleedingsymptoms. Other girls willhavelowfactorlevelsandwillhavehaemophilia.

XY XX

XY XY XX XX

FATHER MOTHER

When the mother carries the altered gene causing haemophilia and the

father is unaffected

There is a 50% chance at each birth that a son will have haemophilia.

There is a 50% chance at each birth that a daughter will carry the gene. Some might have symptoms

or have haemophilia.

or has an X chromosome with the “haemophilia” genetic alteration.

or has an unaltered X chromosome.

Haemophilia genetic inheritance

Will my child’s children have haemophilia too?Oncehaemophiliaappearsinafamily,thealteredgeneispassedfromparents to children through the generations following the inheritance pattern explained inthe‘HaemophiliaGeneticInheritance’diagrams.

Sometimesitcanseemlikehaemophiliahasskippedageneration.Ifsonsin onegenerationhavenotinheritedhaemophilia,butsomeorallofthedaughterscarrythegene,andsomeoftheirchildrenhavehaemophilia,itmayseemthathaemophiliahasskippedageneration.

Haemophilia in girlsWhile most people diagnosed withhaemophiliaaremale,somefemalesdohavehaemophilia or bleeding symptoms. Most females withhaemophiliahavemildhaemophilia,butasmallnumberhavemoderateorseverehaemophilia.Therearealsosomefemaleswhohavefactorlevelsatthelowerrangeofnormalbutwhoneverthelessexperience abnormal bleeding.

MostfemaleswhohaveonehaemophiliaXchromosomeandcarrythegenedonothavehaemophilia.ThisisbecausetheyhaveasecondXchromosometogenerateenoughclottingfactorintheirblood.Somefemalesdo,however,havebleedingsymptomsfromhaemophilia,suchasheavyperiods,easybruising,poorhealing,prolongedbleedingafterchildbirthandbleedingfollowingsurgery,medical or dental procedures or trauma.

Inrarecases,theymayhavemoderateorseverehaemophiliaandalsohavebleedingintotheirjointsandmuscles.


2.12 CHAPTER 2


CHAPTER 2 2.13

ItisrecommendedthatallgirlsandwomeninafamilywithhaemophiliavisittheHaemophiliaTreatmentCentre(HTC)atleastoncetohavetheirfactorlevelstestedanddiscusstheirindividualissues.Iftheyhavelowlevelsandthereisariskofbleeding,atreatmentplanwillbeneeded.Thisisparticularlyimportanttodobeforeayounggirlstartsmenstruatingorbeforesurgeryordentalwork.IfyouoryourdaughtersarenotalreadypatientswiththeHTC,speaktoyourfamilydoctorso that they can arrange a referral to a haematologist at the HTC.

Why do bleeding symptoms occur in females?Bleedingsymptomsfromhaemophiliausuallyoccurinfemalesbecauseofaprocesscalled‘lyonization’.Ineachcellinafemale’sbody,oneofhertwoXchromosomesisturnedofforinactivated.WhichXchromosomesinafemale’sbodywillbeturnedoffappearstoberandom,butoncetheyareturnedoff,theXchromosomes will not be turned on again in her lifetime.

IftheXchromosomewiththealteredgeneisturnedoff,thatparticularcellwillproduce clotting factor VIII or IX. If the X chromosome with the unaltered gene is turnedoff,thatcellwillexpressthealteredgeneandfollowitsgeneticinstructions:itwillnotproduceclottingfactorortheclottingfactoritmakeswillnotworkproperly.AfemalewithlowclottingfactorlevelshashadmoreofherunalteredXchromosomesturnedoff,whichiswhyshemayexperiencebleedingsymptoms.Thisalsoexplainswhyafemalemayhavedifferentbleedingsymptomstothemales in her family with haemophilia.

You can ask your haematologist at your HTC if your daughter’s factor levels needs to be tested.


2.14 CHAPTER 2

Genetic testingAnormalfactorVIIIorfactorIXleveltestwillnottellyouwhetheryourdaughtercarriesthealteredgenecausinghaemophilia.Somegirlsandwomenmayhavenormalfactorlevels,butstillcarrythegene.

Talk to your HTC about genetic testing for your daughter. There are a few issues to consider and many people find that these tests give them a lot to think about. Your HTC can help with information and advice about genetic testing and can provide a referral to a genetic counsellor, if needed.

For more information on haemophilia in females, visit www.haemophilia.org.au

Deciding whether to having more childrenChoosingtohavemorechildrenisaverypersonaldecisionthatinvolvesconsideration of:

• youandyourpartner’spersonalfeelingsandbeliefs• yourfamily’slifestyle• howyoudealwithhaemophilia• yourreligion• familypressures• howmanychildrenyoualreadyhave• yourchanceofhavinganotherchildwithhaemophilia• otherfamilymembers’experienceswithhaemophilia.

Youdon’thavetomakethisdecisionalone.Thereissupportavailabletoyou,including your HTC and genetic counsellors.

See the ‘Who can I talk to’ section in this chapter for information on the support available to you.


CHAPTER 2 2.15

If I have another child, will they have haemophilia?Whetherotherchildrenwillhavehaemophiliadependsonwhenthegeneticalteration was introduced into your family.

Ifthisisthefirsttimehaemophiliahasappearedinyourfamily,youmaywanttohaveatesttodeterminewherethegeneticmutationoccurred.Testsusuallyinvolvetestingothermembersofyourfamily.

Where there has been a genetic alteration (spontaneous mutation) in your child alone,thenyourotherchildrenmaynotbeaffected.

If you have a son with haemophilia: If haemophilia has appeared in the mother’s extendedfamilybeforeyourson’sdiagnosis,themotherwillcarrythegene. If there is no family history of haemophilia there is still a chance the mother may carry the gene and further tests are needed to determine this. If the mother carries thegene,thereisa50percentchancewitheachpregnancythatotherchildrenthatyouhavewillinheritthegene.

If you have a daughter with haemophilia,itwilldependonwhethersheinherited it from her mother or her father. If your daughter inherited the gene fromhermother,thereisa50percentchanceateachfuturebirththatanothersonwouldhavehaemophiliaoranotherdaughterwouldcarrythegene.Ifyourdaughterinheritedhaemophiliafromherfather,menwithhaemophiliapassthe gene on to all their daughters but not to their sons. Therefore all your other daughterswouldcarrythegenebutnoneofyoursonswouldhavehaemophilia.Ifyouhaveanotherdaughterwhocarriesthegeneshemayormaynothavebleedingsymptomsandhavehaemophilia.

The ‘Haemophilia Genetic Inheritance’ diagrams in this chapter will help you understand your chance of having another child with haemophilia.


2.16 CHAPTER 2

Options to considerTherearemanydifferentoptionsforcoupleswantingtohavemorechildren. Tohelpsortthroughtheoptions,youmightdiscusssomeofthefollowingquestions with your partner:• Howwouldyoufeelabouthavinganotherchildwithhaemophilia?• Howwouldyoufeelaboutnothavinganymorechildren?• Wouldyouconsideradoptionorfostercare?• Wouldyouconsiderhavinganantenataltestat12weeksto determinewhetheryourchildhashaemophilia?

• Wouldyouconsiderterminationofpregnancyifthefoetusismale orthetestingshowstheyareaffectedbyhaemophilia?

• Howwouldyoufeelaboutusingin-vitrofertilization(IVF)and pre-implantation testing to ensure that the eggs implanted donotcontainthehaemophiliagene?

Someoptionsmaynotseemrighttoyouforpersonal,moral orreligiousreasons.Someoptionsmaynotbeavailableinyourarea.

Thechoicesyoumakemightbedifferentdependingonyourexperience ofhavingchildrenwithhaemophiliaorhaemophiliainyourfamily.

Who can I talk to?While the decision ultimately must be yours and your partner’s,therearepeopleyoucantalktowhocanprovideyouwith information and help put thingsinperspective,including:

• Haemophilia Treatment Centre (HTC) YourHTCteamisalwayshappytotalkwithyou.Theycanexplaintheoptionsavailabletoyouandputyouintouchwitharangeofservices,fromtestingtofamily planning and genetic counselling.

It is important that the decision you reach is yours and is right for you and your family.

PARENTTIP


CHAPTER 2 2.17

• Genetic counsellor Ageneticcounsellorcanworkwithyouandprovideinformationaboutthevariousoptionsforhavingmorechildren.Theycanalsohelpwithfindingoutabout carrier status.

Geneticcounsellorstalkthroughtheoptionsavailable,provideinformationonthevariousoptions,listentowhatyourfeelingsandbeliefsareandactasa‘soundingboard’whileyoumakeyourdecision.

• Haemophilia Foundations Haemophilia Foundations understand the deeply personal nature of this decision.YourlocalFoundationcanprovidesupportbutitwillnottrytomakeyour decision for you. Your local Foundation can also put you in touch with a rangeofpeoplewhocanassistwithyourdecisionmaking.

• Friends and family Trusted friends and family can offer you guidance and support.

• Other families Talkingwithotherfamilieswhohavefacedthisquestion,andfindingouthow

they made their decision may help you. While the decision they made may not berightforyou,understandingtheiropinionscanprovideyouwithclarity.

Your HTC can advise you and put you in touch with counselling services. Your local Haemophilia Foundation can help you talk with other families.

ReferencesAustralianHaemophiliaCentreDirectors’Organisation.GuidelinesforthemanagementofhaemophiliainAustralia.Melbourne;Canberra:AHCDO;NationalBloodAuthority,2016.<https://www.blood.gov.au/haemophilia-guidelines>

AustralianBleedingDisordersRegistry(ABDR)AnnualReport2015-16.Canberra:NationalBloodAuthority,2017.<https://www.blood.gov.au/system/files/abdr-annual-report-2015-16-final.pdf>

WorldFederationofHemophilia.Hemophiliainpictures.Montreal:WFH,2005.<https://www1.wfh.org/en/index.html>


2.18 CHAPTER 2

AcknowledgementsSome information and illustrations in this resource were originally published by the WorldFederationofHemophilia(WFH)andhavebeenadaptedwithpermission.The WFH is not responsible for any inaccuracies in content different from the content of the original English edition.

ThisresourceistheresultofasubstantialreviewandadaptationofHaemophilia: for parents whose child has recently been diagnosed with haemophilia,originallypublished byHaemophiliaFoundationAustraliain2004,withrevisionsin2014.

ThecontentinthisresourcewasredevelopedbytheCentreforCommunityChildHealth at The Royal Children’s Hospital and the Murdoch Children’s Research Institute for Haemophilia Foundation Australia.

Thisresourcewasreviewedby:DrMoanaHarlenfromAustralia/NewZealandHaemophiliaSocialWorkers’andCounsellors’Group;JanineFurmedge,AnneJackson,SiewLee,JoannaMcCosker,RobynShoemark,JamesSladeandHelenStarostafromAustralianHaemophiliaNurses’Group;AuburnMcIntyre,AlisonMorris,WendyPoulsenfromAustralianandNewZealandPhysiotherapyHaemophiliaGroup;DrChrisBarnes,DrJulieCurtinfromAustralianHaemophiliaCentreDirectors’Organisation;SharonCarisandSuzanneO’CallaghanfromHaemophiliaFoundationAustralia;SandyBreit,griefandlosscounsellor;andbleedingdisordercommunityrepresentativesfromHFAParentsConsumerReviewGroup.

ThiseducationresourcewasfundedbythedonationsofmanyindividualstoHaemophiliaFoundationAustraliaandaneducationgrantfromPfizer.

©HaemophiliaFoundationAustralia,October2017www.haemophilia.org.au This resource may be printed or photocopied for education purposes

Important noteThisresourcewasdevelopedbyHaemophiliaFoundationAustraliaforeducationandinformationpurposesonlyanddoesnotreplaceadvicefromatreatinghealthprofessional.Alwaysseeyourhealthcareproviderforassessmentandadviceaboutyourindividualhealthbeforetakingactionorrelyingonpublishedinformation.

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Understanding haemophilia · Understanding haemophilia CHAPTER 2 2.1 CHAPTER 2 Haemophilia is an inherited bleeding disorder where blood doesn’t clot properly. It is caused when