Thalassemia intermedia today: should patients regularly receive transfusions?

With the advancements in treatment for thalassemia, an important question is now being asked. Should the criteria for deciding when to transfuse in thalassemia intermedia be changed to reflect both advances in treatment and also the advancements in understanding the results of long term low hemoglobin levels in patients? With a better understanding of the consequences of low Hb in patients, we may be seeing a shift to transfusion/chelation regimens in intermedias to help avoid these complications and to improve overall quality of life in intermedias. For the parents of the non-transfusing intermedias, the question has to arise, why their children can't have the same quality of life being provided to thal majors who begin therapy very early in life. Perhaps instead of looking at how low an Hb can be maintained without transfusion, the goal should be to optimize the health of intermedias by maintaining an Hb high enough to enjoy life to its fullest, while also preventing many of the complications which are the result of low Hb. In the past, unsafe blood supplies have played a major role in the decision to not transfuse, along with the difficulty of chelation. With advancements in blood safety and with the age of oral chelation upon us, the previous thinking is now being re-examined. The benefits of providing adequate oxygen supplies to the body through a normal Hb are numerous, as are the consequences of not transfusing. While researching some related issues I have also come across recommendations that majors should also be kept at higher Hbs in order to prevent many complications such as pulmonary hypertension. The goals of transfusion therapy are constantly being re-thought and maintaining a close to normal Hb is becoming the goal. Strict compliance with chelation is absolutely necessary, but quality of life can be improved with adequate Hb levels.

http://www.ingentaconnect.com/content/bsc/trf/2007/00000047/00000005/art00009

Thalassemia intermedia today: should patients regularly receive transfusions?

Authors: Aessopos, Athanassios; Kati, Maria; Meletis, John

Source: Transfusion, Volume 47, Number 5, May 2007 , pp. 792-800(9)

Publisher: Blackwell Publishing


β-Thalassemia is an inherited hemoglobin disorder characterized by reduced synthesis of β-globin chain. The severity of clinical course distinguishes this heterogeneous disease in two main subtypes: thalassemia major (TM) and thalassemia intermedia (TI). TI has a later clinical onset with a milder anemia that does not require transfusions at least during the first few years of life. The clinical picture of TI patients who have not received transfusions or have occasionally received transfusions is dominated by the consequences of chronic hemolytic anemia, tissue hypoxia, and their compensatory reactions, such as bone deformities and fractures, extramedullary hemopoiesis, spleen and liver enlargement, hypercoagulability, and pulmonary hypertension. These complications, especially the latter two, are getting more frequent and severe over the years. Nowadays, although TI patients have almost no changes in the course of the disease, well-treated TM patients with regular transfusion-chelation therapy showed suppression of the anemia-related disorders in parallel to prolongation of life. The new oral iron chelators and the magnetic resonance imaging application for early detection of heart iron load are promising for further improvement on survival. CONCLUSIONS:

Considering the current cost-benefit balance of regular treatment in TM as well as the frequency and severity of complications in TI, it seems that the majority of TI patients will be benefited if this kind of treatment is applied targeting prevention and not palliation of the anemia-induced complications.

Document Type: Research article

DOI: 10.1111/j.1537-2995.2007.01192.x

This raises many questions about the future direction of treatment in intermedias and this trend will be watched closely. I must admit that when I read this article, I hear the voice of Shikha in my head urging parents to have their intermedia children transfused. Shikha has based this on what she has seen in her daughter and other patients who transfuse and how much the quality of their lives has been enhanced by transfusing. Shikha, the researchers are catching up.

Andy......

You are reading my mind!!!!!!!
I have been feeling for the last several months that Olivia should be on a regular transfusion schedule. I know all of he issues and chelation that come along with the txs, however , theses days when I look at Olivia and see that she is slowing down and she is so pale and sickly looking my heart breaks....I really feel my heart ache. At our last Drs appt., the Dr we saw was helping out and although he has many decades of experience... I felt like he was reading out of a text book... I feel with Olivia's form of thal intermedia, she would greatly benefit from regular transfusions... I feel we have done our best to keep her from being tx....She was 4 yrs old when she received her 1st one, and now it is time....Another thing that made me upset was that the Dr. was able to see a facial trait in Olivia... a flattening  of her face between her eyes...I know that my husband and I are good parents and all we want is for our children to be healthy and we will make certian that. I have a few questions...Should a thal intermedia's hb be kept as high as thal major's? If so how do we get it to that level?
Thanks Kathleen

Kathleen,

If you do decide to begin regular transfusions, please insist on genotype matching of blood in addition to phenotype matching as it can help prevent antibody reactions.

More and more I am becoming convinced that in the interest of proper development, low Hb intermedias should transfuse if they cannot raise their Hb with inducers. Looking down the road, it will also be important to have healthy patients to take best advantage of new therapies.

Hi everyone.....
Just wanted to let you know Livi has ans appointment tomorrow.....I spoke ith Dru from Dr Vichinsky's office and we have an appointment on 8/14.......I will keep you all posted...
Kathleen

More and more I am becoming convinced that in the interest of proper development, low Hb intermedias should transfuse if they cannot raise their Hb with inducers. Looking down the road, it will also be important to have healthy patients to take best advantage of new therapies.

when should a thal. inter. child be transfused? at which hb level?

The decision to transfuse should not be made based on Hb level alone. Traditionally, the range for transfusion for intermedias was when it dropped below 7-8, but physical development is also key. If development is close to normal, then a patient may be able to go without transfusions. If there is significant poor physical development, which can be measured by a doctor, then it is now widely accepted that the patient should start transfusions to ensure that normal development takes place. With modern chelation methods available to remove excess iron, transfusing intermedias is becoming more accepted. It may be possible for some patients to transfuse during the developmental years and reduce or eliminate transfusions once growth is completed. Patients who have borderline Hb levels should have other methods tried first, such as natural fetal hemoglobin inducers like wheatgrass or drugs like hydroxyurea or butyrate before making a decision to transfuse, as some patients are far more receptive than others to hemoglobin inducers.

The decision to transfuse should not be made based on Hb level alone. Traditionally, the range for transfusion for intermedias was when it dropped below 7-8, but physical development is also key. If development is close to normal, then a patient may be able to go without transfusions. If there is significant poor physical development, which can be measured by a doctor, then it is now widely accepted that the patient should start transfusions to ensure that normal development takes place. With modern chelation methods available to remove excess iron, transfusing intermedias is becoming more accepted. It may be possible for some patients to transfuse during the developmental years and reduce or eliminate transfusions once growth is completed. Patients who have borderline Hb levels should have other methods tried first, such as natural fetal hemoglobin inducers like wheatgrass or drugs like hydroxyurea or butyrate before making a decision to transfuse, as some patients are far more receptive than others to hemoglobin inducers.

thanks
another question
is there are any recommended doses regarding whetgrass and resveratrol?

Dosage for wheatgrass and resveratrol varies depending on the amount contained in each product. Resveratrol dosage for a child is usually no more than one capsule per day. Wheatgrass can be taken in larger doses and if he is taking tablets it can be 2-4 daily. If he is taking the supershots from wheatgrassactive, one per day is the dose.

Dosage for wheatgrass and resveratrol varies depending on the amount contained in each product. Resveratrol dosage for a child is usually no more than one capsule per day. Wheatgrass can be taken in larger doses and if he is taking tablets it can be 2-4 daily. If he is taking the supershots from wheatgrassactive, one per day is the dose.

thanks
thats mean as recommended or written on the bottle
i was thinking thal. pt. may need a higher dose

With wheatgrass, a higher dose may eventually be possible but use resveratrol only as recommended.

Hi Kathleen

I read your post's , have u ever considered using hydro oxy urea, my son has been using it for more than  6 years now. When these kids are little, they can still have a normal growth with an hb of 7 however they need higher hb when they reach 8 years of age, cos they are growing. I suggest you check all teh options before you resort to regular transfusions. We used an injection called recormon which was not very helpful in my son's case.

Also in my son's case we landed up giving one or two transfusion per year. We did not resolve to giving regular transfusion, cos in intermedia cases their bone marrows are working but not like normal people so if we go on a hypertransfusion drive there is a possibility that cos the body gets used to the regular transfusions so the functioning bone marrow also slows down.

Please consider transfusions but not hyper transfusions, this is from my personal experience. Monitor her growth charts carefully, and please do the liverfunction test kidney function test and bone density test yearly. this way if there is any anomalie it will be caught and transfusions are always there as a back up.

Hi Poo gill,

Olivia was on hydroyxurea for nearly 2 yrs and did ok her hb was between 7-8.6. She is having some changes in her forehead and some facial changes. I have visited Oakland and this is what we decided to do for 6mo. to see the difference between tx vs. non tx. So far i see a big difference for the better in Olivia. I will keep you posted on her progress.
Kathleen

Hi Kathleen


I was discussing Thal intermedia with Dr Ali of Lebanon. He was supporting Hydro oxy urea. So I was glad to see that I was on the right track with the drug. Is Olivia still taking hydro oxy urea.

My opinion is that you please continue hydro and give her the transfusions too but not hypertransfusions. The reason for this is,  as I have heard from other people that if we go in the hypertransfusion mode, the bone marrows of thal intermedia which does produce some RBC's unlike the thal major's gets used to getting blood from outside and then shuts down. There is a high chance of the child becoming dependent on transfusions. if she is 8.6 with hydrea then surely she will not need so many transfusions. Please discuss this with your doctor.  If her height weight and growht is as per normal growth percentile then dont push her for more transfusions. Intermedia is very complicated as per the doctors in the conference and is based a lot on clinical studies of individual child.

How old is Olivia?

hi poo gil....
Olivia was on hydroxyurea for 2 years she did ok and then her hb slowly declined. She was a 7.1 the first time she was tx. I went to oakland children hosp and saw dr vichinsky and he wanted her on tx for 6 mo and then off for 6mo to see if there would be a diffference. I dont think she is being hyper tx she is going every 4 week we will not let her get below a hb of a 10.  Also Olivia is having a moderate thickening of her forehead due to low hb. I really feel that Olivia will be tx the rest of her life or until a cure is found. I know that thal intermedia patients can live without tx but I want her to feel good and grow and develop normally with no deformities. She has  been so full of energy and eating so well. She gained a pound in 4 weeks and grew 1/4 of an inch. Olivia is 4 1/2 now.  I thank you for your post its important to hear others opinions and facts.....thanks again.....
Kathleen

It is good Kathleen that Olivia is doing well. I am really happy for you. Dr Vichinsky knows best. You are in good hands.

In fact Dr Vichinsky was mentioning abt some new drugs to Sharni for Intermedia, you might want to discuss with him directly. Also tell us about it too.

Take care