THALASSEMIA N ME

Thalassemia is an inherited blood disorder which is caused by an abnormal gene. A person with Thalassemia is unable to produce normal haemoglobin in the blood.

Haemoglobin carries oxygen in the blood from the lungs to all parts of the body. When the body is unable to produce normal haemoglobin, the resulting low haemoglobin levels give rise to anemia.

Thalassemia is passed on from parent to child and can affect both males and females. In, Singapore about 3% of the population are carriers of the Thalassemia gene.

WHAT ARE THE TYPES OF THALASSEMIA ?

There are two types of Thalassemia:

(l) Thalassemia minor (Thalassemia trait)

(ll) Thalassemia major.

A person who has inherited one Thalassemia gene is said to have Thalassemia minor (Thalassemia trait). He or she is healthy and leads a normal life. Most people with Thalassemia minor do not know that they have it. However, the affected persons can pass on the abnormal gene to their children.

Thalassemia major is a severe form of anemia. The affected person has inherited two Thalassemia genes, one from each parent. He or she may look normal at birth but within 1-2 years of life, will suffer from severe anemia, which leads to poor growth and development as well as a shorter lifespan.

The affected person will need blood transfusion every month to sustain life. At present, a bone marrow transplant is the only hope of a possible sure for Thalassemia major.

HOW IS THALASSEMIA INHERITED ?

(l) If only one parent has Thalassemia minor, the following can occur:

•  50% chance of having a child with Thalassemia minor
•  50% chance of having a normal child
•  none of the couple's children will get Thalassemia major.

(l) If both parents have Thalassemia minor, the following can occur:

•  25% chance of having a child with Thalassemia major
•  50% chance of having a child with Thalassemia minor
•  25% chance of having a normal child.

The chances are the same with each pregnancy, no matter how many children the couple may have.

WHO SHOULD GO FOR THALASSEMIA SCREENING ?

Since Thalassemia can be passed on from one generation to another, you and your partner should go for Thalassemia screening if you are:

•  planning to get married
•  starting a family

Thalassemia screening involves a simple blood test and is available at all polyclinics.

WHAT SHOULD I DO IF I HAVE THALASSEMIA MINOR ?

If you or your partner has Thalassemia minor, both of you should see a doctor for genetic counselling before you plan to get married or have a child. The doctor will explain the risks and discuss the choices you have. He may refer you to the National Thalassaemia Registry for further counselling.

The National Thalassemia Registry provides genetic counselling for people with Thalassemia and screening for their families. The staff at the Registry will be able to answer your questions about this blood disorder.

National Thalassaemia Registry

Level 6 Children's Hospital

100 Bukit Timah Road 

Singapore 229899

Tel: 6394 1863 or 6394  Fax: 6394 1867

Email: Nat.Thal.Reg@kkh.com.sg

WHAT IF I AM ALREADY PREGNANT ?

If you are already pregnant and both you and your husband have Thalassemia minor, you should go for a prenatal diagnostic test to find out whether your unborn baby has Thalassemia major.

Prenatal diagnosis can be done by chorionic villus sampling or by foetal blood sampling. Both tests are conducted under ultrasound guidance.

Chorionic villus sampling involves obtaining some cells from the placenta for testing. This is done during the 10th-12th week of pregnancy.

Foetal blood sampling involves obtaining a small amount of foetal blood from the umbilical cord for testing. This procedure is done at about 12-19 weeks of pregnancy.

Based on the result of the test, the doctor will advise you and your husband accordingly.

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Anemia refers to a disease in the level of hemoglobin below the lower limit of the normal range appropriate for an individual age and sex. Hemoglobin is an iron containing protein which combines reversibly with oxygen and subserves the key function of red cells in the carriage of oxygen from lungs to the tissue. It also gives the red blood cells their red colour.

WHAT ARE THE SYMPTOMS AND SIGNS OF ANEMIA ?

The symptoms vary with severity of anemia. The common presentations include lethargy, shortness of breath, palpitations, giddiness and pale appearance.

WHAT ARE THE COMMON CAUSE OF ANEMIA ?

This can be broadly classified into:

1) Blood loss: eg: Bleeding from peptic ulcers, hemorrhoids(piles), colon cancer, excessive bleeding during menstruaction.

2) Impaired red cell production:

(a) Nutritional deficiency (eg: iron, folate, vitamin B12

(b) Marrow infiltration by leukemia or advanced cancers.

(c) Ineffective red cell formation due to some congential or acquired disease.

3) Increased red cell destruction due to some congential or acquired disease.

WHO ARE THOSE AT RISK OF ANEMIA ?

These include:

• Vegetarians or anyone with inadequate diet
• Malabsorption problems
• Those who had operation for stomach or small intestines
• Pregnancy
• Women with heavy menses
• Alcoholism
• Kidney disease
• Cancer patients

WHAT SHOULD YOU DO IF YOU HAVE SYMPTOMS OF ANEMIA ?

To consult a doctor who may ask for a blood test.

HOW IS ANEMIA TREATED ?

The treatment will usually depend on the underlying cause of anemia. Blood transfusion may be required in certain situations, and can sometimes be life-saving in a severely anemia patients.

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UNDERSTANDING BLOOD TRANSFUSIONS

This information aims to help patients understand the blood transfusion process and its possible risks.

KEEPING OUR BLOOD SUPPLY AS SAFE AS POSSIBLE FOR OUR PATIENTS

In Singapore, blood donors come forward to support a life-saving cause without receiving any payment.

SCREENED …

Studies worldwide have shown that voluntary blood donors from low-risk populations are the foundation of a donors are also carefully screened using a comprehensive health assessment questionnaire.

… AND TESTED

Every unit of donated blood is managed under a comprehensive quality system benchmarked against stringent internationally recognized standards.

All blood units are tested for Hepatitis B, Hepatitis C, HIV, and Syphilis, using the most sensitive methods available.

The ABO group (blood type) and Rhesus type (positive or negative) are tested and confirmed on every unit to ensure that the donated blood is given to a patient with a compatible blood type. An antibody screen is also performed on every unit of donated blood, to check for high levels of significant abnormal antibodies in a donor’s blood which may result in adverse reactions during blood transfusion.

The decision on which patients require a transfusion and the transfusion amount is ultimately a clinical one made by your doctor. Doctors will carefully weigh the benefits of blood transfusion. Nationally, published clinical guidelines are in place to guide clinicians in the prescribing of the blood transfusions and these are based on international practice.

THE BLOOD TRANSFUSION PROCESS

The below guide shows what you can expect before and during blood transfusion.

1) A blood sample will be taken to confirm your blood group and to screen for unusual protein. This unusual protein may react against certain red cells in the blood you will receive during the transfusion. More blood samples may be needed to identify this protein if the screening is positive. You may therefore have to wait for some time for these tests to be completed, but they are necessary to ensure your safety.

2) Before the red cell transfusion is carried out, the donor’s blood is tested (called  cross-matching) against your own blood sample to ensure that the red cells to be transfused are compatible with your blood.

3) Before the transfusion starts, your identity will be carefully checked against the identity written on the unit of blood assigned.

4) That is why the nurse or doctor will ask you to state your name and identification details when talking a blood sample and prior to transfusion.

5) A blood transfusion is usually given through a small tube inserted directly into a blood vessel in the arm.

6) On average, it takes about two to three hours for each unit of red cells to be transfused, and about 20-30 minutes for each unit of platelets or plasma.

7) Because of the risk of bacterial infection or deterioration of the blood components when they are exposed to room temperatures, transfusion of each unit should not take more than four hours.

8) A nurse will monitor your temperature, pulse and blood pressure before the start of the transfusion, and will continue to monitor this several times during the transfusion.

9) If you feel unwell or become uncomfortable during or just after the transfusion, please notify the nurse immediately.

IS BLOOD TRANSFUSION THE ONLY OPTION ?

Not all patients have to undergo a blood transfusion for their conditions. Most people cope well with mild to moderate amounts of blood loss, or with mild anemia. When the blood loss, or with mild anemia. When the blood loss is mild, the body is usually able to regenerate new red blood cells and iron supplements can be given to aid this recovery.

Selected patients going for elective surgery may be suitable for autologous blood donation – a form of blood donation where a patients can pre-store his or her own blood for a short time, to be used during surgery.

Please discuss and queries or concerns you may have about blood transfusion with your doctor.

BLOOD TRANSFUSION RISKS

However, in spite of the stringent measures in place, there is still a very small percentage of risk of possible complications from blood transfusion.

TRANSFUSION – TRANSMITTED INFECTIONS

These could be due to:

Infectious Window Period: In the early stages of infections such as HIV, Hepatitis B and Hepatitis C, there is a window period when the blood is infectious, but the level of virus is too low to be detected by available laboratory tests.

Availability and Sensitivity of Tests:

Screening tests for some infections such a s malaria, variant Creutzfeld Jakob Disease (vCJD) and dengue are currently either unavailable or are not sensitive enough for detection.

New and Unknown Infectious Agents:

These are not detected due to unavailability of tests.

The current risks of contracting major infections through a blood transfusion in developed countries have steadily decreased over the years and now very low. The current estimated residual risks in Singapore is one per 110,000 donations for Hepatitis B, one per 1.3 million  donations for Hepatitis C and one per 1.1 million donations for HIV.

REACTIONS TO BLOOD TRANSFUSIONS AND OTHER COMPLICATIONS

There are patients who may occasionally experience mild reactions of serious complications after undergoing blood transfusions. These may appear during the transfusion or for certain reactions, within six hours after completion of the transfusion.

MILD REACTIONS

Mild reactions usually subside quickly after the transfusion is stopped and can be easily treated with medication. Most reactions that occur are mild in nature. Some examples of mild transfusion reactions are rashes or hives (about 1 to 3% of transfusions) and fever (about 0.1 to 1% of transfusions).

SERIOUS COMPLICATIONS

Serious complications are very rate but may include the following:

Excessive Fluid in the body and lungs which leads to shortness of breath (less than 1% of transfusions). Patients with heart or kidney problems may be at greater risks.

Transfusion Related Acute Lung Injury (TRALI) leading to difficulty in breathing (less than 0.02% of transfusions).

Severe life threatening complications arising from transfusion of blood group-incompatible blood products (less than 0.02% of blood transfusions).

Severe allergic reaction which may be life threatening (less than 0.005% of blood transfusions).

Bacterial infections (less than 0.002% of transfusions) which may be life-threatening and may be unavoidable despite all stringent precautions taken.

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Starting Desferal Infusion  

LIST OF ITEMS/EQUIPMENT NEEDED FOR DESFERAL INFUSION 

•  4 Pcs x Alcohol Swabs

• 1 Set x 20ml Crono Syringe

• 1 Tube x Water for Injection

• 1 Roll x Microphone Surgical Tape

• 1 Set x Scalp Vein Set (Butterfly Needle)

• 4 Vials x Desferrioxamine M 500mg Injection

• 1 Set x Desferal Infusion Pump with Battery Inserted

1] Wash Your Hand Clean.

2] Prepare a clean working area.

3] Gather all the items and equipment needed for the infusion.

4] When you are really, you can start by removing the top cap of all bottle of Desferoxamine.

5] Tear out a piece of alcohol swab and wipe the area where the cap were removed clean, top surface of the bottle itself.

6] Next open up your syringe from its package. If it's tear open, you might want to consider changing a new one to ensure it's clean and safe for use. Follow by opening the needle's packaging for the syringe.

7] After doing that plug the syringe needle onto the syringe itself and go ahead and remove the needle's cap.

8] Next withdraw certain amount of water from the water for injection plastic bottle that I am using (The amount of water is based/depended on yourself, the amount you usually used.

9] Then poke and insert the amount of water withdraw onto the Desferoxamine bottle.

10] Shake the bottle well for couple of seconds. (For example: 5-10 seconds)

11] Now you can withdraw the back from the bottle and level up by pressing the plunger rod (Which appear at the end of the syringe) a little till the liquid reach its/the top of the syringe.

12] Next cover the needle's cap back onto the needle itself. Then unscrew the needle's by turning the Luer-lock cap to the left and here you go the needle with it's cap is removed.

13] Now opened up your butterfly needle or whichever needle you're using from it's packaging.

14] Hold the end of the butterfly needle for my case which is a rubber material and plug/connect it into the syringe you had just prepared.

15] Push the plunger Rod a little to make sure the liquid is flowing through the butterfly needle. (For these older kind/version of the desferal injection pump the plunger Rod do not need/have to be removed from the syringe.

16] Now you're almost done. Put in the battery onto your desferal injection pump and have everything adjust and setup.

17] Place the syringe with the butterfly needle on the top of the desferal injection pump (For the newer small pump you just have/need to turn the syringe a little to lock it) (For the older model/version of pump make sure the syringe is tied and fasten and ensure it will not drop off)

18] Now clean the surrounding area you're going to inject the needle on your skin, remove the cap of the butterfly needle.

19] Grab a little of your skin and slowly push the butterfly needle into your skin.

20] After that tape the area up with these tape you're using, for my case I am using these roll injection white tape.

21] Press the start/on button on your desferal pump to began the therapy session.

22] Lastly place the desferal injection pump on the fabric holder with elastic belt or whichever kind you are using, and you're done with it.

SYRINGE PREPARATION FOR CRONO AMBULATORY SYRINGE PUMP

1. Put the supplied needle on the syringe with a clockwise rotation.

2. Fill up the syringe, aspirating the drug slowly to avoid disconnection between the rubber plunger and plunger rod. Verify the drug inside does not exceed 10 or 20 ml capacity.

3. Unscrew the plunger with a brisk counter-clockwise rotation.

4. Put the subcutaneous tubing on the syringe with a clockwise rotation.

5. Insert the syringe into the instrument with 90° rotation, making sure to detect a "click" which indicates the syringes is locked into the pump.

An Important Message to Blood Donors 

Donating blood is an act of great human kindness.

Your blood can save the life of another person.

As a blood donor, you want to make sure that you are giving good, healthy blood.

But there are times when your blood may not be suitable for donation.

Often you may feel quite well even through your blood may be carrying certain viruses or other infectious agents. But your blood may transmit these infections to people who receive it and harm them.

Before you give blood, you will be asked a number of personal questions regarding your health, travel and sexual history. This is necessary to ensure that you are well enough to donate and that you are not at risk of having an infectious disease which may harm the recipient of your blood donation.

The Blood bank, relies on you to tell them that is is safe to use your blood for transfusion and that the information given at your donation interview is true.

Conditions That Make Your Blood Unsuitable For Donation

1. Acquired Immune Deficiency

What is AIDS and HIV infection?

HIV infection is caused by the Human Immunodeficiency Virus (HIV l & ll). The end stage of this disease is called AIDS. HIV infection is mostly spread through.

• Sexual contact with an infected person
• Sharing contaminated needles  like those used by intravenous drug abusers
• Transfusion of contaminated blood (rarely)
• A HIV-infected mother to her unborn baby

Persons with AIDS have reduced resistance against infection because their body's resistance mechanism is significantly weakened. Hence, they may develop severe and fatal infections like pneumonia and rare forms of cancer.

BONE MARROW TRANSPLANT

What is bone marrow ?

The bone marrow is found in the spongy tissue inside bones. It produces red blood cells which fight infection and platelets which help blood clot. The body needs healthy bone marrow to fight infection and prevent bleeding.

What is bone marrow transplant ?

A bone marrow transplant replaces diseased or destroyed marrow in a patient with bone marrow failure with healthy cells from a donor. The replacement marrow travels through the blood stream to the bones where it begins producing normal blood cells.

Who needs a bone marrow transplant ?

Some patients have bone marrow which fails to fulfill its functions due to genetic illnesses or acquired damage from aging, viruses or environmental factors (e.g. chemicals, radiation etc). Others require high doses of Chemotherapy or radiotherapy for various cancers which destroy the bone marrow. These patients need a bone marrow transplant to give them a chance to restore their ability to fight infection and prevent bleeding. Donor bone marrow cells have the added advantage of being sometime able to attack the cancer cells. The Singapore General Hospital performs the majority of Bone Marrow Transplants in Singapore and is the National and Regional referral center for stem cell transplants. Many patients in Singapore and around the world have been saved in this way.

What are the types of bone marrow transplants ?

Autologous transplants involve storing the patient's own bone marrow and returning it after the bone marrow is destroyed as a result of cancer therapy. The obvious disadvantage is that the stored marrow may be contaminated with cancer cells which are then returned to the patient. 

In a syngentic transplant, an identical twin provides the marrow. In a allogenetic transplant, marrow is donated by another person, often a brother or sister whose own cells closely match the patient's in genetic makeup if this is not available, marrow from an unrelated donor who is closely matched in genetic makeup may be used. This is tested by the human leukocyte antogen (HLA) typing test.

What does bone marrow donation involve ?

Bone marrow donation involves harvesting bone marrow from the pelvic bone of donors. This is usually done under general anesthesia and there is only some mild ache at the site of harvesting for a few which is easily settled with mild painkillers. An alternative is peripheral blood stem cell donation which involves injection of blood growth factors and collection of stem cells from the circulating blood. For both procedures, donors can go back to full activity within a few weeks.

Who can donate bone marrow ?

Anyone who is fit to give blood can donate bone marrow. If the bone marrow donation is under general or epidural anesthesia, then donors should be for to undergo the respective anesthesia.

How can I help ?

If you are between the ages of 17 to 50, over 51 kg in weight, in good health and fully comprehend the implications of marrow donation, you may register yourself as a potential marrow donor by calling the WHO Immunology Centre at 6874 5049 / 6874 3318. A blood test will be done to determine your HLA type.

If you wish to donate to the Bone Marrow Program which finances the HLA-typing of potential donors, you may call 6738 7311 to make enquiries.

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WHAT ARE ABNORMAL BLEEDING ?

Platelets, coagulation factors and healthy blood vessels are required for normal blood clotting to prevent excessive bleeding.

What are abnormal bleeding symptoms ?

•  Recurrent and persistent bruising and appearance of "red spots" (petchiae rash) on skin
•  Passing out of black, gluey stool
•  Non traumatic joint swelling
•  Excessive and recurrent gum bleeding and "blood shot" eye

What causes abnormal bleeding ?

1) Abnormal blood vessels eg.

•  Vitamin C deficiency - Inherited conditions with poor collagen weak blood vessel walls

2) Reduced platelets numbers or function. These are mostly caused by

•  Viral infections eg. dengue fever
•  Autoimmune disorders eg. Systemic Lupus Erythematosis
•  Bone marrow disorders eg. marrow aplasia
•  Other medical conditions eg. liver disease and a small percentage is attributed by hereditary disorders.

3) Hereditary coagulation factors deficiency. The one more generally known is Hemophilia.

4) Acquired coagulation factors defect associated with other illnesses. Abnormal bleeding can be a symptom of various underlying diseases. Therefore, specific treatment will be directed at the underlying cause.

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WHAT IS LEUKEMIA ?

Leukemia is a cancer of the bone marrow and other blood forming organs. It involves the multiplication of immature white cells at the expense of blood elements.

What are the causes of leukemia ?

As for most other cancers, the majority of the leukemia is of unknown cause. However, certain conditions are known to cause leukemia; these include exposure to radiation, chemicals, inherited conditions such as Down syndrome etc. 

What are the symptoms of leukemia ?

The symptoms can be vague and non-specific. However, most patients present with the one of the following symptoms. Fatigue, breathlessness on exertion, bleeding nose or gum, easy bruising of skin, fever, weight loss, poor appetite etc.

What are the different types of leukemia ?

There are many types of leukemia. In general, it can be classified into acute and chronic and these can further subclassified into various types according to the cell of origin and their appearances.

Is leukemia an inheritable disease ?

There is little evidence for genetic factors. Although there are many reports if leukemia in the same family, their significance is unknown.

How is leukemia diagnosed ?

This usually requires several blood tests and a bone marrow biopsy.

How is leukemia treated ?

Leukemia is usually treated with chemotherapy (chemicals which have anti-cancer effects) The treatment course varies with different types of leukemia and also the age of the patients. In selected groups of patients and disease type, bone marrow transplant can improve cure rate.

Can leukemia be cured ?

In the past, leukemia was amoung the most difficult of cancers to cure. However, methods of treatment have greatly improved over past 10 to 20 years and more patients with leukemia, especially the younger age group, have been cured if this disease.

     Information above are provided by Singapore General Hospital - Haematology Centre

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BOOKS ON THALASSAEMIA

THALASSAEMIA ~ The Biography Book

Author: Sir David Weatherall

Description

Thalassaemia is the most common type of genetic disorder in the human population, and one of the first whose genetic basis was established.

Written by Sir David Weatherall, an expert in molecular medicine and the founder of the Institute of Molecular Medicine in Oxford in 1989, this tells the story of early reports of the disease, possible historical accounts, the identification of the disease as having an inherited basis, early work on thalassaemia as a disorder of the synthesis of haemoglobin, and from the 1960s, with the rise of molecular biology, the study of the condition at the DNA level.

The commonality of the disease raised an important evolutionary question: if thalassaemia is a genetic disorder then why hasn't it been selected out? Why does it persist, especially in Mediterranean populations? The great geneticist JBS Haldane suggested a reason - that carriers might be more resistant to malaria. Now that we have much more detailed understanding of the molecular basis of this set of diseases, has Haldane proved to be right? Weatherall shows that Haldane turns out to have been partially right. The book ends with recent improvements in treatment that have transformed patients' lives and a general assessment of how molecular approaches are impacting on medicine.

Thalassaemia: the biography is part of the Oxford series, Biographies of Disease, edited by William and Helen Bynum. In each individual volume an expert historian of medicine tells the story of a particular disease or condition throughout history - not only in terms of growing medical understanding of its nature and cure, but also shifting social and cultural attitudes, and changes in the meaning of the name of the disease itself.

Features

• The first exploration of the history of the disease, written by a world authority in the area
• Explores the story and background to the disease and the development of research into its genetic implications
• Fascinating account of the growing scientific understanding and changing attitudes towards the most common genetic disorder
• Examines the improvements in the control and management of the disease, and new treatments

Contents

Prologue

1) The First Desciptions of Thalassaemia

2) Thalassaemia as a Genetic Disease

3) Thalassaemia as a Genetic Disorder of Haemoglobin Production

4) The Diversity and Pathology of the Thalassaemias

5) Early Improvements in the Management of Children with Thalassaemia

6) Thalassaemia and the Dawn of Molecular Medicine

7) The Control and Management of Thalassaemia in the Cellular and Molecular Era

8) The Commonest Genetic Diseases: Was Haldane Right?

9) Epilogue: Thalassaemia and Molecular Medicine

Glossary

Bibliography and Further Reading

General Index

List of Illustrations

1) Lady Mountbatten with Jaspir Thapa, February 1960. Courtesy of Lady Brabourne

2) Letter from Lord Mountbatten to the author, May 1979

3) Thomas B. Cooley. Courtesy of Wolf Zeulzer

4) A child with severe thalassaemia. Courtesy of Elizabeth Letsky

5) A skull X-ray from a child withsevere thalassaemia

6) Peripheral blood film of a child with thalassaemia

7) Haemologlobin electrophoresis on starch gel

8) The haemoglobin patterns in the sickle-cell trait and sickle-cell B-thalassaemia

9) Haemoglobin changes in the sickle-cell trait

10) Ragged inclusion bodies in the red-cell precursors in the bone marrow of a patient with B thalassaemia

11) Globin synthesis in normal and B thalassaemic red cells

12) The effects of the development of prenatal diagnosis on the expected number of births with thalassaemia 

13) The genetic control and mechanisms of haemoglobin synthesis

14) The demonstration of a complete deletion of the a globin genes in babies with the Hb Bart's hydrops syndrome

15) The principles of restriction-enzyme mapping

16) Chorionic villus sampling

17) The world distribution of B thalassaemia and the common mutations in each region

18) The world distribution of the a thalassaemias 

Note: I have brought this book, recommend to all who will like to learn more about Thalassemia/Thalassaemia

No intention of copyright - All content above are from Oxford University Press - Their links below