Thalassemia Patients and Friends
Discussion Forums => Thalassemia-related Issues => Topic started by: Sharmin on February 20, 2009, 09:56:23 PM
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There is reason to believe that iron can settle into the lungs and interfere with lung function. Time to time I have heard of thals experiencing breathing issues - sometimes when the hemoglobin is low and that may be related to lower O2 and lower oxygen carrying capacity of red blood cells when the patient is due for transfusion. I do think that high iron content in the lungs can cause low lung function.
Little A had some issues with breathlessness last fall - and breathing tests showed that he had low normal results. Now that his iron levels have come down the levels have all increased to well within the normal range. Another test will be repeated in 6 months (at the same time as his next SQUID test) to see the relation between iron levels and lung function.
The solution to this - as well as any other iron related issues in the body is - chelation and antioxidants. Chelation to remove the iron from the body and antioxidants to bind free iron so that it cannot damage the lungs.
Sharmin
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The effect of iron on the lungs has been the subject of several small studies, with somewhat conflicting results.
http://radiology.rsnajnls.org/cgi/content/full/229/2/507
Although iron deposits have been found in the macrophages in alveoli and in the perivascular tissue of patients with ß-thalassemia major at postmortem examination (30,31), the relationship between iron deposition in the lungs and pulmonary dysfunction is unclear (31). The proposed mechanisms of airway obstruction in ß-thalassemia major include oxidative damage as a result of free iron deposition within the airway epithelium (10,11). This theory is supported by the identification of iron-laden macrophages and lymphocyte alveolitis within the bronchial mucosa and in bronchoalveolar lavage fluid, suggesting that free iron deposition is a toxic mechanism.
Other suggested mechanisms are bronchial hyperactivity (32) and chronic immunologic factors (6) related to blood transfusion and disproportionate and/or excessive alveolar growth relative to airway growth caused by hypoxemia or hypoxia, a chronic abnormality in patients with ß-thalassemia major (33). It is known that serum ferritin levels do not necessarily reflect total body iron stores because they vary during the process of chelation and because ferritin is an acute-phase protein as well as a product of hepatocellular damage (34). It is therefore not surprising that reports of correlation of serum ferritin levels with pulmonary function have been contradictory; some researchers have shown a positive correlation (3,6,7), while others have not (4,5,9,10).
Chronic low oxygen levels also play a part in lung function in thals and this is another reason why keeping the hemoglobin levels up is important.
It's really good to see these positive reports on little A's health and it's a testament to the value of compliance with the various areas of treatment. The comprehensive approach to thalassemia treatment goes beyond the transfusion-chelation routine to include all aspects of physical and psychological needs of the patient. This program of treatment can prove very costly, so many aspects will not be followed in other treatment centers and in fact, not all are followed even in the comprehensive centers themselves. And this is actually an area where we can serve an important function in the international thalassemia community by promoting the concepts and methods that are included in the comprehensive approach to thal care. There are many things that patients and parents can do for themselves to improve health once they have the proper knowledge, and we regularly see patients doing better with health issues when they follow the advice they receive here. We are seeing how important supplements are for thals and the drastic improvement in health that is seen when deficiencies are corrected. We see how much better patients do with chelation when they learn the proper methods and mental approach. There are many things we do that help to spread the concepts of comprehensive care and this is a low cost approach that has major benefits. We use this group to educate patients, parents and even doctors to help further the understanding of the many issues involved with thal and the many facets of treatment. Our promotion of the comprehensive approach to thalassemia treatment is already seeing results and the various posts we read here show that patients are becoming more informed and are effecting changes in their local treatment centers and even furthering the understanding of thal care among medical professionals. This is only possible because the members have been willing to learn and to share what they learn.
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Thanks for the info Sharmin and Andy,
Chelation is a necessary part of thal's life,but its really sad to see that sometimes people do not understand that,i met today two youngsters who think just ferriprox is enough for them,although they have high ferritin levels,above 3000,and i don't think ferriprox alone can lower it.
I really feel sad for them,they have a life,they can have a chance at life and they are deliberately loosing it.
One of the two youngsters's mom was there,and she said i can not force,he is old and won't listen to me,she was sad,i wish i could have done something for her.
Zaini.
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Zaini,
Chelation two days a week with desferal on top of the Ferriprox would be great. Try explaining to them that desferal is more efficient than Ferriprox at removing iron from the liver, so the combination provides more than Ferriprox alone can offer. Two days a week is not a major hassle and should be possible. Do your best to get them to understand how much they can do for themselves with a little more effort. Ferriprox alone would be fine if their ferritin was lower but they need to get to that point before they use just Ferriprox.
I love the thalpal spirit that takes the information gathered here and spreads it to others.
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Andy,
One of them is our forum member,but he isn't posting much,i asked his mum why and she said he is very busy with the job and everything.
Other patient was a girl,studying i university,around 20 years of age,i told her that if you don't want to use needles,and just want to take tabs,you can atleast switch to Asunra,but she gave me impression that she couldn't care less,its sad.i'll try to talk to them again when i meet them.
Zaini.
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Since we have gotten back from Oakland, in addition to our previous supplements - I am giving him L-carnitine and alpha lipoic acid - also I have him skip rope every day. I think that this will be good for his heart, lungs and his bones. He is actually liking it and has been working on various tricks that he can do now that he is getting better at it. I think that it will also increase his balance and coordination for his other sports.
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Skipping rope is an excellent cardio exercise and it is used by boxers to improve endurance and agility. It will serve him well when playing hockey.
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Andy,
You are so right in what you said about Ferriprox alone not being effective, as far as liver is concerned.
I have my personal experience to deposit here:
My ferritin has been around 100 for the past 4 years and on 2007 I decided to chelate only on Ferriprox.No desferal at all.After one year only on ferriprox I did an MRI, and it showed a light deterioration on Liver (from T2*37 to T2*33) which, of course, is o.k and normal as this rate is considered safe and with no iron at all. However only ferriprox could not maintain the standard of T2*37.
Seeing this I started desferal again 4 days a week, together with ferriprox of course.
I think combination therapy is a must.
Lena.
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Lena,
Its really amazing for me,also your iron level and your chelation regimen,why do you have to do so much chelation with ferritin which is below normal range? Is it ok,chelators can't be harmful with that low iron?
Zaini.
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Zaini,
One would think that having so low ferritin enables you to lower your chelation scheme. This is partly right. I have concluded that with 90-100 vials of desferal per month and 7 tablets of ferriprox per day, I have succeeded in keeping ferritin at around 100. I take only 5 vials of desferal each time, as when I take 6 or more my pulse is slightly up and it returns to normal, 2 hours after the desferal has ended.
This of course answers to your question,that chelators can be harmful once your body is free from iron. However, here we keep about the same chelation scheme even if we have a normal sf.
Once heart and liver are clear, chelation proceeds to other organs.Of course, if the chelators become toxic you should change the scheme.
Lena.
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Its really amazing for me,as i always thought that one can go off chelation once iron is that low :dunno.
Zaini.
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No Zaini,
the only case you go off chelation is when you are cured by gene therapy and even then you have to chelate for a while after gene therapy for your body to drive off all of the iron it has.
Lena.
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Can i conclude from Zaini and Lena discussion that
1- L1/kelfer should not be used alone no matter how your ferritn is????? So why some patients used them alone like Ashish, Sahil,....?
2- Once heart and liver are clear, chelation proceeds to other organs
Does this mean that the iron overload doesn't start with these organ but iron is loaded in all organs at the same time. So if i am free of iron in the liver and heart, this does not mean that the other organs are free??? How can we measure iron in other organs??? :huh :huh
manal
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Manal,
About your first question,as we have heard before desferal is good at removing iron from liver,and ferriprox at removing iron from heart,so if you take ferriprox alone,i think there will be a risk that iron will get deposited in your liver,there was a short period of time when we were busy with some domestic stuff and everything was a bit hectic,so Little Z was on ferriprox alone and her ferritin increased.And we have heard that people who kept their iron levels low and were chelating,stil found outl they had iron deposited in their organs,so its a tricky one :dunno.
Zaini.
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Hi
I would like to add another question here. Why does it take 30 odd years for the ferritin to go below 500? Since chelation is done according to body weight, why can`t well chelated children also reflect such figures. Sharmin son was around 900, but since he was chelating from such a young age, why wasn`t his sf below 500. There are a few members in this site who have low sf levels and they age between 30-40.
maha
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Zaini
What about people having allergy from desferal???? I thought that L1 chelates everything but with concentration on heart same as desferal chelates everything but with concentration on liver :huh :huh :huh
manal
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Manal,
Sorry for my poor explanation ,but i think you have the answer present in your question,desferal chelates iron with concentration on liver,thats why when L1 wasn't widely available,thals use to have high iron deposition in heart which unfortunately lead to heart failure,that's where L1 came in,which chelates iron with concentration on heart,and thus save thals from iron overload in heart and in the end heart failure.
About desferal allergy,thats why a chelator which worked in both areas was highly needed,and thats where came in exjade,which works solely.
I think Andy will be able to explain this better :huh .
Zaini.
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Maha,
Little A's ferritin increased after he had to go through that antibody problem,where he was being hyper transfused,and what lena said got me thinking that ferritin is not the true indicator of how much iron is present in the body,so if a person has low iron we can not say that he or she won't have iron in organs at all.
Again you'll have to wait for Andy's reply for clarification :huh .
Zaini.
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Hi Zaini
Does that mean if Little A had not developed antibody issues his SF would have been below 500 by now. If chelation is begun at an early age will this iron still load in the organs. Who would have imagined that I would hate this one metal that gave me such a super and secure childhood( my dads a dealer in iron and steel) :wah
maha
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Dear Maha,
Little A's ferritin was maintained at 900 at a very low dose of exjade - he was transfused every four to five weeks and he received desferal for 10hrs a week 3 times a week. His dose of desferal at the age of 6 was that of a 3 year old. Because he started chelating at 18 months of age, by removing iron from the plasma early in his life we were successful in preventing iron from building up in his body.
The liver is generally the first place that iron is stored (this can vary to some degree between individuals). Using desferal early can prevent iron from building up in the body. When my son was 8 1/2 yrs (May 2006) old his ferritin was still 900 - it was after this age that the antibody problem started and the hypertransfusions started. In June of 2008 his LIC increased to 2880.
This tells me that his iron levels were not this high for a very long period of time - as they must have built up over 2 years probably reaching values over 2000 in the second year. What protected him is that the he was not exposed to the high levels for very long and that he was on antioxidants such as IP6 by the time his iron levels would have built up. I wish that I had taken him to Oakland much earlier so that his iron levels would never have gotten so high - but I am glad that they are back down again.
Another why we often hear of older patients rather than young ones having really low ferritins is the amount of chelation that they can tolerate. Little A was on desferal - which is typically not given for ferritin lower than 1000. In fact little A was taken off of desferal for a month at a time a few times when he was little because his ferritin was very low and the desferal was causing ringing in his ears. Excessive desferal can interfere in growth in young children so they like to keep to a minimum.
With chelators such as L1, exjade and combination therapy it is now possible to get to iron levels below 500 - and it is adult patients who have generally been taking doses high enough to get their ferritin levels so low. Giving such high doses to young children would interfere with growth. I believe that if I agressively chelated my son with exjade and desferal 7X a week 12-15 hours a day - and if his transfusion requirement remained low - that I could get his ferritin levels below 500 - however I don't want to risk the side effects of the drugs.
I hope that my explanation makes sense.
Sharmin
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Hi Sharmin
Yes, your explanation definitely makes sense. I had read someplace that it is dangerous for growing children to have SF levels very low. Infact chelation should be intervened if sf levels continuosly drop below 500.
thankyou
maha
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Oops, what is "skip rope"??? And what is alpha lipoic acid ?
I can only dream by hearing of a ferritin of that level. I have never come below 2000 since I started with this aggressivie deironing match 5.5 years ago. I have decided that I will only let them measure my ferritin once in the three months - since it is already for a year aroun 2500.
L1: I know a Dutch patient who get her ferritin level at 500 while only taking L1. Recently she was put on a real transfusion sheme. In her case two bags every five weeks She has never had regular transfusions before. But, her doctor let her stop taking L1 when she reached the 500. After that she started with this transfusion scheme. I have not done anything with my pk def. group in Feb due illness, but I will give awaraness in March again. Also, we have a new member with AIHA. Have someone every heard of that? She is treaten by prednison, but I am not sure what it is caused by. Dinner is ready, Adios!
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Skip rope is jumping rope. A jump rope, skipping rope, or skip rope is the primary tool used in the game of skipping played by children and many young adults, where one or more participants jump over a rope swung so that it passes under their feet and over their heads.
http://altmedicine.about.com/od/alphalipoicacid/a/alphalipoicacid.htm
What is Alpha Lipoic Acid?
Other names: lipoic acid, thioctic acid, ALA
Alpha lipoic acid is a fatty acid found naturally inside every cell in the body. It's needed by the body to produce the energy for our body's normal functions. Alpha lipoic acid converts glucose (blood sugar) into energy.
Alpha lipoic acid is also an antioxidant, a substance that neutralizes potentially harmful chemicals called free radicals. What makes alpha lipoic acid unique is that it functions in water and fat, unlike the more common antioxidants vitamins C and E, and it appears to be able to recycle antioxidants such as vitamin C and glutathione after they have been used up. Glutathione is an important antioxidant that helps the body eliminate potentially harmful substances. Alpha lipoic acid increases the formation of glutathione.
Alpha lipoic acid is made by the body and can be found in very small amounts in foods such as spinach, broccoli, peas, Brewer's yeast, brussel sprouts, rice bran, and organ meats. Alpha lipoic acid supplements are available in capsule form at health food stores, some drugstores, and online. For maximum absorption, the supplements should be taken on an empty stomach.
AIHA is autoimmune hemolytic anemia.
http://www.merck.com/mmhe/sec14/ch172/ch172f.html
Autoimmune hemolytic anemia is a group of disorders characterized by a malfunction of the immune system that produces autoantibodies, which attack red blood cells as if they were substances foreign to the body...
There are two main types of autoimmune hemolytic anemia: warm antibody hemolytic anemia and cold antibody hemolytic anemia. In the warm antibody type, the autoantibodies attach to and destroy red blood cells at temperatures equal to or in excess of normal body temperature. In the cold antibody type, the autoantibodies become most active and attack red blood cells only at temperatures well below normal body temperature.
Treatment
If symptoms are mild or if destruction of red blood cells seems to be slowing on its own, no treatment is needed. If red blood cell destruction is increasing, a corticosteroid such as prednisone Some Trade Names
DELTASONE
METICORTEN
is usually the first choice for treatment. High doses are used at first, followed by a gradual reduction of the dose over many weeks or months. When people do not respond to corticosteroids or when the corticosteroid causes intolerable side effects, surgery to remove the spleen (splenectomy) is often the next treatment. The spleen is removed because it is one of the places where antibody-coated red blood cells are destroyed. When destruction of red blood cells persists after removal of the spleen or when surgery cannot be done, immunosuppressive drugs, such as cyclophosphamide Some Trade Names
CYTOXAN
or azathioprine Some Trade Names
IMURAN
, are used.
When red blood cell destruction is severe, blood transfusions are sometimes needed, but they do not treat the cause of the anemia and provide only temporary relief.
We are all familiar with this by the way, as little A has been dealing with the warm autoantibody problem for some time. In the case of little A, his AIHA was brought on by the reaction of his body to some transfused blood. The reason we promote genotyping of blood (even though most centers will not yet do this due to cost...and one wonders how short-sighted this is, because long term correction of this problem is quite costly) is because it is less likely to develop this condition where the body attacks its own red blood cells if the blood is matched to antibodies native to the patient, rather than including the antibodies that are acquired through transfusions, as is done in phenotype testing. In the case of little A, a new treatment has been used. This is probably the first time this has been used in a thal with an autoantibody reaction causing hemolysis, and was the result of a long ongoing discussion between Sharmin and myself on how to treat this issue, after steroid treatment proved ineffective. Once again, we made be a little further along in our understanding than much of the medical profession when it comes to treating thalassemia and its associated problems.
Incidentally, this article mentions the use of cyclophosphamide for extreme cases. I recently posted about a case where cyclophosphamide was used in a two year old with hyperhemolysis whose hemolysis could not be explained by antibody activity. The treatment was successful. (I knew I would soon be referencing that post).
http://www.thalassemiapatientsandfriends.com/index.php?topic=2611.msg24213#msg24213
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Sharmin,
I have brought up a point here that needs investigation. We have learned that even the Comprehemsive centers are not regularly doing a genotype matching for blood due to the added costs involved in genotyping. Can Oakland give you a cost comparison between genotyping and the cost of dealing with antibody issues. This cost would have to include the cost for more frequent transfusions along with the cost of treatment of the antibody issue. In the long run, is not genotyping blood really cost effective? Little A has gone through a very expensive treatment using IVIG and rituxamab and he may need repeat therapy. It's hard to believe that genotyping his blood wouldn't have been cheaper in the long run, to say nothing of the quality of life issues that in my opinion, should be included in the cost.
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Dear Maha,
If chelation is begun at an early age will this iron still load in the organs.
I think thats the key,when Little Z started transfusing at the age of three,after one year her S.F reached 1700,and it was a jump,like one month we checked it was below 1000,and second month it was 1700,she had a severe cold at that time and i didn't know that it can effect her S.F levels,Her doctor did tell me that this can effect SF levels but never asked me to re check it,and i was scared by the number so we started chelation,but now i think that who knows it if it was better for her :dunno .
Zaini.
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Andy,
I was told in Oakland that the benefits of genotype testing far outweigh the costs of managing antibody problems in the future. Antibodies don't occur in all patients, but when they do they are devastating. It is like using a car seat for babies in a car accident - if you don't use a car seat and don't get into an accident you feel that you did not need it. In the case that an accident occurs the effects can be devastating and having had a car seat could have preventing the terrible consequences.
Andy, would cyclophosphamide something we may consider for our son?
Sharmin
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I would not consider cyclophosphamide unless other methods don't work. Cyclophosphamide is a chemotherapy drug with harsh side effects and its use in hemolysis is very experimental at this point. However, if the current treatment proves ineffective in the long term, it would be something to talk to Vichinsky about.
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Manal,
1. It is better ferriprox not to be used alone. You get better results when used in combination with desferal.
2. Of course iron is spread all over your body. As far as I am aware - and everyone, correct me if I am wrong - iron cannot be measured in the rest of the organs. During one of my MRIs I asked for the pancreas iron to be measured but they told me it is difficult to measure it. I think only the glucose tolerance test can show whether pancreas is free of iron. And of course, there is iron concentrated in your endocrine organs,bones,skin and so on.
And Maha,
do not forget that every blood unit we take has sf 200. So if you take 2-3 blood units per month, the sf goes up to 400-600 per month alone, not including the stock you already have. How can you lower this sf if you stop chelation?
Lena.
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From my understanding, because iron is stored in the liver - liver iron concentrations have been measured and recorded for many years. Also, because heart failure is a major risk in thalassemia - Dr. Wood created the T2* to measure iron concentration in the heart.
I suspect that software and data are not available to consider the overload of iron in other organs. I do believe that chelation with desferal and exjade lowers the overall iron levels in the body - that they would be reducing the iron stores in all organs of the body.
Desferal lowers plasma iron and is effective in removing iron from the liver and more slowly it does remove iron from the heart too. L1 does a good job of clearing iron from the heart. I believe that exjade, because of its ability to enter cells and tissue of the body removes iron from all organs in the body. I say this because my son's appearance has changed 110% - his skin is now a completely different color than it was when his iron levels were higher. It is so noticeable that people wonder if he had a tan when they last saw him which is now gone. Perhaps that is why combination therapy works so well. I think that we will resume combination therapy until his transfusion requirement is lower and his iron levels are below 1000. Then we hope to give him a break from desferal for a few years so that he can grow properly. Once he is grown (we pray that gene therapy is available during those years so it won't be necessary) - but he can consider adding desferal for a few days a week again.
Again, please note that only free iron can damage the organs and tissues of the body - therefore one should not go longer than 24-48 hourse without a chelator on board - also please take antioxidants to bind free iron so that it cannot cause damage.
Sharmin
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Andy,
Little A receives IVIG every 3 weeks, I am afraid of the risk of blood clots from the treatment. He gets a very small amount and his doc is thinking about cutting it down because his IG A, AG M, and IG g levels are in the normal ranges now. Also, it has been 3 months since we stopped his prednisone he may not require the same coverage from the IVIg anymore. What do you think?
Sharmin
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Thank you Andy,
I know I had read somewhere about it before. So far as I have been introduced in this new case is there only AIHA and nothing before. Personally I believe she must have an anemia which is unknow. I will post today or tomorrow an article about such case.
I will pass all the information to this person. If I have I'll give you an update.
The L1 story was based on the woman who wants a BMT. The latest information I have is from the beginning of Januari. Her sisiter can not be her donor :( and they have told her also that she is too old for a bmt (36yr). They are now looking for an other option. I start me thinking about undergoing a bmt for myself. What is the frontier of doing this? I have been told that I have to 10yr. But at that time I believe it was a ridiculous idea.
@ Sharmin: it is an interesting topic. I have never thought about lungs and iron before. I dunno, but 10years ago I underwent an MRI to find out how much iron there was in my whole body. After all this years I dont know of this was the real reason.
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Conflicting advice about chelation?
What needs to be remembered is that different drugs work differently with different people. About 16% of patients using Exjade find it ineffective at reducing iron load. Others people have tremendous success with Exjade, while others have average results. My late friend Gurleen (I really miss her), could not tolerate desferal and kelfer (L1) was totally ineffective for her. Many patients cannot use desferal often enough to keep their iron load down (Lisa). What does this all mean? You will see that with any and every drug, there are differences in how well they work with different patients. Some people like Poirot, do very well using only L1. Smurfette was doing quite well with L1 until her white cells dropped. Gurleen's ferritin was 12,000 on L1. Some people can do well with only one chelator but many people would be better off if they could use a combination.
There is no doubt that combination chelation is currently the best method for removing iron load from all organs. Every trial has showed that desferal and L1 together give the best results. The small trial that little A is in will give us some idea about the combination of Exjade and desferal. Perhaps the best chelating combination is not yet available. In my opinion, the safest and least bothersome chelation is not yet available and won't be unless funding can be raised to run the next stage of trials. This is starch DFO (desferal) being developed by Biomedical Frontiers Incorporated. This is a one hour IV treatment that could easily be taken while being transfused and the chelation effect lasts for up to one week. The potential for this chelating drug, especially when used in combination with other chelators (and it would be safe to use with all the current chelators in use) is great. A once weekly IV treatment could be combined with a reduced amount of another chelator to provide adequate chelation, and by doing so, this would also reduce the side effects of the other chelator. You can expect to hear me say more about starch DFO, as I believe this would be a Godsend to many patients who have trouble complying with chelation enough to keep their iron load in a safe range. I want to see this company get the necessary funding and I will continue to promote the development of this new chelator. The patients need it.
Sometimes patients have been able to take chelation breaks when their ferritin gets very low but this is only temporary. Lena is managing her iron load quite well and her program is working for her. I would not suggest any changes because it is effective. Each patient is unique and this is why individual treatment programs should be designed for each patient. When ferritin is in the hundreds, it does have to be regularly monitored and chelation dose adjusted if necessary, as chelation can cause harm if iron load is not above normal.
There are no simple answers and explanations for this topic. Chelating drugs do not work the same in each person and while some people may do well with strict compliance to one chelator, others may need a combination, either because the chelator they use is not sufficiently effective for them or they are not able to take a high enough dose to keep a correct iron balance, so combination is necessary (I think most patients fall into this category).
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Sharmin,
I agree that the dose of IVIG can be cut and possibly eliminated altogether. The understanding of how and why IVIG works is not complete and it is a powerful therapy, so it isn't something that you want to see a patient use indefinitely. With his levels back to normal, it is a good time to try reducing the dosage with the goal of stopping completely when indicated by stable levels in his body. Dealing with autoimmune disorders is still a guessing game and nothing is certain until you see results. Once things are reversed, we can hopefully see a reduction and possibly elimination of the need for the treatment drugs.