Thalassemia Patients and Friends
Discussion Forums => Thalassemia Minor => Topic started by: karoloydi on September 16, 2010, 07:09:04 AM
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Can our mild anemia be alleviated by increasing testosterone?
I found several studies that show that testposterone can increase erythropoietin. Erythropoietin will increase hemoglobin. This is a quite indicative study:
Testosterone regulates erythropoiesis in numerous mammalian species, including humans of both sexes (1). Excessive erythrocytosis is the most common serious adverse event associated with testosterone therapy in older men (2). However, the mechanisms by which testosterone stimulates erythropoiesis remain poorly understood.
It has been suggested that testosterone stimulates erythropoietin secretion and directly stimulates erythroid progenitor cells (3, 4). We showed previously, however, that testosterone dose-dependently increases hemoglobin and hematocrit, but without an associated increase in erythropoietin (5). In addition, testosterone has minimal proliferative effect on purified (CD34_) erythroid progenitors ex vivo (6).
We considered the hypothesis that testosterone increases hematocrit by suppressing the master iron regulatory peptide hepcidin, thus resulting in increased bioavailable iron. Hepcidin is a liver-derived peptide that binds to and degrades the iron channel ferroportin (7, 8). Increased hepcidin, in response to infection and inflammation restricts systemic iron bioavailability and results in mild anemia in chronic disease (9). Low hepcidin, conversely, is associated with increased iron absorption, increased systemic iron transport, and erythropoiesis.
To test the hypothesis that testosterone suppresses serum hepcidin, we measured serum hepcidin levels in a testosterone dose response study, in which healthy younger (19–35 yr old) and older (59–75 yr) men were administered a long-acting GnRH agonist to suppress endogenous testosterone production, along with varying doses of testosterone enanthate for 20 wk (10, 11). This design produced cohorts of subjects with graded, stable levels of testosterone within 4wkthat were maintained for 20 wk. This intervention resulted in dose-dependent increases in hematocrit and hemoglobin that were greater in older than younger men (5).
We measured serum hepcidin in serum samples from these men, and tested the hypothesis that age-related differences in erythropoietic response are related to the magnitude of hepcidin suppression. We also assessed whether early changes in hepcidin levels predict subsequent changes in hematocrit and hemoglobin.
Bachman E, Feng R, Travison T, et al. Testosterone Suppresses Hepcidin in Men: A Potential Mechanism for Testosterone-Induced Erythrocytosis. J Clin Endocrinol Metab:jc.2010-0864.
Context: The mechanisms by which testosterone increases hemoglobin and hematocrit are unknown.
Objective: The aim was to test the hypothesis that testosterone-induced increase in hematocrit is associated with suppression of the iron regulatory peptide hepcidin.
Participants: Healthy younger men (ages 19-35 yr; n = 53) and older men (ages 59-75 yr; n = 56) were studied.
Methods: Weekly doses of testosterone enanthate (25, 50, 125, 300, and 600 mg) were administered over 20 wk, whereas endogenous testosterone was suppressed by monthly GnRH agonist administration. Blood and serum parameters from each individual were measured at wk 0, 1, 2, 4, 8, and 20. Longitudinal analyses were performed to examine the relationship between hepcidin, hemoglobin, hematocrit, and testosterone while controlling for potential confounders.
Results: High levels of testosterone markedly suppressed serum hepcidin within 1 wk. Hepcidin suppression in response to testosterone administration was dose-dependent in older men and more pronounced than in young men, and this corresponded to a greater rise in hemoglobin in older men. Serum hepcidin levels at 4 and 8 wk were predictive of change in hematocrit from baseline to peak levels.
Conclusion: Testosterone administration is associated with suppression of serum hepcidin. Greater increases in hematocrit in older men during testosterone therapy are related to greater suppression of hepcidin.
Also this one:
http://bloodjournal.hematologylibrary.org/cgi/reprint/31/4/453.pdf
And this one:
http://bloodjournal.hematologylibrary.org/cgi/reprint/33/4/564.pdf
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In thal patients, the erythropoietin are muted so what is the benefit of increasing there number with no use. Actually increasing erythropoietin means that the bone marrow is exta active and therefore there will be more chances of getting bone deformity
The above study was done on NON thal patients and that is why the results may vary
manal
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I think what you say is trued for majors and intermedia thalassemics. But in beta minor I think increasing testosterone and erythropoietin would be beneficial.
I remember reading about an athlete that had thalassemia minor and has trouble performing. Then after administration of erythropoietin his performance improved as well as his hemoglobin. I ll try and find that article.
EDIT: Found it:
A 22-Year Old Division I Male Football
Player Diagnosed With Beta-Thalassemia
Minor Blood Disorder: A Case Study
O’Brien MS, Ransone JW, Smith KB:
College of Education, Oklahoma State
University, Stillwater, OK
Personal data
A 22-year-old division one collegiate football
player with no remarkable medical history complains
of fatigue and inability to recover from bouts
of exercise.
Physical signs and symptoms
The athlete presented symptoms of cardiovascular
(CV) deficiency (shortness of breath, irregular
CV endurance) for which, the team physician ordered
a blood work up including baseline levels of
comprehensive metabolic profile (CMP) and complete
blood count (CBC).
Differential diagnosis
Differential diagnosis of signs and symptoms include
iron deficiency anemia, sickle cell anemia,
beta thalassemia minor, hereditary leptocytosis,
minor heterozygous beta thalassemia intermedius
Results of diagnostic imaging/laboratory tests
After a baseline CMP and CBC were completed
revealing depressed levels of hemoglobin, further
tests were ordered by the team physician. Results
of these tests coincided with hypochromic
microcytic anemia. A sickle-dex was conducted
and was found to be positive. Results of the
hemoglobin electrophoresis conducted thereafter
indicated a depressed amount of hemoglobin A
(90%, reference 93.5%- 98.3%) revealing the betathalassemia
minor disorder. Additionally, initial
blood work presented low levels of blood erythropoietin
levels (4.7 mu/mL, reference 7.3- 27.7),
hemoglobin (11.8 g/dL, reference 14.0-18.0 g/dL),
and hematocrit (37.4%, reference 42.0- 52.0%).
Blood work conducted one week post Procrit®
injections exhibited elevated hemoglobin (16.1 g/
dL) and hematocrit (48.7%). Follow up measures
obtained one month post injections revealed
a marked decrease in blood erythropoietin levels
(3.8 mu/mL) and normal levels of hemoglobin
(14.9 g/dL), and hematocrit (45.6%)
Clinical course
To treat the beta thalassemia minor anemia, the
team physician prescribed the administration of
10,000 units of Procrit® (erythropoietin supplement)
according to the athletes body weight, three
times per week for one month to restore normal
levels of hemoglobin production, 325 mg of
Ferosul® (ferrous sulfate) and 500 mg of ascorbic
acid daily.
Deviation from expected
Thalassemia minor is a blood anemia characterized
by a genetic anomaly that affects the number of
hemoglobin proteins of a single red blood cell and
their ability to carry oxygen. Thalassemia minor
is not typically seen in the athletic population
and treatment for the disorder has not been
thoroughly addressed. In this particular case, the
prescription of Procrit erythropoietin was decided
upon to elevate hemoglobin levels and re- establish
the athlete’s oxygen carrying capacity to that of
normal levels required for athletic competition.
The athlete responded well to this treatment and
continued full participation in football activity.
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Thal minors could decrease or eliminate their symptoms through a good program of nutrition and supplementation. Taking Procrit could cause other serious side effects, so risks must be weighed in thal minors.
WARNINGS: INCREASED MORTALITY, SERIOUS CARDIOVASCULAR EVENTS, THROMBOEMBOLIC EVENTS, STROKE and INCREASED RISK OF TUMOR PROGRESSION OR RECURRENCE
Chronic Renal Failure:
In clinical studies, patients experienced greater risks for death, serious cardiovascular events, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target hemoglobin levels of 13 g/dL and above.
Individualize dosing to achieve and maintain hemoglobin levels within the range of 10 to 12 g/dL.
Cancer:
ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence in some clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers (see WARNINGS: Table 1).
To decrease these risks, as well as the risk of serious cardio- and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusion.
Because of these risks, prescribers and hospitals must enroll in and comply with the ESA APPRISE Oncology Program to prescribe and/or dispense PROCRIT® to patients with cancer. To enroll in the ESA APPRISE Oncology Program, visit www.esa-apprise.com or call 1-866-284-8089 for further assistance.
Use ESAs only for treatment of anemia due to concomitant myelosuppressive chemotherapy.
ESAs are not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cure.
Discontinue following the completion of a chemotherapy course.
Perisurgery: PROCRIT® increased the rate of deep venous thromboses in patients not receiving prophylactic anticoagulation. Consider deep venous thrombosis prophylaxis.
(See WARNINGS: Increased Mortality, Serious Cardiovascular Events, Thromboembolic Events, and Stroke, WARNINGS: Increased Mortality and/or Increased Risk of Tumor Progression or Recurrence, INDICATIONS AND USAGE, and DOSAGE AND ADMINISTRATION.)
http://www.rxlist.com/procrit-drug.htm
Procrit is usually used to correct the anemia in cancer patients after the course of chemotherapy.
Some doctors advise their patients to have these injections but no real benefits were confirmed
manal
manal
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Hi Karoloydi,
I am 31 years beta thal carrier. I also have elevated testosterone level which I found out recently. To be honest with you this is not helping me much.
I think because of testosterone elevation I start having irregular period, hair loss and hair growth in unusual places. My hemoglobin is 11.3. High testosterone level may give more energy but my irregular period is truly bothersome. It might be beneficial to male but I am suffering badly here.
Just wanted to share this info with you.
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WOW... MY FIRST POST. SO EXCITED!!!!!! THANKS TO EVERYONE ON THIS SITE... YOU'RE A GODSEND!!!!
OK, SO I AM A THAL MINOR W HEMOGLOBIN ABOUT 10.6-11.2. I AM AN AVID RACQUETBALL PLAYER, RUNNER, SURFER, ETC... BUT FOR OBVIOUS GENETIC REASONS I SUCK AT ALL OF THESE!!!! I NEED HELP... I HAVE TRIED EVERY SUPPLIMENT IN THE WORLD TO CORRECT THIS PROBLEM, SO PLEASE NO SNAKE OIL, AS WE'RE TALKING GENETICS HERE. THAT MEANS U CAN TAKE 5,000 MG OF FOLIC ACID TILL UR BLUE IN THE FACE... IT DOESNT WORK!!!!!!!!!!!!!!!!!!!!!!! I HAVE GONE AS FAR AS INJECTABLE EPO IN BIOLOGIC DOSES ENOUGH TO KILL A DUTCH CYCLING TEAM!!!! (YES, THAT ACTUALLY HAPPENED ONCE UPON A TIME). IT DIDN'T RAISE MY CRIT EVEN A LITTLE!! I'VE EVEN EXPERIMENTED WITH HU, A DRUG DESIGNED TO INCREASE FETAL HEMOGLOBIN, BUT IS A CHEMOTHERAPEUTIC AGENT (LONG TERM EFFECTS?). ANYWAY, I'M 47, AND NOT REALLY READY TO SIT ON THE COUCH N WATCH OPRAH. I'M INTRIGUED BY TESTOSTERONE. ANYONE TRY THIS YET? I HAPPEN TO KNOW THAT IM A LITTLE LOW ANYWAY, SO IM SURE I COULD GET A SCRIPT FOR THE GEL. BTW, I EAT VERY CLEAN, TAKE SUPPS, AND EXERCISE MORE THAN ANY NORMAL PERSON, SO I'M LOOKING FOR SOMETHING OUT OF THE USUAL. ANY INPUT APPRECIATED. I'VE ASKED GOD A MILLION TIMES A DAY WHY HE WOULD GIVE ME THIS CRAPPY DISEASE, BUT THEN I THANK HIM I DONT HAVE COOLEYS...
BLESSINGS,
PHIL
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I am no expert by any means, but after reading your post I did wonder if the real problem may be linked, quite simply, to your over-active lifestyle. I have read several posts on this site that describe how oxygen in the body is effected in people with Thalassemia. Could it be that you are exerting yourself to a point that your body simply cannot keep up in regards to oxygen delivery and production of healthy cells?
I know this is quite a different case and we still have not determined the exact type of Thalassemia that our toddler has, but when he is rested and wants to play he goes full force, no one would think anything is wrong (and he has severe iron deficiency in combination with the Thalassemia). It is the next day that we see the effects of his exertion, his body simply cannot keep up with the demands. I hope that this changes, and I really commend you for leading such a healthy and active lifestyle, just make sure all those efforts are really in your best interest...might be a case where you just need to scale it back a bit.
Best wishes,
Sarah
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I think what you say is trued for majors and intermedia thalassemics. But in beta minor I think increasing testosterone and erythropoietin would be beneficial.
I remember reading about an athlete that had thalassemia minor and has trouble performing. Then after administration of erythropoietin his performance improved as well as his hemoglobin. I ll try and find that article.
EDIT: Found it:
- Is there a source for the quoted abstract? I could only find a link to thalpal via Google search.
- Why did they give an iron supplement to a thal minor? Does that have anything to do with the epo supplement? I'm confused. [Seems they probably wanted to make sure there was enough iron to produce RBCs after the administration of the epo supplement.]
Thal minors could decrease or eliminate their symptoms through a good program of nutrition and supplementation. Taking Procrit could cause other serious side effects, so risks must be weighed in thal minors.
http://www.rxlist.com/procrit-drug.htm
In clinical studies, patients experienced greater risks for death, serious cardiovascular events, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target hemoglobin levels of 13 g/dL and above. Individualize dosing to achieve and maintain hemoglobin levels within the range of 10 to 12 g/dL.
The reason for this seems to be that the hemoglobin levels caused by a treatment with an epo supplement tend to not be stable and can go up and down quite a bit. I read an article in a German magazin (http://www.pharmazeutische-zeitung.de/index.php?id=3669) which stated that the levels take a 'zig-zag' course. Imagine a +/- amplitude around a certain desired level. Other than that, I probably think the increased stroke risk is also caused by the increasing hematocrit which usually follows the higher Hb levels in a patient. But I think this would always be the case if you increase the Hb levels, so it's not an 'isolated' epo risk. It's also there for testosterone users, for example.
Edit: The article also mentions that there are other types of epo supplements with a half-life period of 130 hours (Epoetin Alfa = 7 hours) that are able to provide more stable Hb levels.
Edit 2: If you see what the team physician of the football player did, I'm pretty sure that the often-mentioned examples like Pete Sampras Zinédine Zidane both had their minor symptoms treated with all kinds of supplements. And they would never be able to talk about that anyways, because that would probably mean they'd also have to admit to doping.
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For what it's worth, I've boosted my testosterone by injections to high normal - and it made no difference. Gave me energy and clarity, libido etc.
But the easy fatigue and lack of endurance and cardiovascular function, along with out of range low haemoglobin tests remain. And I mean remain untouched. They are literally identical to when my testosterone was tanked.
There are steroids besides testosterone, like boldenone, that are VERY well known for raising hematocrit and many athletes use, but that's a bit foolish and not a long term solution. Even if it was an improvement, that's more strain on your heart, which would cause you to have to donate blood to lower the hematocrit, which would bring you back to square one anyway.
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out of range low haemoglobin
The blood test you posted showed a pretty high hemoglobin value. Do you know how much that value fluctuates for you?
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The blood test you posted showed a pretty high hemoglobin value. Do you know how much that value fluctuates for you?
Oh to clarify I mean cell hemo sorry, not outward hemo. But in any case:
Yep I do know how much it fluctuates - not at all. Literally hasn't changed. In fact on my new test it's all even LOWER but by such a minuscule amount as to be of no significance.
I have a blood test from when my Testosterone was low, and a blood test as of last week showing just over high normal Testosterone (out of range, even) and the haematology on both from top to bottom is literally what I'd call identical. Not even my red cell count improved, which Testosterone is notoriously known to do.
EDIT: In fact here they are. First number is during low Testosterone blood test. Second number is 6 months on Testosterone - with it being JUST high out of normal range.
Hb: 159 / 155
Hct: 0.50 / 0.49
RBC: 6.2 / 6.2
MCV: 80 / 79 Both out of range low
MCH: 26 / 25 Both out of range low
MCHC 319 / 317 Both out of range low
RDW: 14.3 / 14.4
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You mean the MCV? Do you know why this could cause a pale skin? I had my hemoglobin at 14.3, but my MCV was only 69 and I'm also very pale. :huh Could this be a problem with releasing oxygen into the tissue? All the explanations don't mention the exact factor/mechanism that causes the pale skin... :dunno
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You mean the MCV? Do you know why this could cause a pale skin? I had my hemoglobin at 14.3, but my MCV was only 69 and I'm also very pale. :huh Could this be a problem with releasing oxygen into the tissue? All the explanations don't mention the exact factor/mechanism that causes the pale skin... :dunno
The MCH and MCHC particularly but also the volume. Yes, I believe it is primarily oxygen-related. And secondarily nutrient related.
You have to keep in mind that, this is why a specific hemo blood test is ordered, as there are more than 400 types of anemia, and countless types of hemoblogin which could be causing the issue.
For example - you could have an abundance of hemoglobin - but it is a type that is very poor at carrying oxygen.
You could have plenty of RBC's - but they could be poorly shaped and formed.
You could have a great type of hemoglobin - but very low levels of it in blood cells.
At the end of the day, it all results in starved oxygen in the blood which causes the breathlessness, fatigue and the pale skin (instead of the healthy pink/red of oxygenated cells).
And also the fact that cells are constantly destroyed with the spleen turnover mentioned elsewhere, stressing the body and causing it not to absorb the nutrients and minerals it needs elsewhere, also needed for the production of things like healthy melanin, vitamin D etc which also negatively affect skin tone.
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I don't think there are so many different types of hemoglobin that it would play a big role; afaik, mostly those that show up in a hemoglobin electrophoresis. I think I'm going to do this test soon and include a few other blood values in my next blood test, e.g. hemolysis parameters , thyroid glans (TSH is at 3; I should probably check FT/T 3/4) and hormones.
- Are there any specific hormones one could check that could cause the fatigue? Only testosterone?
- Is there only the hemoglobin electrophoresis or 'real' genetic tests that could show me the exact deletions etc.?
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I don't think there are so many different types of hemoglobin that it would play a big role; afaik, mostly those that show up in a hemoglobin electrophoresis. I think I'm going to do this test soon and include a few other blood values in my next blood test, e.g. hemolysis parameters , thyroid glans (TSH is at 3; I should probably check FT/T 3/4) and hormones.
- Are there any specific hormones one could check that could cause the fatigue? Only testosterone?
- Is there only the hemoglobin electrophoresis or 'real' genetic tests that could show me the exact deletions etc.?
From WebMD:
There are more than 350 types of abnormal hemoglobin.1 The most common are:
Hemoglobin S. This type of hemoglobin is present in sickle cell disease.
Hemoglobin C. This type of hemoglobin does not carry oxygen well.
Hemoglobin E. This type of hemoglobin is found in people of Southeast Asian descent.
Hemoglobin D. This type of hemoglobin is present in some sickle cell disorders.
Yep not hormones but things worth checking.
Vitamin D
Potassium
Iodine
Vitamin B12
Zinc
Vitamin C
Vitamin E
Thyroid
Testosterone (free and total)
LH/FSH
Estradiol
Prolactin
DHT
Growth Hormone
Adrenals/Cortisol
DHEA
I'm not sure on a complete DNA test. I would think that would be quite expensive.
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If even the amount of hemoglobin (as in: the blood value) doesn't tell us everything about how much oxygen really arrives at the tissue, what do you think could we do to determine it? Measure the oxygen saturation in the blood?
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If even the amount of hemoglobin (as in: the blood value) doesn't tell us everything about how much oxygen really arrives at the tissue, what do you think could we do to determine it? Measure the oxygen saturation in the blood?
I'm not quite sure what you mean. The hemoglobin and those values ARE measuring the oxygen saturation in the blood. The hemoglobin IS the oxygen transport vessel to the tissues.
If you nail down what's wrong with it, you have your answer of how much oxygen is arriving. Thus the whole basis of anemia, and the many different causes.
The only other issue would be if otherwise healthy cells are just being outwardly destroyed for some other reason - an auto immune disease or something. But that would also show on the hematology values.
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And what could be wrong with it? If what you said is true and the hemoglobin is a special variant, then the sheer amount of it in the blood would not tell us how much oxygen is actually being transported, e.g. x g/dL hemoglobin type abc vs. x g/dL hemoglobin type cde would not amount to the same oxygen transport capacity if what you said is correct.
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And what could be wrong with it? If what you said is true and the hemoglobin is a special variant, then the sheer amount of it in the blood would not tell us how much oxygen is actually being transported, e.g. x g/dL hemoglobin type abc vs. x g/dL hemoglobin type cde would not amount to the same oxygen transport capacity if what you said is correct.
It's just genetically wrong, and abnormal. Like trying to run a petrol engine (Hemoglobin A for example) on diesel (Hemoglobin Z for example). It's not fit for the job.
What TYPE of hemoglobin it is, is EXACTLY what tells its oxygen carrying capabilities, though I don't know the exact scientific way it is calculated. This is exactly how Thal is diagnosed via a hemoglobin test.
And then in addition, how much of it exists in the bloodstream, and then, how much of it exists IN EACH cell.
Also in regards to your other question about the genetic part, Wiki suggests:
That it is caused by mutations in the HBB (beta globin) gene on chromosome 11, inherited in an autosomal recessive fashion. The severity of the disease depends on the nature of the mutation.
Minor = Only one of β globin alleles bears a mutation. Individuals will suffer from microcytic anemia. Detection usually involves lower than normal MCV value (<80 fL)
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HBB blockage over time leads to decreased beta-chain synthesis. The body's inability to construct new beta-chains leads to the underproduction of HbA. Reductions in HbA available overall to fill the red blood cells in turn leads to microcytic anemia.
https://en.wikipedia.org/wiki/Beta_thalassemia
I think this part is for Major, but is the bold part not what we also experience with Minor? If there is enough hemoglobin to fill an average amount of RBCs, why would the body produce an above-average amount of RBCs and then fill them with less hemoglobin, leading to a low MCV value? This confuses me a bit. In my case there was apparently sufficient hemoglobin available (14.3), but the RBC count was way out of range (6.9) and the MCV was only 64.3 (-> MCH 20.7).
BTW: thanks for all your responses. It's great to see that kind of activity in the forums.
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https://en.wikipedia.org/wiki/Beta_thalassemia
I think this part is for Major, but is the bold part not what we also experience with Minor? If there is enough hemoglobin to fill an average amount of RBCs, why would the body produce an above-average amount of RBCs and then fill them with less hemoglobin, leading to a low MCV value? This confuses me a bit. In my case there was apparently sufficient hemoglobin available (14.3), but the RBC count was way out of range (6.9) and the MCV was only 64.3 (-> MCH 20.7).
BTW: thanks for all your responses. It's great to see that kind of activity in the forums.
Yes essentially, that is my understanding. The same or similar, but it depends on the severity, including the mutation. As it goes on to state for major: This is a severe microcytic, hypochromic anemia due to dual mutations, not just one. So the same form but much more severe. Again, there are also many causes of the same thing. The most common cause of microcytic anaemia is actually iron deficiency, as Thal is comparatively rarer. So plenty of oxygen in that case, but not enough iron = starving cells. Most of us actually have good iron levels - if even sometimes too much.
I guess that's just the nature of the beast, but it makes sense. Because if they are still poorly oxygenated due to mutation of the hemo, the body is essentially still starving for oxygen so it turns them over. They get destroyed by the spleen and the body then produces more red cells to counteract this. So you can end up with plenty of cells, maybe even plenty of hemo (or not enough to keep up), but still poor oxygen carrying capacity. I would presume this is also why some folk's symptoms fluctuate. There may be points where their blood work is lining up sufficiently (still not ideally) where they are scraping by with good cell count, good hemo and good volume before the turnover process reverts back.
Imagine the mutated hemo to be like water (iron) filled balloons with the ends tied up (mutated). They can't carry any oxygen because they are tied off. It doesn't matter if you even have an entire factory (red blood cell) full of them, no matter how many you have, they still can't carry oxygen well. And in the process of popping them (spleen) to try and make room for new balloons, that will hopefully be better, you end up with more balloons than you have air to fill them to begin with anyway (MCV). And they're still just filled with water (iron) and the ends are tied off (mutated) so they can't carry air well.
Ditto, good to research, discuss, learn and compare.
I was also watching an endocrinologist talking yesterday about this increase in Erythropoietin, and his understanding was that it is DHT that Test turns into @ the 5AR that can do it. However, I don't know if this is only exclusively in healthy individuals, as I have taken mildly methylated pure DHT in the form of Proviron with my Testosterone therapy before those blood tests, and as you can see it did nothing at all - even though my DHT did increase significantly.
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One point that needs to be made about hemoglobin, is that variant hemoglobins may not release the oxygen as readily. This is the case with fetal hemoglobin so, the total hemoglobin does not necessarily tell you how easily the body can access the oxygen that is carried by the hemoglobin.
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Yes this is the case with minors.
Normal or near normal RBC counts and Low MCV level, Why it is so? Even i want to know.
How to increase MCV levels in Minors? As normal MCV can increase stemina in minors.
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How can you increase MCV when a portion of your red blood cells will always be small? I don't think it can be changed. Minors don't have normal MCV. It is just a reflection of the fact that minors have defective red blood cells in addition to the good RBC's they produce, so the average MCV is less than normal.
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I thought the same, Andy. The question I have is: what defines the size of RBCs? Why do Minors produce regular and malformed RBCs at the same time? Is there a set ratio or would an decrease or increase of the RBC count affect the MCV? (I guess not?)
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Beta thal minors have one beta globin gene that is either deleted or mutated. This is the gene responsible for producing the small defective red blood cells that bring down the average size, which lowers the MCV. The other gene produces normal beta globin, so you get a mix of good and bad red cells.
For me. this leads to the discussion of whether a drug like Luspatercept will ever be made available to thal minors once it's approved. I think it would work wonders in minors, but it may take some convincing to get doctors to prescribe it for minors.
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I tried to get a grasp on the mechanism of Luspatercept, but I'm simply not educated enough on this topic to understand it. Does it have an actual effect on MCV or MCH instead of being like EPO, which increases total hemoglobin by increasing the RBC count?
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Just having a quick read of it now. Sounds pretty groundbreaking. It specifically affects beta molecules. How interesting. Sounds like they're only testing it for severe cases where iron overload and transfusions are concerned at the moment.
Luspatercept (ACE-536) is an investigational protein therapeutic that increases red blood cell (RBC) levels by targeting molecules in the TGF-β superfamily. Acceleron and Celgene are developing luspatercept to treat anemia in patients with rare blood disorders, including β-Thalassemia and myelodysplastic syndromes .
http://www.acceleronpharma.com/products/luspatercept/
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Real basically, Luspatercept brings red blood cells to maturity that would not otherwise develop, thereby raising the Hb.
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What an age we live in. Seriously, I just love science. Fascinating, the amount of stuff we can do in this day and age.
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I believe the Hb raising property of this drug was unknown until it was tried for a different use and it raised the Hb too high in normal people to be of any use. The unexpected side effect may not have been the original intention, but will most likely be the only real use for the drug.
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Would the body recognize that the production of RBCs is now more 'efficient' and therefore slow it down, effectively decreasing hemolysis and its side effects? That would be fantastic!
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If the Hb rises, bone marrow activity decreases. Any strategy that raises Hb will have that effect. The actual stated goal of transfusion in majors is to reduce or eliminate ineffective erythropoiesis, as that is what causes many of the problems of thalassemia. Minors can use supplements like folate, wheatgrass, magnesium and L-carnitine to try to cause an increase in HbF, which would help to raise the total hemoglobin level.
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Thanks, Andy! I just thought if this drug helps RBCs to reach maturity and doesn't simply increase an ineffective erythropoiesis, would it not shift the actual ratio of functional vs. defective RBCs? I thought herein lies the difference between Luspatercept and something like EPO, because EPO would keep this original 'ratio' and therefore increase the hemoglobin levels but also hemolysis due to an increased number of defective RBCs?
I hope it's not too absurd what I wrote. :dunno
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Yes, exactly. More mature red blood cells mean less bone marrow activity, whereas EPO can only help make more of the same. The drug also reduced the iron load. From what was shown in phase 2 trials, I think most, if not all transfusing intermedias will be freed from transfusion completely by this drug and majors will see at least a 50% reduction in transfusion needs. The longer trial has a very good chance of improving on that.
I would love to it it also made available to minors with low Hb levels. It would mean such a boost in quality of life.
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Hi Andy,
I can't thank you enough for all of the excellent information you provide! After realizing that EPO didn't work for me, that Hydrea had some nasty side effects, and that testosterone worked minimally for me, but had potentially dangerous side effects, I decided to follow your nutritional advice, and feel much better than ever! I have also dialed back my training to 3 to 4 times a week, to cut down on the muscle soreness. But now you have my curiosity up with Luspatercept. I'm beta thalassemia minor with hemoglobin of around 10.5. What's your best guess regarding how long until approved? Again, folate, B 12, vitamin D, wheatgrass, organic E, L carnitine, etc, etc... are fine, but none of this can alter genetic muataions. Blessings, Phil.
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Eagerly awaiting for Luspatercept
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I think Luspatercept will be approved within a few years. Trials have gone very well for some patients, but nobody knows for certain if they got the drug or not at this point. I think a problem will arise in getting doctors to prescribe it for minor, as it may not be listed as for minors. In that case, a doctor can prescribe it in what is called off label use. I am hoping some doctors will recognize that in addition to the anemia, the ineffective erythropoiesis creates many problems for thal minors and Luspatercept has been very effective in reducing ineffective erythropoiesis. Of course, I'm using logic here, so who knows how it will play out in the real world?
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Andy,
Thanks so much for your speedy response! Your knowledge base is staggering! If it gets approval, whether or not it is prescribed for thal minor (even off label) is of little consequence to me... where there's a will, there's a way! I just want to be careful that there does not appear to be any long term, detrimental effects. Blessings, Phil