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HbF Gene Variant Linked to Moderated symptoms of beta-thalassemia

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Andy Battaglia:
Hi Manal,

Because (so far) fetal hemoglobin inducers don't raise the HB anywhere close to enough to eliminate transfusion dependency in majors, the bone marrow would remain overactive, leading to bone expansion. However, with intermedias, the hope is that by raising the Hb a point or two, that it be sufficient to suppress bone marrow expansion. That is one of the main criteria for deciding if an intermedia needs transfusions. If the condition can be managed without significant bone marrow expansion, then transfusion is usually avoided.

The problem with understanding fetal Hb concentrations is that it can be confusing when you talk percents rather than actual hemoglobin volumes. The Hb value is an actual total of the hemoglobin whereas the percent of fetal Hb is simply the percent of the Hb that is HbF.

If the Hb is 3 and the fetal Hb is 70%, 2.1 of the 3 is HbF. 70 % sounds like a lot but 2.1 doesn't. Now if the total Hb is 8 with the fetal Hb  raised to 30% the total HbF is now 2.4 even though the per cent of total Hb is much lower. If an increase in HbF doesn't raise the total HB, it means the other hemoglobins have actually dropped.

Hydroxyurea is unique among the fetal hemoglobin inducers in that it is a bone marrow suppressor, beyond what raising the Hb level will do to suppress bone marrow activity. This actually makes it less efficient than it could be in raising Hb. The ideal inducer would raise the Hb high enough to suppress excess bone marrow activity by raising the Hb high enough to eliminate excess bone marrow activity.

Manal:
Thank you Andy, the example made it really easy to understand, but


--- Quote ---If an increase in HbF doesn't raise the total HB, it means the other hemoglobins have actually dropped.
--- End quote ---

1- any rise in HB F as a result of inducers will normally lower the other hemoglobins since they all should add 100% , right so this is expected

2- This brings another question, assume an intermedia took an inducer (hydra) for a certain time and the HB F increased with a certain percentage then stopped this medicne. Will his body maintain this increase in fetal HB??

3-When the percentage HB A is lowered due to taking hydra, will it increase again after stopping it ?

4- what is the importance of HB A2 to our bodies, shouldn't it be more easy to increase its amounts in the body rather than trying to switch on the gamma genes to produce the fetal HB

Too long, i know... :-\ :-\

manal

Andy Battaglia:
Manal,

1) No. A rise in HbF does not lower other hemoglobins. The total Hb will rise as more HbF is added to the total. You are getting confused by percentages. Percentages are not volume. They tell you how much of a specific volume of hemoglobin is which type of Hb. The percentage that the other hemoglobins will be is lower because they are now less percent of the total but their volume hasn't changed. The percentage of each type of hemoglobin does not tell you anything at all about the total volume of hemoglobin.

Take a glass of water to represent hemoglobin. If you have one ounce of water and add an ounce of juice (to represent HbF), then 50% of the total is juice, but you only have two ounces. If you take a 9 ounce glass of water and add the same one ounce of juice, the juice content is only 10% of the total of ten ounces, yet each glass contains the exact same amount of juice. The percentage doesn't tell you anything about the total volume. It is the volume of hemoglobin that is added by HbF induction that matters. The percentage that is of total Hb is barely relevant.

2) If you stop giving hydroxyurea, you can't expect it to keep inducing hemoglobin. The Hb will drop unless some other factor has changed. The percentage increase of HbF isn't what matters. It is the total volume of hemoglobin that matters. It would be nice if there was some way to just prime the pump, so to speak, and stimulate the hemoglobin production and stop giving the stimulus, but so far that isn't the case.

3) Hydroxy suppresses bone marrow activity. It is not a very efficient drug from that stand point. If you stop taking it, whatever the state was prior to taking it, should return.

4) HbA2 is made from combining delta and alpha globins. Not much is produced and unlike HbF, there is no point in human life when it is. There isn't anything to turn on as with HbF. A baby in the womb relies totally on HbF and the goal is to stimulate this again to produce enough HbF to compensate for the lack of normal adult hemoglobin (Hb). You are asking the delta gene to do something it has never done at any point in the life of a human, whereas turning the gamma back on is asking to do something that was active when the human was a fetus. It would be unlikely that anything could modify the delta gene enough to make a serious impact on total Hb.

Manal:
Thank you Andy sooooo much for your effort, it is totally clear now.

I hope that these gamma genes can produce more hb than it used to in the womb, to be able to compansate an adult rather than a a fetus

manal

hopefulmommy:
Hello All and Andy,

I am feeling absolutely disturbed with my daughters results.

Her Hb levels:

at 3 days - 17.3

at 21 days - 15.3

at 1 month 10 days - 11.7

I cant think anything to calm my self or stop worrying .

Should I start giving her wheat grass shots? What can I do.

My daughter is EBeta Thal, 95% HbF no HbA and the rest Hb E.

Please help.

Thank you so much.

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