Real causes of fatigue in thalassemia

So, we may safely assume that thalassemia sufferers are fatigued due to thalassemia.
But what would be the cause of that fatigue?

By finding what the causes are, we could convince doctors, researchers and other people
once and for all that this fatigue is real.

Of course in case of thalassemia major and intermedia the situation is a bit different – there is
additonal iron overload, ROS production etc. These mechanisms do not apply to thalassemia

Image result for Real causes of fatigue in thalassemia

As far as I can figure out:
1. Vitamin depletion.
Because of continuous production of erythrocytes different vitamins get used up faster than in “normal” people. Consecutive deficiency causes fatigue as different parts of body do not work
as they should and get fatiqued.
Vitamin deficiency can be easily alleviated by taking supplements (especially vitamins B complex)

2. Underoxygenation of tissues.
With unsufficient oxygen supply tissues do not have energy and experience different other problems, for example acidification.
But in case of sufficient hemoglobin (mine is 15,3 g/dl) underoxygenation should not be a problem, or is it?

Obvious solution to this problem is bringing hemoglobin to normal level (which may not be easy), taking antioxidants (they stop erythrocyte breakdown so they help increase hemoglobin) and taking vitamin E which makes blood thinner and erytrhocytes more flexible allowing better penetration of tissues.
Acidification may be fought by eating fruit or taking baking soda/sodium citrate.

3. Provoking inflammation/releasing different substances signalling brain that fatigue should be felt.
It is feasible that after erythrocytes break down there are certain substances released that cause inflammation (cytokines). Also the intracellular machinery may be somehow detected and this signals the brain to stop activity by inducing fatigue (strain -> broken cells -> necessity to stop the strain).
For example muscle cells release additionally endorphines, which cause this pleasant feeling of relaxation but also make you tired and a little dizzy.

Anyone has any idea of specific substance that can be released by erythrocytes breaking down?

4. Other disorders caused by thalassemia minor like allergies.
Well, as a matter of fact I think thalassemia’s involvement in causing other disorders is highly overrated but I mention it for the sake of the accuracy (I read such a statement in one of the threads). However my personal opinion is that simply all people get sicker due to pollution etc.

5. Bone pain.
Bone pain caused by bone marrow overproduction.

6. Heme/hemoglobin conundrum…
The first four items are kind of well recognized, this one is purely speculative.

This is the kind of question that can be answered probably only by a doctor/geneticist. If you are one or have a contact with one, you might want to pursue this question.

So I was wondering…

In case of beta-thalassemia (or alpha-thalassemia) one of hemoglobin chains is damaged.
Is it possible that this hemoglobin chain is used in different locations within the body?
Damaged hemoglobin in different locations would lead to impaired function and that would lead to fatigue (and other problems).

Possible different locations of hemoglobin:
– myoglobin in muscles
– complex III in electron transport chain
– complex IV (cytochrome c oxidase) in electron transport chain
– cytochrome c in electron transport chain

The question is if any parts of these compounds are expressed by the same genes as a particular hemoglobin? If so, we may have the answer.

This all gets even more complicated because of heme which is encoded by a different gene.
If it is the heme that is a common part of the above compounds, one would rather have porphyria and not thalassemia.

All in all this is all quite complicated (and I am not describing this correctly, I know) and a person is needed that knows exactly which part of the given compound is coded by a particular gene.

Why this kind of idea?
I have beta-thalassemia minor but I also have (metabolic) myopathy.
This means erythrocytes break down but also muscle cells break down. This is weird – it is much more likely that these two are interconnected somehow than they are not. So it is likely that the cause is the same for both of these disorders. So I am looking for this connection but I can’t find any.

This kind of connection in general might cause fatigue.



Pre-marriage Thalassemia test likely to be declared mandatory in Punjab

Pre-marriage Thalassemia test likely to be declared mandatory in Punjab

MULTAN: The Punjab government is considering to make Thalassemia Test mandatory before marriage mainly with to aim to check incidence of this serious life threatening disease, official sources of Health department disclosed on Tuesday.

The Provincial Health department has prepared a draft bill laying condition of Thalassemia test for couples before they get married, said the sources, adding that it has been sent to Law department for fulfilling legal formalities. Thalassemia is a blood disorder passed down genetically in which the body makes an abnormal form of hemoglobin in red blood cells that carry oxygen. The disorder leads to destruction of large number of red blood cells which leads to anemia.

The health department sources informed that after getting go ahead from provincial cabinet and standing committee, the bill would be tabled in the Punjab Assembly for approval. Punjab government is also mulling to issue a certificate to couples after the test, added the sources.

Acclaimed gynecologist and Principal Bakhtawar Amin Medical and Dental College, Dr Samee Akhtar said that the test should be made compulsory, especially in cousin marriage cases.He added that it is a simple blood test which tells whether next generation could have the disease due to defective genes of parents.

About its kinds, Dr Samee said that Thalassemia had two types including Thalassemia major and Thalessemia trait. If one gene of both boy and girl who are going to marry were defective, their babies would suffer from Thalassemia, he informed.

The gynecologist said that with the test recommended by medical science, the disease could be prevented easily. He regretted that most of our general public was uneducated and did not follow the suggested parametres even though they were sensitized about it. Dr Akhtrar hailed the step of Punjab government to check incidence thalassemia which kills people in early ages



Early bone marrow surgery is best for children with thalassemia: doctors

After a fourteen-month-old child with thalassemia underwent a bone-marrow transplant at an Andheri hospital, doctors said children should opt for a transplant as early as possible to avoid complications caused by repeated blood transfusions.

A doctor at Lokmanya Tilak Municipal General Hospital, Sion, which has a one-bed paediatric bone-marrow transplant centre said that last year seven bone-marrow transplants were performed on children with thalassemia, all of whom were more than two years old. Doctors said fourteen-month-old Prachi Bhanushali from Daman who was operated at Kokilaben Dhirubhai Ambani Hospital is one of the youngest to undergo the transplant.

“For children with thalassemia ,the earlier we do a bone-marrow transplant, the better it is in the long run. Such children require repeated blood transfusions until a transplant can be done,” said Dr Mamta Manglani, head of department, paediatrics, Sion Hospital.

Thalassemia is an inherited blood disorder, in which the body produces an abnormal form of haemoglobin, which affects oxygen supply to the tissues. Doctors said that for a child to have this disease, both parents must be carriers.

The condition is treated with blood transfusions, which can lead to health complications. “Repeated blood transfusions lead to iron buildup in the heart, liver and brain. This could lead to the early onset of diabetes and heart diseases,” said Manglani.

“Most patients undergo transfusions as the cost of a transplant is high. However, the excessive iron buildup caused by repeated transfusions is toxic,” said Dr Shantanu Sen, paediatric consultant and oncologist at Kokilaben Dhirubhai Ambani Hospital, who performed the transplant.

Prachi had high fever when she was just six months old. A blood test revealed her condition and doctors said she must undergo blood transfusions every two weeks.

“Her haemoglobin level was much lower than it should have been. My wife and I realised that both of us were carriers of the disease,” said Girish, 36, Prachi’s father who works at a ration shop in Daman.

A bone-marrow transplant is the only cure for thalassemia. “While a transplant is expensive, its cost equals that of ten years of blood transfusion,” said Vinay Shetty, founder of the non-governmental organisation, Think Foundation. Prachi’s surgery cost approximately 12 lakh, most of which was funded by charity groups

Doctors said that in most cases, siblings turn out to be a match. In Prachi’s case, her mother was a bone-marrow match, and could become the donor. “During the Human Leukocyte Antigen (HLA) testing to determine compatibility between the donor and the recipient, we found that Prachi’s mother, Chandrika, was the perfect match,” said Sen.

Experts said the high rate of intra-caste marriages in India is why parents turn out to be perfect matches for their children. “It is very rare to for the mother to be a match. We extracted stem cells from her mother’s bone marrow and successfully transplanted them into Prachi. She will be discharged today,” Sen added.

“Outside India, parents are rarely suitable matches for bone-marrow transplants. However, in India, about 3% of the donors are parents,” said a doctor from KEM Hospital, Parel.

Health experts said Prachi belongs to a community in which the prevalence of thalassemia is high. “People belonging to such communities should get themselves screened before planning for pregnancies,” he added.

What is Thalassemia?

Thalassemia is a blood disorder in which the body makes an abnormal form of haemoglobin.

If both parents are carriers of the disease, there is a 25% chance of the child getting it.

While blood transfusions help, doctors say a bone-marrow transplant is the only long-term solution.

One in every 25 Indians is a carrier of thalassemia, according to studies

The prevalence of thalassemia is high among communities such as Sindhis, Gujaratis, Punjabis, Mahars and Kutchis



Ripples on the Water (Beta Thalassemia)

Eight years ago I saw my daughter for the first time… a sad face standing behind metal bars.

She looked scared and confused, with an expression that seemed more like an old woman than a young child. I searched her eyes and saw… nothing. No life, no twinkle, no joy.

Expecting a referral for months, I had read countless blogs of others who had gone before us. I had seen children on the day they left their orphanages and how they changed with the love of a family. I knew that the pain of being orphaned was real, but nothing prepared me for seeing her expression. All the books we read and all the studying we had done had educated us on the effects of institutionalism – how it alters the brain and wreaks havoc on the soul. There, in her eyes, I saw it. I understood. She was lost, utterly alone, and losing her sense of self by the moment. The bars in front of her seemed a metaphor for the child locked inside.


We read through her file and learned she had a rare blood disorder called beta thalassemia. She would require blood transfusions every several weeks to live, as well as chelating medicines. This was a huge thing for our family to consider. Could we do this? Should we do this? Would she live into adulthood? Statistics were saying hers was the first generation that might live an average lifespan in America… but no one knew for certain. She might not. Or perhaps she would obtain a disease from the transfusions themselves.

Fear entered my heart. Could I say goodbye to a child I had learned to love? I looked at her face and realized all over again that this adoption was not about me. It was about her. It was about a little girl halfway around the world that would most certainly die without treatment, but whose soul was already dying a slow painful death from invisibility. To me, her greatest and most immediate need was love.

Each time I thought of her, I remembered the verse from Isaiah where the Lord speaks and says, “I have called you by name. You are MINE.” We wanted this precious child to know that out of the whole world, we were picking her to be ours… to be His. And so we named her Mia, which means “mine.”

Mia came home in 2008 and our church family watched the tiniest pipsqueak of a girl begin to bloom. When she came home at almost three years old, she could barely walk and had no language. Her fears were huge (and some still are), but she loved being loved. She found her smile and her laugh and her love for pink and polish. She received medicine and food and a daddy who cherishes her.

Her transformation has been amazing and the effects continue to cause a ripple.


As people began to see Mia and other children welcomed home through foster care and adoption, fear began to vanish among those we knew. God began to do a work in our church as we learned that orphans aren’t statistics and that God is able to do more than all we can ask or imagine.

It’s so tempting to be discouraged by the enormity of injustice in the world. We cannot solve the orphan crisis through adoption; the roots run too deep. But for a little girl behind bars, it gave her the wings to fly


3d rendered illustration of many blood cells

Interesting Facts about Thalassemia Carriers

  1. Thalassemia is in fact a Greek word. The word “Thalassa” means sea and “Emia” means blood.
  • It is a genetic disorder inherited from either or both of your parents.
  • It is the commonest single gene disorder in the global population .
  • In Malaysia, it is estimated that 1 in 20 people is a thalassemia carrier.
  • The disorder primarily affects your red blood cells (RBC) resulting in reduced or absent production of haemoglobin –the oxygen carrying vehicle in your body resulting in a medical condition known as anaemia.

Source: blog.treatmentassistance.in

  1. Simple concepts about heredity that you need to know.
  • In every generation, genes are shuffled and re-shuffled. Half of your genetic make up comes from your father and the remaining half comes from your mother.
  • Eye color is an example of inherited characteristic, i.e. assuming that the roots of your family trees are “purely”Asian, that explained why you have “brown eyes” instead of blue eyes.
  • Similarly, this concept is applicable in thalassemia gene inheritance.
  • There is one important term that you need to be clear of to understand how thalassemia is inherited , i.e. ‘thalassemia carrier’.
  • A thalassemia carrier is a person who has a copy of the thalassemia gene.If you are a carrier, most of the time you will appear healthy and do not manifest the symptoms of thalassemia. However, a carrier can pass the abnormal gene to the future child (remember it was mentioned earlier, every individual carries one copy of gene from the mother and one from the father).
  • So now, find out what are the chances of your offspring inheriting the thalassemia gene by continue reading this article.


  1. “I am perfectly healthy and so was my family member…it seems to me ignorance is bliss”
  • Have you gone for thalassemia screening? If your answer is NO, perhaps you should visit the nearest clinic soon because your present decision might have a great impact on your future generation.
  • In a situation where there is one parent carrier ( assuming you are a carrier and your partner is a normal individual), the chances of having a normal child or a thalassemia carrier child is 50% respectively (Refer to Diagram).
  • The situation has become very much different if the couples are both carriers. There are 3 possibilities of your child’s genetic inheritance outcome; normal individual (25%), carrier (50%) or affected individual (25%) – also known as thalassemia major that will be blood transfusion dependent (Refer to Diagram).
  • When one parent is an affected individual (thalassemia major patient) and the partner is a carrier, all your offspring will carry a thalassemia gene. Thus, you will not have a normal invidual. Your child will either be a carrier (50%) or affected individual (50% – thalassemia major).
  • If both couples are thalassemia major individual, all of your offspring will be affected individual (100%)
HOW THALASSEMIA GENE IS INHERITED The following diagram shows the inheritace patterns of all types of thalassemia i.e alpha(α) or beta(β) globin chain gene defect

The following diagram shows the inheritace patterns of all types of thalassemia i.e alpha(α) or beta(β) globin chain gene defect

  1. What can you do to determine if you are a thalassemia carrier?
  • Thalassemia carrier is usually a healthy individual.He/she does not manifest sign and symptoms of thalassemia and therefore undetected most of the time.
  • Thalassemia CAN ONLY be detected and confirm by blood test.
  • For the initial screening, widely available in private and government clinics, a full blood count will be suffixed to rule out the risk of thalassemia carrier.However, haemoglobin analysis or DNA analysis will give you a confirmatory diagnosis of your thalassemia status.
  • One will only need to undergo thalassemia screening once in your lifetime as your status will not change overtime.
  • As discussed earlier, thalassemia is a genetic disorder (your child has a chance of inheriting thalassemia gene) and if you are a healthy carrier it might go undetected giving you a false sense of assurance of your status.


  1. Thalassemia patient- What they go through for the rest of their lives?
  • Thalassemia patient, most of the time, shows the disease manifestation few months after birth. The child is typically pale (anaemic) and have failure to thrive.
  • They are blood transfusion dependent for survival-MONTHLY basis and at times it maybe on weekly basis, depending on the individual.
  • Due to the frequent blood transfusions, they are at risk of iron overload that leads to vital organs damage such heart and liver failure.
  • Bone marrow transplantation is the only cure, but finding a suitable donor is challenging and very much depending on the medical expertise available.


  1. Success story from Iran Thalassemia Pre-marital Screening Program
  • The number of carriers detected has increased from 0 in 1000 to 4.1 in 1000 population2.
  • After 20 years of the compulsory premarital screening program, study found that the birth prevalence of beta thalassemia child reduced 30 % in Iran1.
  • The most important benefit of premarital screening is that it gives thalassemia carriers and carrier couples the possible range of informed choice and decide on their current or future pregnancy.
  • In our country, thalassemia screening program is not compulsory but you are encourage to go for screening.


  1. To summarise what you need to know about thalassemia
  • Thalassemia is preventable.
  • Screening is easily and widely available .
  • Thalassemia carriers are most of the time perfectly healthy individuals, BUT are capable of transferring the genes to their offspring.
  • Regular blood transfusions with other treatment (iron-chelation) ensure the survival of thalassemia patient.The only cure for thalassemia patient is bone marrow transplant.
  • Eventhought treatment is available, we believe that “Prevention Is Always Better Than Cure” and thalassemia is definitely a highly preventable condition.
  • source;http://www.mmgazette.com/

Carotid intima-media thickness and oxidative stress markers for assessment of atherosclerosis in children with b thalassemia major


The present study evaluates carotid intimamedia thickness (CIMT) in children with b thalassemia major to assess atherosclerosis and its relation to the underlying proposed causative mechanisms via lipid peroxidation product malondialdehyde (MDA), oxidized lowdensity lipoproteins (LDL), total antioxidant level, and lipid profile. A cross sectional study was conducted on 62 children (31 cases and 31 controls). CIMT by high resolution ultrasound and biochemical parameters i.e., total cholesterol, triglycerides, high-density lipoproteins, LDL, Oxidized LDL, lipoprotein (a), lipid peroxidation product MDA and total antioxidant were measured in enrolled subjects and compared. In our study, CIMT was significantly increased in b thalassemia major patients’ as compared to healthy controls. Mean CIMT in cases was 0.69±0.11 mm and in controls 0.51±0.07 mm. Mean oxidized LDL (EU/mL) in cases 39.3±34.4 (range 14.4 to 160) was significantly raised (P=0.02, t test) as compared to controls 23.9±13.4 (range 12 to 70). In our study we found MDA levels (nmol/mL) to be increased in b thalassemia patients as compared to controls. Mean MDA was 10.0±3.27 (4.41 to 17.48) in cases while in controls was 6.87±4.55 (1.5 to 17.9). Our study results show CIMT as an early marker of atherogenesis in b thalassemia major. Oxidative stress markers are also increased in b thalassemia major patients and lipoprotein (a) shows a positive correlation with CIMT. The present study points towards various atherogenetic mechanisms in b thalassemia major.recessive single gene disorder of hemoglobin chain synthesis. Every year approximately 100,000 children with thalassemia major are born world over, of which 10,000 are born in India.1 In b thalassemia, inadequate b globin chain production leads to decreased levels of normal adult hemoglobin (Hb A) and excessive production of α chains. This leads to precipitation of α chains, which leads to hemolysis and ineffective erythropoiesis. Ineffective erythropoiesis constitutes the main patho-physiology behind all signs, symptoms and complications of b-thalassemia.2 Clinically b thalassemia major patients have symptoms of severe progressive hemolytic anemia typically presenting around 2-6 months of age. Treatment of patients with b thalassemia major includes regular lifelong blood transfusions and iron chelation. Iron overload occurs universally in all b thalassemia major patients over the disease course and results in varied complications. Iron overload in these patients result from ongoing chronic hemolysis, repeated blood transfusions, ineffective erythropoiesis and increased iron absorption from gastrointestinal tract.3,4 Of the various complications, cardiovascular complications are the leading cause of morbidity and mortality in patients with b thalassemia major.5 Currently, cardiac complications contribute to cause 71% of deaths in patients with thalassemia major.6 Atherosclerosis is an important forerunner of cardiovascular complications. Atherosclero – sis in b thalassemia major patients may be the result of iron-overloaded state causing oxidative modification of lipids, altered lipid profile and vascular dysfunction. Studies have also shown relation between iron load and risk of atherosclerosis.7 Iron overload is associated with generation of oxygen-free radicals and peroxidative tissue injury.7 Oxidative modification of low-density lipoprotein (LDL) plays a central role in the sequence of events leading to atherogenesis-related vascular alterations. Malondialdehyde (MDA), a by-product of lipid peroxidation is found to be increased in patients with b thalassemia major.8 So, plasma MDA levels in b thalassemia patients represent a sensitive index of the oxidative status of LDL in vivo. 8 Many studies have shown alterations in blood lipid profile in thalassemia major and intermedia patients.9,10 Thalassemia patients also have altered endothelial relaxation, intimal thickening, abnormal vascular stiffening, and degeneration of elastic arteries.3 Continuous blood transfusions along with iron overload leading to endothelial dysfunction via peroxidative tissue injury has also found to be an important precursor of atherosclerosis in patients with b thalassemia.11 Carotid intima-media thickness (CIMT) is a non-invasive method to detect early subclinical atherosclerosis and it correlates well with overall vascular injury and extend and severity of coronary artery disease.7,12 There is upcoming role of CIMT for detection of early atherosclerosis in children with b thalassemia major.13 The present study evaluates CIMT in children with b thalassemia major to assess atherosclerosis and its relation to the underlying proposed causative mechanisms via lipid peroxidation product malondialdehyde (MDA), oxidized LDL, total antioxidant level, and lipid profile. There is no such study, to the best our knowledge, correlating CIMT with lipid peroxidation products and antioxidant levels.

if read full article source;http://www.pagepressjournals.org/index.php/thal/article/view/4939/5115