An Introduction to RareBleeding & Platelet

Disorders

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 contained in this booklet come directly from peopleaffected by bleeding disorders. Pictures used with permission.

2

3

An Introduction to Rarer Bleeding Disorders

This is an introductory booklet for rarer factor and platelet disorders. Itshould be helpful for people directly affected by bleeding disorders andalso 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 lookforward to a normal life expectancy taking advantage of education,training, sport, employment and travel opportunities.

For more detailed information on general issues and other disordersplease see the other two booklets in the series: A GeneralIntroduction to bleeding disorders or An Introduction to haemophilia.

What are bleeding disorders?

Bleeding disorders are conditions, usually inherited, where the bloodfails to clot properly. These conditions are rare in the generalpopulation and around 24,000 people in the UK are diagnosed with one.Most literature on bleeding disorders focuses on haemophilia A and B(Factor VIII and Factor IX deficiency). However, there are rarer cases ofdifferent types of disorder. As many are very rare, there are often gapsin current knowledge and further research is still needed. This bookletaims to be a comprehensive introduction to what is known about eachdisorder and its treatment including:

Factor deficiencies I, II, V, VII, X, XI, XII and XIIIPlatelet disorders such as: thrombocytopeniaBernard-Soulier syndromeAlpha Granule Deficiency/ Gray Platelet SyndromeGlanzmann’s ThrombastheniaDense Granule Deficiency/ Delta Storage Pool Deficiency

This booklet is a brief introduction. If you would like more in-depthinformation on any of the issues mentioned here, please see one of ourother publications, look on our website, or get in touch with us by phoneor email.

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

How do you get bleeding disorders?

Most bleeding disorders are inherited, meaning they run in families.Rarely, it’s possible to develop or acquire a bleeding disorder, oftenbecause of another illness or condition.

The cells which make up our bodies are programmed withinstructions from our parents. These are the genes that hold the geneticinstructions for life. Unlike haemophilia A and B, most bleedingdisorders featured here are caused by genes which aren’t sex-linked.This means they affect both men and women equally. Many have whatis called an autosomal recessive pattern, meaning that both parentsneed to be carriers of the gene for a child to be affected with a certaincondition. However, many of the disorders we will cover here are not yetfully understood. If you would like more information on genetics andgenetic counselling, please see our General Introduction book.

(left) Typical patternwhen both parents arecarriers of a condition.

(left) Typical patternwhen an affectedperson has childrenwith a non-carrier.

For some disorders it is thought they can also follow a dominantinheritance pattern, where only one parent needs to be a carrier for thechild to be affected with a certain condition. If you are concerned aboutgenetics you might like to consider a referral for genetic counselling.

As they are often inherited in a recessive pattern, bleeding disordersseem to be more common in areas or groups of people where there hasbeen a tradition of marrying close relatives such as cousins, eitherrecently or in the past.

4

5

What are bleeding symptoms?

People have different symptoms, depending on the individual and alsothe type and severity of the disorder. The following are commonly seenin people with rarer bleeding and platelet disorders. Not everyone willexperience all of them.

‘My condition is rare (storage pool disorder), andinformation on the internet seems to be only

specialised medical essays. I sometimes feel a bitabandoned to be honest!’

· Nose bleeds (epistaxis) - are common in many disorders andespecially in young children.

· Easy bruising - young children with bleeding disorders oftenbruise easily and in places where other children normally wouldn’t(see our general booklet for more information on what to do).Many adults also bruise easily.

· Mouth bleeds - can also be common in children.

· Heavy periods - many women who are affected by or who arecarriers of bleeding disorders have heavy periods (menorrhagia)and may also have painful periods (dysmenorrhoea).

· Bleeding after injury, surgery, or after giving birth - canusually be managed with factor replacement.

· Joint & muscle bleeds - are less common with rarer bleedingdisorders and rare with platelet disorders.

· Miscarriage - some factor deficiencies may cause a higher thanaverage chance of miscarriage which can often be managed.

· Blood in urine - or other bodily fluids.

· Bleeding from umbilical cord - or stump in new-borns (withsevere cases only).

· Central nervous system (CNS) bleeds - such as in the brain orspine, these are very serious and may occur with some disorderslike Factor VII deficiency, in very severe cases.

· Small pinprick bruises (purpurae) - on the skin often occur withplatelet disorders.

6

Do I have ‘haemophilia’?Sometimes people use ‘haemophilia’ to mean any bleeding disorder.Strictly speaking it only means haemophilia A (factor VIII deficiency) andB (factor IX deficiency). You should find out exactly which bleedingdisorder you have in order to get the right information and treatment.You should also consider carrying a medic alert card or bracelet in caseof an accident or emergency.

People with rare bleeding or platelet disorders are also treated athaemophilia centres which will have the correct information andadvice for your condition. They are also welcome to use all the servicesof The Haemophilia Society, which is the national charity for all peopleaffected by bleeding disorders.

‘My son is 14 and has just been diagnosed with aplatelet disorder - in some ways it’s a relief to have a

name for it’

What treatment will I get?Your treatment will depend on the type and severity of your bleedingdisorder. If your bleeding symptoms are quite serious, you may need tobe treated with a specific factor replacement. As many of thesedeficiencies are very rare, specific factor products have not beendeveloped for all of them and you might need to be treated with freshplasma (frozen and thawed for infusion as required), which contains allthe clotting factors. This is particularly used for factor V deficiency andsometimes for factor XI deficiency.

Factor concentrates are isolated concentrates of your particularfactor, some of which contain 3 or 4 different factors. You may receivethis when needed (on-demand) or as a regular treatment to try toprevent bleeding (prophylaxis). Concentrates are normally administeredthrough an intravenous injection (infusion).

FFP or fresh frozen plasma is a yellow-coloured liquid. Plasma is thepart of the blood containing all the clotting factors and it is made fromdonated blood and blood products. This may be given if there is noconcentrate available for your factor deficiency.

Fibrin glue can sometimes be applied straight to a wound to help a clotstabilise.

7

Tranexamic acid can be taken in tablet form to help clots stabilise.

Desmopressin is a synthetic hormone which helps stop bleeding, andcan be given intravenously, under the skin, or sometimes as a nosespray. DDAVP is the trade name for the IV preparation.

Platelet transfusion is used when a more serious bleeding in peoplewith platelet disorders means that a transfusion of platelets may beneeded.

Contraceptive pills, coils, or implants can be very helpful for womenand teenage girls in treating heavy periods.

‘I found out I have Factor XI deficiency a while back buthave not been given very much info on it,

can you help?’

What can you do to prevent complications?By following the advice of your haemophilia centre you can learn tomanage your own condition and hopefully avoid some of the possiblecomplications of bleeding episodes.

The PRICE regime: Protection, rest, ice, compression and elevation isa good first-aid method for treating bleeds and swelling.

Physiotherapy: Access to specialist physiotherapy can be invaluable inhelping to prevent damage after bleeds. For example a physiotherapistmay be able to correct damaging changes to gait and weight-bearing.

Exercise: Exercise and staying at a healthy weight are stronglyrecommended for helping to strengthen the joints and muscles if theseareas are prone to bleeding.

Dental care: Looking after your teeth is really important for people withbleeding disorders, as dental work can cause bleeding problems.

Medic Alert: It’s a good idea to carry details of your condition on you incase of an accident or emergency.

It’s important that people with bleeding disorders don’t take aspirin inany form, as it interferes with clotting. Other substances such as non-steroid anti-inflammatories like ibuprofen, or certain Chinese herbs,and alcohol may also cause bleeding so be aware and check with yourcentre before using certain substances.

8

How does clotting happen?

Blood is made up of four parts: plasma, platelets, red blood cells andwhite blood cells. Clotting involves two of these.

Plasma is the liquid part of blood containing clotting factors.Platelets are small disc-shaped cells which when activated form abarrier over the site of bleeding to form a clot.

When you start to bleed, platelets are activated to form a clot over thearea. They are then stuck on with the help of von Willebrand’s factorand the coagulation cascade begins to act to stabilise the clot.

There are several known factors that are needed for blood to clot. Theseare written using Roman numerals: for example, factor two deficiency isFactor II and factor seven deficiency is Factor IX. When blood clots,many clotting factors act together to make the final clot. This issometimes known as the clotting cascade or coagulation.

When you have a factor deficiency, you are lacking one or more ofthese factors. It may be that you have reduced amounts or virtually noneat all. It only takes one to be missing for clotting to be affected. That’swhy you get bleeding symptoms like bruising, nose bleeds, internalbleeding and so on. When you have a platelet disorder you either havetoo few platelets to clot properly, or they are not working properly.

(left) Simplediagram ofthe clottingprocess;

(right) Whathappenswhen one

clottingfactor is

missing ordeficient

Fibrin clot formation

Platelet plug forms at site ofinjury

Platelets adhere to damagedvessel wall

9

A guide to rarer bleeding disordersIn the following part of this booklet we have provided brief summaries ofmost of the rarer bleeding disorders. If you would like more detailedinformation please contact the Haemophilia Society or your ownhaemophilia centre.

Factor deficienciesHaemophilia A and B are deficiencies of factor VIII (8) and factor IX (9)respectively. It is also possible to have a deficiency of other factors.This means that you do not have enough of a certain factor in your bodyfor blood to clot properly. In the most severe cases, people havevirtually none of a certain clotting factor at all.

As with haemophilia, factor deficiencies are treated by replacing themissing factor. However, single clotting factors are not available forevery condition. If this is the case you may be treated with plasma,which contains all the factors. As with haemophilia, replacement factoror plasma is given by intravenous infusion.

If you have a severe deficiency you may even take this as a prophylaxis,i.e. regular treatment to try to prevent bleeds from happening. You maystore your factor replacement at home and be able to take it on holiday,depending on the individual condition. For more minor bleeding you maybe treated with other forms of medication (see page 6).

Some factor deficiencies have a greater tendency to certain types ofbleeding, although each case is different. These summaries are roughguides only and symptoms vary from person to person.————————————————————————————–———-Factor I deficiencyAlso known as afibrinogenaemia (no factor I), hypofibrinogenaemia (lowfactor I levels) or dysfibrinogenaemia (when the factor I does notfunction properly). Fibrinogen is another name for Factor I.

Symptoms may include: bruising, nosebleeds, joint bleeds, mouthbleeds———————————————————————————–————-Factor II deficiencyAlso known as prothrombin deficiency, this is a very rare condition.

Symptoms may include: bruising, nosebleeds, bleeding after trauma,some muscle bleeds

10

————————————————————————————————Factor V deficiencyThis should not be confused with Factor V Leiden, a more commonthrombosis disorder where blood clots excessively. Factor VLeiden is not a bleeding disorder.

Note: Levels of Factor V are usually raised above the adult normalrange at birth and in the first few months of a baby’s life.

Symptoms may include: nosebleeds, mouth bleeds, bruising, heavyperiods, bleeding after trauma.—————————————————————————————–——-Factor V with factor VIII deficiencyThis condition of combined deficiencies usually requires that bothfactors be replaced. Symptoms are similar to those of mild haemophilia,but with added bleeding caused by additional FV deficiency .—————————————————————————————–——-Factor VII deficiencySymptoms may include: nose and mouth bleeds, heavy periods,bleeding after trauma. Spinal and intracranial (brain) bleeding is asignificant risk, especially during birth.

Note: Factor VII deficiency may also be linked to vitamin K deficiency,especially in new babies.————————————————————————————————Factor X deficiencySymptoms can include: bruising, joint and muscle bleeds, nosebleeds,blood in urine, bleeding after trauma, bleeding from the umbilical cord,gastrointestinal bleeding.

Factor X deficiency is also very rare.————————————————————————————————Factor XI deficiencyFactor XI deficiency used to be known as Haemophilia C andsometimes is still referred to in this way.

Note: FXI deficiency is one of the more common rare bleeding disordersand so more information is available on this condition. Around 8% ofpeople from Ashkenazi Jewish backgrounds have the disorder.

Symptoms can include: bleeding after trauma, heavy periods, mouthbleeds.

11

————————————————————————————————Factor XII deficiency does exist but does not appear to causebleeding problems.————————————————————————————–———-Factor XIII deficiencySymptoms can include: bruises, muscle bleeds, spinal andintracranial bleeds, bleeding after trauma and slow wound healing.————————————————————————————————Acquired factor deficiencies can also occur through other conditionssuch as leukaemia, liver disorders, or vitamin K deficiency. Thesymptoms and treatment of acquired disorders are similar to thosewe’ve described when a condition is inherited. In many cases they canbe resolved or go into remission.

‘I would just like to thank you for all the information. Ihave shown my partner and he was amazed at howmuch information there was on my condition (FXI)’

Platelet DisordersA platelet is a small cellthat makes up part ofyour blood. When youare hurt or bleeding,platelets are stimulatedto stick to the damagedblood vessel wall andclump or aggregatetogether. Certainproteins on the surfaceof the platelet areneeded to stimulate thisaction. When the plateletis activated there aregranules inside whichrelease proteins andother substances to helpclotting. Many plateletdisorders are causedwhen these steps don’twork properly.

12

Platelet disorders occur either when the number of platelets is low orwhen the platelets do not function correctly because of their size orshape. Similar bleeding symptoms will often be observed as in peoplesuffering from factor deficiencies, such as bruising, nosebleeds andproblems with heavy periods for women.

Platelet disorders also commonly cause wounds to bleed for a long timeand may cause small pinprick bruises, or purpurae, on the skin whichare not a feature of clotting factor defects. Joint and muscle bleeds arenot usually seen with platelet disorders.

Thrombocytopenia means having a low platelet count. This conditionis often acquired through having certain illnesses, but it can more rarelyalso be inherited. It is often characterised by small rash-like bruisescalled purpurae.

ITP (immune or idiopathic thrombocytopenic purpura) - this is one of themost common causes of a low platelet count. It’s an acquired (i.e. notinherited) disease that occurs when the immune system attacks anddestroys the body’s own platelets.

TTP (Thrombotic thrombocytopenic purpura) - when the formation ofsmall clots in the blood causes the platelets to be destroyed. Thisdisorder triggers too many clots to form and does not result in bleeding.This can be inherited and is linked to the dysfunction of vonWillebrand’s factor.

There are several inherited conditions that can also cause a low plateletcount along with other symptoms. These conditions are very rare andmay cause other serious symptoms as well as bleeding problems.

Disorders of platelet functionFor help in understanding your blood test results, please see our bookletA General Introduction to bleeding disorders.

Bernard-Soulier syndromeThis rare disorder is caused by a deficiency on the surface of theplatelet which means platelets do not clump together effectively to formclots.

13

Blood tests show:- a prolonged bleeding time- a low platelet count- that the platelets appear larger than normal when seen through a

microscope- that the platelets do not clump together in response to ristocetin (a

substance used to test clotting)

Dense Granule Deficiency/ Delta Storage Pool DeficiencyThere is a lack of storage granules for certain substances needed fornormal platelet activation. Their absence slows down the clottingprocess.

Bleeding time is sometimes longer than normal. A platelet aggregationtest shows an abnormal pattern. Examination of the platelets using anelectron microscope shows an absence of dense granules.

Some people with this disorder may also have other conditions whichcause abnormalities in hair colour and vision and make them moreprone to infection.

Glanzmann’s Thrombasthenia.Glazmann’s is caused by a deficiency of a protein on the surface of theplatelet, which means that platelets fail to form a plug at the site of aninjury.

Blood tests show:- The platelet count is normal- that bleeding time is much longer than normal- that the platelets do not clump together at all

Alpha Granule Deficiency/ Gray Platelet SyndromeThere is a lack of important proteins in the granules inside the platelet,which slows down the way in which platelets stick to a wound and clumptogether.

Bleeding time is usually long and the platelet count may be low. A test ofplatelet aggregation shows some abnormalities. Seen through amicroscope, platelets show an absence of granules and look grey incolour because of this.

What’s next for rare bleeding disorders?

There are many reasons to be optimistic about the future for people withbleeding disorders. For people who receive plasma-derived treatmentsor platelet transfusions, improvements to safety are continually reviewedand developed. Donors are carefully screened and blood products aretreated with a range of methods designed to get rid of viruses that maybe present. Blood and blood products can now be said to be safer thanever. There is also the possibility of developing more recombinantfactors for other deficiencies.

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 andB is still at an early stage, but gene therapy is a very encouragingprospect for the future.

‘Don’t let something like this hold you backbecause later you will regret it’

(Above) Characters from our youth website Young Bloods; some withrarer disorders; (Below) The Haemophilia Society works for everyone

affected by bleeding disorders.

14

15

ResourcesThe Haemophilia Society produces a range of resources includingDVDs, publications, and online information. For an up-to-date list plusdownloads, 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 Haemophiliaoffers a searchable database onftreatment centres worldwide.www.hemophilia.ca—the Canadian Hemophilia Society’s website hasa range of useful downloads, especially for rarer disorders.www.ukhcdo.org –the website of the UK Haemophilia CentreDoctors’ Organisation, where you can find patient information, servicespecifications, and lists of UK haemophilia centres.www.medicalert.org.uk - a registered charity offering a range of medicalert jewellery and tags.www.bpl.co.uk - the UK Blood Products Laboratory produce a range ofuseful booklets, including some on rarer disorders.

For rarer disorders:www.pdsa.org - US-based platelet disorder support associationwww.ttpnetwork.org.uk - support group for TTPwww.itpsupport.org.uk - support group for ITPwww.bernardsoulier.org - site dealing with Bernard-Soulier syndromewww.glanzmanns.com or www.glanzmanns.cwc.nethome.earthlink.net/~deltaspd/index.html - storage pool disorderwww.rbdd.org - international database on rare bleeding disorders

Haemophilia Society Publications:An Introduction to haemophilia (2008)A General Introduction to bleeding 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.

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 Paula Bolton-Maggs,Dr Mike Richards, Ian D’Young, Tony Nugent

Our thanks also go to the World Federation ofHemophilia and the Canadian Hemophilia Society whokindly gave permission for the reproduction of theirImages.

The Haemophilia Society 2012 (reprint)

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