Iron and the lungs

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

manal

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  .

Zaini.

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  .

Zaini.

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)

maha

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

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

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!

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

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.

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   .

Zaini.

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

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.

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.

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

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