HEMOPHILIA

Introduction:

In general term hemophilia describes a group of inherited blood disorders in which there is a life long defect in the clotting mechanism of the blood. A hemophilic person does not bleed more profusely or bleed faster than normal- he simply bleeds longer unless treated. Hemophilia is usually not associated with higher incidence of any other congenital abnormality.

The incidence is about 1:10000 males birth and all races, religions and socioeconomical groups are affected. It was estimated in 1990 that there were 350, 000 individuals with hemophilia world wide with 80% or 280, 000 without treatment.

The disease is incurable, but if the baby is early diagnosed and treated early with adequate replacement of the deficient coagulation factor, the baby can expect to lead a near normal life, to share responsibilities both for himself and future generations and live to old age.

There are several clotting ingredients in the blood and when one of the clotting ingredients in the blood is defective, the clotting mechanism does not work properly.

Normally the ingredients, which are called factors, act like a row of dominoes topping against each other to create a chain reaction. If a factor does not work this chain reaction canít proceed.

There are two major types of hemophillia differ only in the clotting factor involved: Factor viii (Classical hemophilia, Hemophilia A) and Factor ix (Christmas disease, Hemophilia B). It is important to know which factor is abnormal since therapy is based on replacing the specific affected factor. Hemophilia B is also called Christmas disease, as Christmas was name of the first person diagnosed with the condition. Hemophilia A is five times more common than hemophilia B.

Both types of hemophilia share the same symptoms and inheritance pattern- only blood test can differentiate hemophlia. Except in very rare case hemophilia A and B affect only males. The disease is also classified into levels of severity by measuring the amount of the affected factor in the blood: e.g.- mild, moderate and severe. Within any given family all hemophilic are of the same type and severity. The severity of hemophilia is related to the degree of deficiency of the relevant clotting factor in the blood. When there is less than 1% of the normal factor activity present, the condition is described as "Severe". Between 1% and 5% of normal activity is classified as "Moderate" and greater than 5% of normal activity is described as "Mild". Normal activity levels range between 50 and 200%. The average activity level in the population as a whole is 100%.

 

 

 

Inheritance:

Hemophilia is an inherited condition. It is termed as a " Sex linked recessive" condition. This means that while only males have the condition, it is passed through females in the family.

The cells, which make up our bodies, are programmed from instructions from our mothers and fathers. These instructions are called genes. The genes are carried on structures called chromosomes. Two of the chromosomes determine the sex of the individual.

 

They are called X and Y. Females have two X-chromosomes (XX) and males an X and Y-chromosomes (XY) The genetic defect that causes hemophilia is on X-chromosomes.

Therefore the daughter of a man with hemophilia must inherit his X-chromosomes and be a carrier of hemophilia.

The carrier daughter will not have hemophilia herself because the other normal chromosome that she has inherited from her mother provides the necessary instructions for making the active factor VIII.

Clinical Features:

It varies with the clinical severity of disorder markedly between families, but within a kindred all affected members will have essentially the same base line levels of F VIII or F IX activity. The normal range of factor activity varies from 50-150%.

Severe Hemophilia (less than 1% Factor VIII or Factor IX)

Prolonged or repeated bleeding may occur at one or more sites at a time an trauma which is so slight as to be unrecognised may produce bleeding which therefore appears to be spontaneous. Bleeding is mainly internal producing haemorrhage into joints (haemarthroses), muscle and soft tissues, other organs or central nervous system Bleeding episodes may be noted in early infancy, for example after circumcision Bleeding in Knee, elbow, ankle joints is very common. Bruising is common and often lumpy. It may be sufficiently extensive to raise the suspicion of child abuse. Joint and muscle bleeds occur when crawling and walking start. Swelling or reluctance to use a limb is often signs of joint or muscle bleeds at this age. Bleeding from mouth is tongue is also common at this age, and is often associated with falls.

Recurrence of untreated or inadequately treated bleeding into joint leads to early disability from synovial and joint surface damage. Secondary muscle wasting will occur and the resulting weakness contributes to recurrent bleeding .If one joint has recurrent bleeding it is referred to as a "target joint".

Moderate Hemophilia (>1-5% Factor VIII or Factor IX)

Bleeding episodes are less frequent and more related to trauma. There are fewer handicaps. Bleeding also occurs with all forms of surgery and dental extraction. Drugs should be given orally, rectally or intravenously and not intramuscular route.

Mild Hemophilia (>5% Factor VII or Factor IX)

Many people are diagnosed late in life after surgical or dental procedure or after trauma when abnormal bleeding occurs. They may also present with muscle or joint bleeds following significant injury.

Children with hemophilia should be encouraged to lead a normal life but they and their parents do need to be aware of potential dangers of trauma.

Diagnosis:

The first step in diagnosis is a detailed personal and family history with specific questions about increased bruising (both superficial and deep), bleeding after circumcision, bleeding after dental extraction or tonsillectomy and occurrence of bleeding episodes in

Close relatives. In fact in any person with prolonged or unexplained bleeding the possibility of hemophilia should be considered and test done.

The second step is the performance of tests for haemostats: bleeding time activated partial thromboplastin time (APTT) and prothrombin time (PT). The bleeding time is usually normal, as platelet function is unaffected in hemophilia. Depending on the sensitivity of the test, the APTT, a relatively simple test should be prolonged with factor levels less than 30%.

At the initial investigation and at the regular reviews, blood should be taken for factor inhibitor screening and for hepatitis and human immunodeficiency virus (HIV) testing.

Treatment:

Replacing the missing factors treats both hemophilia A and B. The materials used including whole blood transfusion, fresh frozen plasma, cryoprecipitate or concentrate factor VIII or IX.

All of the materials must be given by a needle directly into the hemophilic vein, if given orally, the clotting factors would be digested by the stomach and becomes useless, if injected under the skin or into the muscle, it would not be well absorbed into the blood stream where it is needed to interact with the rest of the clotting systems to stop the bleeding.

Initially these injections have to be given by a nurse or doctor in the hospital. As the child grows, his parents learn to give the injections themselves at home. Eventually the person with hemophilia learns to give his own injection, usually when he is a teenager.

After a bleed has begun, earlier an injection is given the better. Blood clotting is then made normal and the bleeding episode ceases. People learn to seek treatment immediately they know that a bleed has started. This is called on-demand therapy. There is another sort of treatment, called prophylaxis, in which injections are given regularly, usually two or three times a week, in order to prevent bleeding occurring in the first place.

The active lives of the clotting factors used in the treatment varies. For instance, within about 12 hours half of the clotting activity of the injected factor VIII will have disappeared from the blood stream, so the injections have to be repeated.

When given promptly one injection usually stops bleed. Once bleeding stops, any pain ceases and the person can return to normal activity straight way Quick treatment also means that permanent damage to joints and muscles is avoided.

Now a dayís both factor VIII & IX are provided in the form of freeze -dried powders sealed in small glass bottles. The powder is mixed with sterile water and the injection is given by syringe. Now there are two sources of the factors. The commonest source is human blood plasma. There is either collection directly from donor or is separated from other constitutes of blood shortly after donation. Many donations are pooled together and the component parts separated out by a process called fractionation to produce pure clotting factors, which are then, freeze dried. Most recently, synthetic factor VIII has been produced using a technique called recombinant technology. In future this synthetic factor VIII may well become the usual form of therapy for people with hemophilia. This is because the synthetic product has a greatly reduced risk of containing the viral contaminants that may be present in human blood. In addition it will not be subject to the potential supply shortages associated with human blood products.

People with mild hemophilia A are nowadays treated with a drug called desmopressin or DDAVP rather than blood product. Desmopressin stimulates thebody to produce normal factor VIII in these people.

An adequate dose of factor concentrate depends on plasma volumes, the resting factor level, activity of the material used and the " in vivo" recovery material.

Precautions in Hemophilia:

1.Aspirin is strictly contraindicated in any one with bleeding disorders. Aspirin has a side adverse effect on platelet function, and an inflammatory effect on gastric mucosa, which may result in haematemesis.

2.Non- steroid anti- inflammatory drugs (as used in arthritic conditions) should be prescribed with caution in hemophilia because of their aspirin- like effects. They should only be taken after food, and stopped in the event of indigestion.

3.Intramuscular injections are contraindicated because they may provoke severe intramuscular bleeding with subsequent cyst formation or fibrotic scarring.

Oral, rectal, subcutaneous or intravenous medications are alternatives.

4 Whilst immunisation routinely given by intramuscular injection is safe provided digital pressure is applied to the injection site for 5 minutes, it is probably safer to give all immunisations subcutaneously.

5 Activities and sports are positively encouraged in hemophilia because it is recognised that a healthy musculoskeletal system helps prevent bleeding. Only those sports likely to result in head injury (boxing and rugby football are the main examples) should be actively discouraged.

Hemophilic patients in Nepal:

Nepal Hemophilia Society is a registered NGO, recognised by World Federation of Hemophilia in 1992.

The main objects of the society are: -

  1. To introduce community about hemophilia and its management
  2. To educate hemophilic patients with up to date information
  3. To provide diagnostic facilities and counselling.
  4. To make treatment available
  5. To organise and participate the workshop, meeting and seminars concerning hemophilia
  6. To publish booklets, pamphlets, leaflets to provide informationís.
  7. To provide training to the interested persons
  8. To motivate the blood donors to donate more blood so that fresh frozen plasma and cryoprecipitate can be extracted in adequate amounts.

At present there are 96 hemophilic patients registered to the society (74-factor VIII, 21 factor IX and 2 factor X). Four patients died of brain haemorrhage.

Unfortunately here in Nepal the patients are mostly dependent on blood products like fresh frozen plasma or cryoprecipitates which does not provide sufficient amount of

Missing factors as the commercially available factor concentrates are beyond the reach of the patients (1vial costs approx. 400 US $). As most of the products (blood products)

Is not gone viral inactivation procedure, it is essential that donors are carefully selected by questionnaire and interview and individually tested for hepatitis virus and HIV.

Due to inadequate and improper treatment few patients have already developed severe degree of bigger joint damage and they badly need to go for surgery like Total Joint Replacement.

Surgery in haemophilia requires through preparation and should only be carried out in hospitals where staffs have the experience to manage the patient with hemophilia safely.

Before surgery the patient should be screened for the presence of inhibitors (an antibody developed against the clotting factor). Sufficient factors must be available to cover both the procedure and the postoperative period. The factor levels will need to be raised to > 60% and maintained there for at least a week after major surgery and at a somewhat lower level until healing is complete. Twice daily (for factor VIII) or daily (for IX) infusion will be needed in the immediate postoperative period. There must be a laboratory and personnel able to monitor factor levels. In a surgical situation patients with mild hemophilia need as much care and attention as patients with severe hemophilia, remembering that any complication of surgery usually requires additional therapy.

The hemophilic patients need comprehensive care as continuing supervision of all medical and social aspects affecting the patient as well as his family. The modern care is delivered by a team of professional physicians of various specialities like Haematologist, Orthopaedic Surgeon, Child Specialist, Dental Surgeon, Nurse, Social worker, Physical Therapist, Psychiatrist, Psychologist and Counsellor etc.

Through World Federation of Hemophilia , few doctors working in the Nepal Hemophilia Society have been able to receive special training for 6-8 weeks at different International Hemohpilia Centre ( IHTC) to treat the hemophilic patients in better way.

Till now Dr. B. L. Bajracharya - a Child Specialist has received training in Bangkok, organised by World Federation of Hemophilia in 1993. Similarly Dr. M. P. Shrivastava- an Orthopaedic Surgeon of the society has received special training at Tel Hashomer, Israel last year in May 1998 for treating hemophilic patient when required surgically.

Due to lack of skilled man power, lack of interest in treating the hemophilic patients when required surgically and of course non- availability of factor concentrates most of the patients are still being sent to Vellore, India. (Although few emergency operations have been performed at Kathmandu) for the treatment.

Now the society is in process of opening a National Haemophilia Care Centre and in providing the appropriate treatment to the patients in the country itself in near future with the help of local manpower, World Federation of Hemophilia and a surgical team from abroad.

Conclusion:

Haemophilia is congenital life long disorder. The goals of the treatment should be to minimise disability and prolong life, to facilitate general social and physical well being and to help each patient achieve his full potential.

So there are many reasons to be optimistic about the future for people with haemohpilia in Nepal and around the world. Now the treatment with blood clotting factors is as safe as it can be made.

Prophylaxis is being used increasing, and has had a dramatic impact on reducing disability through damaged joints.

Synthetic factor VIII an IX are now available in the market, and carry even smaller risks of viral contamination, and are potentially free of supply problems, at least in developing countries.

Finally, great advances have been made in genetics over the years. There is now the possibility that the use of gene therapy may be feasible at some time in the future to help to alleviate the severity of peopleís hemophilia.

 

Dr. M. P. Shrivastava

Consultant Orthopaedic Surgeon

NEPAL HEMOPHILIA SOCIETY

P. O. Box : 6046

Kathmandu, Nepal.

Tel: 00977- 1- 220608

Fax : 00977 - 1- 256105

E-mail: shyam@spanday.wlink.com.np

Thursday, 15 April 1999