Thalassemia and iron overload

Hi there from Poland.

I am new member here, so I have many questions about thal.
Actually I got the test results today.
Here they are:
A2 hemoglobin:  5.15 % (normal range: 1.9-3.5)
Fetal hemoglobin = 1.3 % (normal range: below 1%)
Hemoglobin electrophoresis is due in one week.

Based on these results I assume I have Beta Thal. Based on morphology and other symptoms I guess it is the minor, not the intermediate.
I went to the hematologist today. It was professor in paid healthcare (you have to wait three months to get to hematologist in public healthcare). And he proved he was good for nothing...
As most doctors I met so far...

Now the explanation, why I post in this particular forum and why I was so angry with this doctor...

I was diagnosed about year ago that I have so called fat oxidation disorder. You just can't burn fats in muscles. This is genetic disorder - one of the enzymes that burn fat is missing. This causes accumulation of harmful by-products (they are free radicals) from incomplete fat oxidation cycle. The cell has to get rid of these free radicals.
One of the official reccomendations in this disorder is: "Do not eat red meat. It contains iron and iron is a free radical, which has to be taken care of in the same way as with the harmful by-products.".
That rang a bell. I always had elevated serum iron level. This was frequently disregarded by many doctors, while I was still seeking diagnosis for this fatty oxidation disorder.
Now one thing led to another and I ended up with thal diagnosis too.

Other tests results:
Iron: 177 ug/dl (normal: 50-120) (this used to be three times higher than mean normal value, ie. 250)
TIBC: 484 ug/dl (normal: 250-450)
Ferritin: 128 ng/ml (normal: 30-400).

I explained to the doctor that iron that high may have detrimental effects on me, but he said it is not possible anyway (as if he knew about my disorder...).
He argued that the only thing that counts in iron overload is elevated ferritin (which is normal in my case), so if I do not have ferritin elevated, then I do not have iron overload. Explaining that in my case iron level is that what counts did not help...
When I came back home, I found this (http://www.emedicine.com/PED/topic2229.htm):
For example, patients with β thalassemia intermedia who are not receiving blood transfusions have lower ferritin levels than those with β thalassemia major who are receiving regular transfusion regimens, despite a similar iron overload. In the latter group, hepcidin allows recycling of the iron from the macrophages, releasing high amounts of ferritin. In patients with β thalassemia intermedia, in whom the macrophages are depleted despite iron overload, lower amounts of ferritin are released, resulting in a lower ferritin level.

So it looks like you can have iron overload and still not have ferritin level elevated.
Also, if I am heterozygous for one of the hemochromatosis genes, I may be accumulating iron even more quickly, because it is already elevated.

Summing up: oversensitivity to iron, elevated iron level due to thalassemia and it looks like I have to be my own doctor.
What do I do now?
What test should I do in order to confirm that this higher iron level is harmful for me?
Maybe TAS (Total Antioxidant Status)?
What other tests can I do to confirm thal? I guess I could do genetic testing.
What drugs can I use to lower iron level? (I know home remedies - green tea and resveratrol)
I will have to pay for these tests, but I can afford most of them (well with difficulty, but what can you do), so this is not a factor here.
I am sure that some of the answers to these questions were already given in this and the other forums. I will try to browse through these answers.

Last, but not least, the symptoms.
Symptoms of fatty oxidation disorder: muscle pain.
Symptoms that I associate with iron overload:
- joint pain
- severe musous membrane dryness
- cold intolerance
- paresthesias

So this has to be it, because I could not find any other condition that could cause all these symptoms for many years now.

Thanks for all the answers.

Hi Bigg,

Your HbA2 and HbF levels both do indicate thalassemia minor. Your iron levels are all around the high end of normal, but as you said, these readings may not accurately reflect your iron load. This can be determined through liver scan or biopsy. Even in transfusing patients, iron is not adequately measured by ferritin tests alone. These tests are used more for comparison from test to test, rather than as a final word on iron load. I will give an example. A dear friend of mine in Germany has had excellent care for thalassemia and has faithfully used chelating drugs for many years. Her ferritin tests have always been very good. Yet, recently she was diagnosed with iron overload in her heart. There was never any indication in her ferritin tests that she had any iron problem. She is currently undergoing aggressive combination iron chelation to reverse this problem. Too many factors affect serum ferritin results and they do not tell how much iron is bound in tissue and organs. A liver MRI or biopsy can confirm whether or not you have developed any iron overloading. Do you have any symptoms of iron overloading? Have you noticed any change in skin tone? Any reduction in heart function? Anything that indicates iron may be a problem?

Even without any serious iron overload, the damage iron radicals can cause should not be taken lightly, as they have been implicated as contributors to cancer. You mentioned green tea but I would also suggest the supplement IP6, also known as phytic acid or inositol hexaphosphate. It is a member of the B complex family and is found in the bran of grains and also every cell in your body. It is a natural iron chelator and also a powerful antioxidant. I would also suggest you investigate the use of the supplement, L-carnitine, which helps to break down fats. In addition, a low fat diet can be of help (in my opinion, far more help than lazy doctors can be). You probably should also consider finding a new doctor who actually will make an attempt to understand your condition.

Thal minor does seem to exacerbate other problems, so it may be adding to your symptoms. Finding a doctor who understands both health issues may be difficult, but it is not impossible to find doctors who are willing to listen and learn. Yours appears to not be interested in learning anything.

Thank you for the reply, Andy.
It confirmed, what I have read here and there in scientific papers, but it is hard though to put it all together and draw conclusions.
About ferritin levels not reflecting iron load in body - can ferritin be *that* low as mine and I'd still have iron overload? How low was your friend's ferritin?
This is kind of stupid question of course because everybody is different, but I just need to know a number, so I could tell my doctors, that this is really possible.
An example of such a case (low ferritin level, but still iron overload) with numbers would be helpful (anyone out there... ?).

>Do you have any symptoms of iron overloading?
That is a good question. Usually I don't feel well, but it is hard to distinguish between symptoms from iron overload and fatty oxidation disorder . However it is established that with a proper treatment (diet and drugs) you can have normal life, without any symptoms and pain.
My doctors for metabolic diseases and I implemented such a treatment, and it did not bring expected effects on me.
So I started looking for the cause (of course my doctors disaproved and told me that I have to cope)... and it looks like I found it.
This has to be it, because I can't see any other irregularities in my tests (and I did almost any possible test, well, at least half of the tests from the hospital's list). 7 MRIs, but none of them of liver...

Perhaps the symptoms are not caused directly by iron overload, only thallassemia itself. I see 4 possible mechanisms:
- hypoxia (which causes another disturbances in fat&glucose metabolism, lactic acid buildup -> pain)
- inability to produce hem in cells other than erythrocytes (don't know if this is possible, but hem takes part in many matabolic reactions)
- excess erytropoetin (have to investigate on that)
- overall stress on the body
These still need a lot of investigation...

About possible overload symptoms, these are as I mentioned above:
- joint pain
- severe musous membrane dryness
- cold intolerance
- paresthesias
And I just rememberd
- glucose intolerance (3 results around 105 when normal range is 60-100, I guess that is a pattern)

>Have you noticed any change in skin tone?
Now that I think of it, many people tell me that my skin under eyes is brown, my face is yellow. Hmm...
My mother has brown rings in her eyes. Can it be a symptom for her (she has similar blood morphology as I have, so...)?

>Any reduction in heart function?
About 2 years ago palpitations started... Quite frequently (1 a day?), they last for 10 seconds.


About IP6.
Does it chelate iron only from the GI (gastro... something) tract (not allowing iron to be absorbed into body) , or it chelates from the whole body (so it actively removes iron from the body) ?
I read yesterday about IP-6, and the link

http://www.webvitamins.com/Nutrient.aspx?id=963

in this thread:

http://www.thalassemiapatientsandfriends.com/index.php?topic=653.0

says that it only works in the GI tract.
IP-6 would be beneficial for me in another way - it provides phophor(ylate) groups to the muscles, so they can work more efficiently.
Also this short chain fatty acid butyrate which is used to increase fetal hemoglobin would be beneficial for me in two ways - fetal hemoglobin increase and I can probably burn it without any problem.

I am already on carnitine and a low fat diet.

So, now I have a few ideas of tests, that I could do:
- TAS (don't know if it has any diagnostic value...)
- spleen ultrasound
- genetic testing for thallassemia (is the gene HBB right for the testing, or is there another gene?)
- other tests for thallassemia, if I find any. Fortunately I made friends with one of the lab technicians in hematology center, and she has already told me more than this hematologist doctor. Unfortunately I can't find any guide about the diagnostic path, i.e. which tests should be made based on previous results.
- Liver biopsy (seems unavoidable, at least to keep peace of mind, though it will be hard to make it happen without doctors' approval)

After that I will be trying to start treatment:
- Wheat grass (unfortunately looks like I will have to grow it myself  )
- IP6
- Resveratrol
- folic acid (can deficiency of other B vitamins be also a "cause" (well, it is not a real cause) for thallassemia?)
- low dose butyrate (if I can get any...)
And we'll see what happens.

I was and am a little overwhelmed by all this, but this site gives some hope...
Thanks for that.

Hi Bigg and welcome to the site

About ferritin levels not reflecting iron load in body - can ferritin be *that* low as mine and I'd still have iron overload? How low was your friend's ferritin

Please check what Professor Ali Taher said about your question in this link

http://www.thalassemiapatientsandfriends.com/index.php?topic=1702.msg14154#new


hope this answers your question, good luck

manal

Thanks, Manal.
That is exactly what I needed to confirm my suspicions.
It means that you may have your ferritin level lowered twice or even more (1200/500 = 2.4) than it would show if it was a real indicator of iron overload...

I read some posts and I see that liver biopsy is "no good". Looks like I have to take a leave of absense and find me FerriScan abroad. They do not do that in Poland. They do not even do genetic testing on a regular basis for thal (only for scientific research). How pathetic is this? So, despite my efforts, I am helpless (and frustrated of course).
Does anybody know the price of FerriScan in Great Britain, Germany, Italy or any other country? (they will not refund it in Poland, I'm sure).
Where would be the best place to go in these countries, if I decide to go?
I was also looking for SQUIDs in Poland, but I can't find any.

Serum ferritin tests are not considered to be accurate and are of more use as comparisons from one check to the next. Its value for testing for hemochromatosis is limited.

Serum ferritin has many false positives (because it is an acute phase reactant) and too many false negatives to be of any significant value as a screening test. However, if a patient is found to have an elevated ferritin, a transferrin saturation study should be performed. It is important to note that all patients with iron overload may not have hereditary hemochromatosis; indeed some patients may have secondary iron overload due to excess iron, hemoglobinopathies or a dysmetabolic iron overload state.

Biopsy and MRI are the standard methods. SQUID (Superconducting quantum interface device) is available in two locations in the US, and in Hamburg, Germany and I think also in Torino, Italy. It is the gold standard of heart iron measurement. T2* is used in more locations and uses the heart MRI to measure iron concentrations. You can read about this at http://www.thalassemia.org/sections.php?sec=2&tab=10&sub=204

Ferriscan technology is now being used with MRI to get a very accurate picture of iron concentrations in the liver. You can contact Sylvia from Resonance Health at sylviag@ferriscan.com for information on connecting your hospitals with the people who market Ferriscan.

Liver biopsy is often used but I am prejudiced because a friend of mine died from a blood clot after having a liver biopsy. This is a rare occurrence. but there is a slight risk. I have a hard time recommending biopsy and realize it is my own experience that shades my thinking.

I know there's more questions here but it's after 3 am so they will have to wait for now.

> I know there's more questions here but it's after 3 am so they will have to wait for now.
Well, these questions can surely wait, as I am focusing on getting FerriScan now.
I contacted FerriScan, and I think there are some possibilities, we'll see.

On another matter (maybe I should start another thread?).
I was wondering if thals have to have weak immune system by definition, or it is just a result of these nasty circumstances.
I read in one of the scientific papers about hemochromatosis something like that:
Bacterias need to obtain iron from the host in order to survive. They do it in many different ways - mainly by eating transferrin or ferritin.
Normally when bacterial invasion starts, the host's organism lowers iron level (transferrin or ferritin, I don't remember), but in case of hemochromatosis (same as in thals) this doesn't happen.
The result is that the immune system has to fight very strong bacterias and is exhausted.
And the bacteria are strong every time, every infection, because they have plenty of iron available.

So maybe the basic approach to enable immune system to fight the infection is to lower the iron level (somehow, I don't know how)?

Just thinking.

Bacteria and viruses thrive in an iron rich environment, as do cancers. The reason for all the research into IP6 has been because of its ability to inhibit the action of iron in cancer cells, because iron feeds these cells. But the effect on the immune system goes further than feeding bacteria, etc. All of the organs of the body become less efficient when the body has iron overload, and this weakens the immune system. Iron, like metals in general, is poisonous to the body once the body's needs are met.  Also, in answer to your question about IP6, it works throughout the body. Researchers were somewhat surprised to see how much actually makes it through the intestinal tract. We have also heard several reports within this group about how the skin became fairer in patients using IP6, a sign that iron is being removed from the tissue. One very important thing about IP6 is that it works in the body where it is needed. That is how it has been shown to fight cancer cells because it targets those cells. I would like to see some trials using high doses of IP6 to see what effect it has on heart and liver iron. Unlike desferal, IP6 has no trouble entering heart cells. And I do mean high dose. It does seem that some of the chelators being used are rather high doses, so why not try high dose with something that is far more innocuous and see how it performs?

I doubt you can figure a lot out until you get confirmation that you are thal minor. Bigg, do you know what your hemoglobin or hematocrit level is?

Well, my hemoglobin and hematocrit now:

HGB: 14,8 (normal 14-18)
HCT: 45,6 (normal 41-54)

But in 2003 these were:

HGB: 14,3 (normal 14-18)
HCT: 43,5 (normal 41-54)

In 2001 when I started to feel bad, I said to myself, that I have to do some excercise and take vitamins (including vitamin b complex). Pretty soon I was walking/jogging 10 kilometres a day.  So I guess, these values could be even lower. Still, they are on a low end.
To paint a full picture here, the other blood parameters are as follows (these are from 2007, after holidays, when I had quite a lot of physical activity):

RBC:  6,16 (normal 4,2-6)
MCV:  76,5 (normal 80-99)

So, every possible calculated indicator (Mentzer's...) points to thallassemia. You can find these indicators here:
http://www.cariboo.bc.ca/schs/medtech/RICE/thalassemia.html

Andy, when you ask me to confirm thallassemia minor, do you mean considering possibility of thallassemia major or considering that it can be no thallassemia at all?
But what else could this bel?
Can lead (or other heavy metal) poisoning cause this?

I had porphyrin test done, which excluded such possibility (you can never really trust these tests in this respect, because lead could accumulate in your organs, not in the blood, but anyway it doesn't affect my blood).
Porphyrin test showed slight elevation of every porphyrin (ca. 10%), which means increased production of hem, which can be explained by increased hemoglobin production. For lead poisoning these values are a few hundred percent greater than normal.

There will be a little more confirmation, when I receive the whole hemoglobin electrophoresis results, which show levels of HbA, HbA2, HbF, HbS, HbC.

Genetic testing is unavailable to me for now, can't find any lab.

Bigg,

When I said it needs to be confirmed I was talking about thal minor. Your hemoglobin and hematocrit are both normal (it took me years of effort to get my hematocrit to 45 and I am not a thal carrier but was anemic), your MCV is slightly low, your RBC's are on the high end of normal, but your HbA2 and HbF are both in range for thal minor, although the HbF is not very high. Hopefully the electrophoresis will shed some light on this. There are some other possibilities for high HbA2 and I also ran across a couple studies of people found to have higher than normal HbA2 of 4-5% without having any hemoglobinopathies. There is  a really good site that explains what many different tests mean. As far as HbA2, it has this info http://www.clinlabnavigator.com/Tests/HemoglobinA2.html

Hemoglobin A2 is composed of two alpha and two delta chains. The level of Hb A2 increases gradually through the first year of life at which time adult levels are reached. Elevated levels (3.5 7.0%) of Hb A2 are seen with beta thalassemia trait. Several abnormal hemoglobins including Hb S, E, C and O may cause spurious elevation. To avoid misinterpretation, hemoglobin electrophoresis should be run on all samples. Hb A2 may be increased with megaloblastic anemia and decreased with iron deficiency anemia.

Adult reference range is 0.0 3.5%.

For general reference http://www.clinlabnavigator.com/Tests/Hemoglobin.html

Reference range is 13-17 g/dL for men and 12.0 -15.0 g/dL for women. Hb levels below 6.0 g/dL are considered critical values.

Today was a good day.
I got results of hemoglobin electrophoresis. They confirm the previous results (A2 and F above normal) and no other hemoglobins present.

Then I discussed these results with lab technician.
Then I discussed with hematologist and she actually took interest in my case (finally someone!!!).
They both agreed that it must be thallasemia.

We also have a theory, why my hemoglobin content is so high.
This is because my blood system works like crazy (and is overactive to some degree). And this is not good, because iron turnover would be high in this case. There are some flaws in this theory, so I will have a loooot of tests scheduled.

Then I ordered Puritan's Pride Resveratrol (gelatin capsules), IP-6 (gelatin capsules), and Green Tea liquid extract. I will break the capsules and spill the contents.

Now to the Wheat Grass Shots, and there is a problem...

Here, it reads:

http://www.grassfactor.com/supershots.htm#

The main difference is the long shelf life - at least two years. Fresh wheatgrass juice only lasts a few days under refrigerated conditions. Because scientific research has shown that green chlorophyll has virtually no biological function in the human body, we have omitted the chlorophyll from our product.

but right here, it reads:

http://www.grainmills.com.au/webcontent79.htm

"I am analysing the structure of wheat grass and its similarity with blood. The solid content of wheat grass juice contains 70 per cent chlorophyll, which has the same atomic structure as haemoglobin. The only difference between the two molecules is their metallic atom content. While the haemoglobin molecule consists of iron, chlorophyll one is made of magnesium," he informed.

It seems very credible, that chlorophyll is responsible for the good effects of wheat grass. That's what the doctor from India said...
I've read posts on the forum to find more info, but still I don't know...

How do you solve this puzzle?

Dr Reynolds came to the conclusion that it is not chlorophyll which is responsible for the properties of wheatgrass because the properties remain when the extract is made and the extract contains no chlorophyll.

http://www.grassfactor.com/Chlorophyll_demise.pdf

Returning for a moment to the chlorophyll discussion, where chlorophyll degenerates after juicing and is not absorbed, the grass juice factor appears to be absorbed and to retain its stability and efficacy for years – perhaps indefinitely. That is, grass juice factor without chlorophyll is a healing agent. However, because the two substances are inseparable except by degradation of chlorophyll, it is not possible to have chlorophyll without the grass juice factor also being present. In other words the factor is always present, but chlorophyll is not. Therefore, in my view it is most likely that the grass juice factor is the actual healing agent.

A bone marrow aspiration can tell whether you have abnormal bone marrow activity. This would be able to confirm if your bone marrow is working overtime to keep your Hb high.

Hmm, this one's interesting:

http://www.indianpediatrics.net/june2005/june-618-620.htm

They speculate that wheat grass properties indeed do not depend on chlorophyll...

They also recalculated the original results to show that wheatgrass was beneficial to all children, even if  this effect was not very intensive. The original results were a little more cautious.