The heart in transfusion dependent homozygous thalassaemia today

I have posted the full text of this just released article under the Documents section at

http://www.thalassemiapatientsandfriends.com/index.php?topic=1451.msg11816#msg11816

I would highly recommend that every patient makes sure that their treatment centers and doctors are made aware of this most important review. The original article can be found at

http://www.blackwell-synergy.com/doi/full/10.1111/j.1600-0609.2007.01018.x?prevSearch=allfield%3A%28heart+in+transfusion+dependent+homozygous%29

I cannot overemphasize the importance of what is contained in this article. The number one killer of thals is heart failure and taking the essential steps to prevent this will greatly extend the lives of thals. The article states that over 80% of thals are now surviving past the age of 40, whereas during the 1960's 80% of patients died by age 16. This is remarkable progress made possible by iron chelators and for thals to continue this amazing improvement, proper monitoring and management is necessary. Being proactive and supplying your care giver with the most current information is an important way that thals can use to make sure they are getting optimal care. And most importantly, each patient must make the decision to comply with treatment and stick to that decision.

Many may find it surprising to see that 80% of thals are now living into their 40's. If this is not true where you live, make sure that every medical professional involved with thal that you know is made aware of this article. Following these guidelines will have a very positive effect on survival rates among thals.

Hi Andy,

Thanx for such a great article,i haven't read it completely yet,but questions i wanted to ask anyway were,zainab is taking ferriprox three times a day,it makes 1500 mg a day,according to the article the dose of defriprone should be 75-100mg/kg divided in three doses daily, zainab's weight is 26 kg,now if i calculate the lowest dose i.e 75 mg/kg,it makes 1950mg,should i increase her dose to 4 tabs a day?should i ask her doctor first?another thing is she is taking two tabs of folic acid dailu,5mg each,can i increase this dose also and make it 4 tabs daily,the main reason is zainab's hb used to be 10 on three weeks tranfusion duration,but since last few months it's always lower then 10,like in between 9 and 10,my husband is arguing with me that it has started happening since she started taking IP6,i don't think so,but he is insisting on quitting IP6 for a while to check it,but i don't want to,bcoz it has bring some colour on her cheeks back,after so long time i,ve seen her face pink,i don't know what to do,plz help me out.

ZAINI.

Hi Zaini,

Always ask your doctor before adjusting the dose of any medicine. Chelating drugs require specific monitoring, with L1 it is the white blood cell count. Your doctor always needs to know the exact dose she is taking. 

The most likely reason that Zainab's Hb level has dropped between transfusions is that she is growing and requires a higher blood volume. This is something all parents of thals should understand. The transfusion requirements of a child may change as they grow. Bigger bodies need more blood. This would be a gradual change and eventually she may need either more frequent transfusions or more blood per transfusion. It is also possible that it is a temporary change in Hb, as even changes of season have some effect on the measured Hb level.

Phytic acid (IP6) has been studied extensively, because it was feared that people who eat a lot of grains (whole grains are high in IP6) might suffer from anemia because of it. Tests on rats showed that there was no effect on hemoglobin levels and no effect on the normal absorption of iron.

http://jn.nutrition.org/cgi/reprint/90/4/423.pdf

The hemoglobin values in table 2 show
that, even at the submarginal level of 10
ppm of iron, the rate of hemoglobin re
generation was not affected by the pres
ence of either level of dietary phytate.
When expressed on the basis of milligrams
of iron consumed, there were no signifi
cant differences, at either level of iron,
between control values and those of the
diets containing phytate.
It was concluded from the results of this
work that high levels of phytate have no
effect on iron absorption in the rat. There
fore, the presence of phytic acid in foods
fed to rats should not be expected to de
crease the physiological availability of the
iron in such foods.

IP6 had no effect at all on the Hb level. What has been discovered is that IP6 works where it is needed in the body. It is found in every cell in the body and supplementing with IP6 has shown abilities to reduce the damage that iron does to cells, lower blood glucose levels in diabetics and inhibit the effect of iron in cancer cells. IP6 has also been shown to extend the lives of cells with its antioxidant properties.

One thing I have been seeing mentioned a lot is the supplement L-Carnitine, which is a precursor of nitric oxide, and has been shown to extend the life of red blood cells in thalassemics.

http://grande.nal.usda.gov/ibids/index.php?mode2=detail&origin=ibids_references&therow=800548

L-carnitine is an essential element of intermediary metabolism and also was shown to be effective in maintaining normal red blood cell (RBC) function. This study aimed at investigating plasma free L-carnitine concentrations and effectiveness of L-carnitine supplementation in protecting deterioration of RBC properties in beta-thalassemia major patients. Plasma free L-carnitine concentrations were determined in the blood samples obtained before their regular transfusion (about one month after the previous transfusion). Each patient received 100 mg/kg/day oral L-carnitine supplementation. RBC deformability, lipid peroxidation and intracellular free calcium concentrations were investigated before and after this treatment. Plasma free L-carnitine levels and RBC deformability before the treatment were found to be lower whereas lipid peroxidation and intracellular calcium concentration in RBC were higher compared to those of the control subjects before the L-carnitine treatment. After one month supplementation of L-carnitine lipid peroxidation and intracellular calcium concentrations were found to be decreased and RBC deformability was improved, accompanying the significantly increased plasma L-carnitine concentrations. These results suggest that L-carnitine can be used as a supplement in beta-thalassemic patients, to prevent RBC deterioration.

I have seen studies on L-carnitine many times and am surprised that it is not more widely recommended for thals.

Ask the Experts

Question: 

My child needs a bone marrow transplant , but there are no matched donors in the family. What can be done?

Answer: 
 There are experimental protocols offering transplant from alternative donors, which are higher risk than transplant from an HLA-matched sibling. The family needs to be fully aware that the risks of these alternative transplants include death, chronic graft vs host disease, graft rejection (go through all the procedure and end up still with sickle cell disease), and reproductive sterility. Usually the eligibility criteria are: stroke or silent brain infarct and chronic transfusion, recurrent acute chest syndrome (3 episodes) or recurrent hospitalizations for pain (3/yr) despite hydroxyurea and other interventions. Some protocols are only for children under 17yrs.

Different protocols have alternative donors such as HLA-matched unrelated cord blood, partially HLA-matched family member, or HLA-matched unrelated donor. Different preparative regimens are used to combine immunosuppression and bone marrow suppression. Medical compliance is essential and the family needs to set aside all other obligations to follow the pre-transplant evaluation and the post-transplant period can involve very intense medical care for 6 - 24 months... this is a level of intensity more similar to cancer care than to sickle cell care. The child will have to take multiple medications for several months, central line for medications and nutrition, and may have 3 clinic visits a week and frequent hospitalizations. Psychosocial stability and family support are extremely important -- this will be a challenge for a family from Savannah to get a transplant someplace else. However, if they are interested, the family should ask the child's hematologist about making a referral for consultation at a pediatric bone marrow transplant center Emory, Duke, and Jacksonville are relatively close to your patient in Savannah. The transplanters at St. Jude in Memphis, TN, and National Institutes of Health (Dr. John Tisdale) also have sickle cell transplant protocols and often conduct consultations for patients from far away.

Transplantation is the only sickle cell treatment offering the possibility of complete cure from sickle cell disease. However, there are real risks involved, and the alternative donor protocols have higher risks than the HLA-matched-sibling donor transplants. For a patient and family to take on these risks requires considerable discussion to make sure that they understand the risks and their responsibility for medical compliance.

Sincerely,
-Lewis Hsu, MD, PhD
Pediatric Hematologist

For more frequently asked questions please see:  http://www.scinfo.org/faq.htm


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This make interesting readings enjoy it
Kathy

Hi Kathy!

Thanks for sharing this.

There are always alternates besides the recommended treatment, but like the post said the protocols change and so does the risk factors.

It is always very very very hard to decide to opt for a specific treatment, weighing the risks involved against the success.

Thanx Andy,

For your generous reply,i never thought IP6 can play any role in zainub's low hb,and i guess you are right ,chnage in hb can be due to various factors,i understand this, but still not knowing the exact reason frustrates me,and there has been a lot of variation in her hb level since last few months,it was like
17/08/07 =10.6
13/09/07 =9.8
06/10/07 =9.7
27/10/07 =10.1
24/11/07 =8.6
15/12/07 =9.3
05/01/08 =9.6
26/01/08 =10.5

I want to keep her hb above 10,but i am unable to make a pattern due to the variation in her hb levels.
I will ask her doctor about the dose of ferriprox ,but what about folic acid,do i have to ask him about that also.I really doubt if L-Carnitine supplements are available here,i'll try to find them.

ZAINI.

These small changes in Hb level are nothing to be alarmed about and I think most patients could show you similar changes over the months. Many factors affect Hb including hydration level,  illness, climate and altitude and unless you see some sudden drop, there is usually no cause for concern.

10 mg folic acid daily is a good dose, so I don't think a higher dose is necessary. Give L-carnitine a try (I take it myself as it can also help burn fat if overweight) and see if her Hb level maintains longer.

ZAINI,

You might be aware of it already that each time the blood donated by a person might have the Hb levels at different levels and might therefore fall lower or might be higher than you expect.

As Andy has mentioned the levels do NOT seem abnormal, it seems such levels are normal. You are a good example of a mother trying to give your daughter a better life and I think that's setting up an example for others too (Especially in Pakistan - may be other around you can get inspiration from you)

Hi Zaini

Please check this too on L- Carnitine
http://www.thalassemiapatientsandfriends.com/index.php?topic=892.0

Manal

Thanx Andy,Narendra and Manal,

This site always gives me hope,the thing is, i think i am passing through my bad days now a days ,at least this is what i think,i feel like i am not doing enough for my daughter,i want her ferritin to be controlled,and hb to be maintained,when her hb goes down she is like really cranky and irritated,and i can't see her like that,i want her to be a happy child,and i personally know how it hurts when you have low hb ,bcoz i,ve spent so many years of my life with low hb, all the bodily pains ,feeling down and dizzy,and even i sometimes feel that low hb makes me depressed,I am an adult,but i just feel like she doesn't deserve it,she is going through her childhood,and childhood is supposed to be the days of fun and good memories,and it hurts me real bad when i think that when she'll be older she'll have the memories of her childhood filled with needles,pump and medicines.Although she is very active,always playing,non stop talking she is participating in her annual sports at school on saturday,i hope she'll win .

Sorry for all this crap,but i hope i'll come out of this phase pretty soon,just pray for me.

ZAINI.

hi Zaini.
Tomorrow  will be better. you know you are doing the best you can for your daughter ,and she will grow up knowing that she is loved.children are resillient.
Its never as bad as we think .
go on    remember our little mate   it will do you good have a good laugh  and not to worry,
  for you

Kathy

Hi Zaini,

Don't get depressed with little setbacks in life. You know that you are a great mom and are doing the best you can.

So roll up your sleeves and give little Zainab some milk and cookies and get her in training mode. We want a Gold medal!

Zaini, you are a great parent and i am sure that God will reward with everything you wish for
Manal

Zaini,

I am reading your posts for quiet some time. I truly believe you are doing the best for your child and take great lengths to do more. I see you don't want any stone unturned to get the best for Zainab. She is very lucky to have a mother like you.

First of all, you have to admit that you are doing best for Zainab (we all do).

Second, Its okay to feel little worried when you see the unexpected results, we all do. I think this time you are worrying too much, Zainab numbers are just fine. In my opinion (may be wrong) you are somewhat frustrated because Zainab results didn't show up to your expectations, you are worried if you are doing enough or the doctor is vigilant enough. JUST RELAX, everything is fine, and you know its a temporary phase and you will come out of it.

Hope this helps.

Hi Zaini,

I was reading thru your posts and as everyone said before me, you are a wonderful mother and very vigilant about zainab. So, you are doing everything right and so, please relax....everything is fine, everything is under control.

Also, I want to mention from the day I read your motto "Nothing can stop u unless u want to be stopped", I say it aloud when I feel depressed and it gives me immense strength to move forward. So, please say this aloud.....and I am sure you will get back your strength.