Is Pulmonary Hypertension Common in Thalassemia Minors?

Hey Moik,

PHT is not easily diagnosed and more than one test is usually employed to make the diagnosis. You can read about the various tests at http://www.mayoclinic.com/health/pulmonary-hypertension/DS00430/DSECTION=tests-and-diagnosis

I don't think EKG alone would be sufficient to make the diagnosis.

Hi Jan,

Yes, hemoglobin H is a variant, but unless you had HbH disease, where three alpha genes are deleted, you will not show this hemoglobin as an adult. It is picked up in infants at birth when they are alpha carriers, but this quickly vanishes, making a DNA analysis the only sure method for determining if you are an alpha carrier. Of course, the favism and your blood work do indicate that alpha is likely. As far as the genetics, alpha thalassemia is found in people of Mediterranean origin, even though beta thal is more commonly associated with this region. However, alpha thal is actually the more predominant thalassemia in terms of carriers worldwide.

I do want to mention that we have been hearing from more alpha thal carriers who seem to also be iron deficient. This is making me wonder about the diagnosis of iron deficiency when alpha thal is involved. There may be something that we are not yet aware of concerning alpha minors. I would suggest caution with long term iron supplementation. If long term supplements are necessary and there is suspicion that it may be the wrong treatment and is causing iron overload, a liver MRI may be advised.

Andy,

Thanks - I will definitely request the DNA testing.  I was also concerned about the possibility of iron being stored and just not showing up as serum ferritin.  In fact my serum iron is often normal.  I was in a research study that showed my hepcidin levels were high and that was my body's way of suppressing iron absorption to keep from causing more inflammation or contributing to infection.  I hate to override that whole system, especiallly since I have renal cell cancer (shrinking on its own after vitamin D therapy).  Iron can directly influence cancer growth although my hematologists/oncologists refuse to acknowledge this fact.  Here's an article on hepcidin:

http://www.pulmonaryreviews.com/feb06/hepcidin.html


I was diagnosed with pulmonary hypertension by several echocardiograms and chest x-rays.  The "gold standard" is right heart catheterization, but being so anemic the bleeding risk at this point outweighs the benefit as far as I'm concerned.  The echos were so consistent as far as the pulmonary arterial pressure that the pulmonologist doesn't have a problem with using that for proof. 

That's interesting about others with alpha thal showing up with iron deficiency.  I wonder if the inflammation from lack of NO is causing us to have a lower rate of iron absorption to attenutate an inflammatory response.  My hemolysis is extravascular...elevated indirect bilirubin, normal haptoglobin.  But it is so constant that all my red blood cell enzymes are twice the normal range so that probably means they're only 30-60 days old at the most.

Another thing that is interesting to me is that it looks like in alpha thal the red blood cells don't release oxygen as readily (s that related to 2,3-DPG levels?).  I have always felt much better at 7000-7500 feet in elevation.  Much more than that is just too much oxygen demand, but at 7000 feet the Bohr effect kicks in and causes red blood cells to release oxygen.  My doctors keep saying I should move back to a lower elevation, but I feel like I'm suoffocating when I get down to sea level.

Jan

Jan,

Bacteria, viruses and cancer cells are all proven to thrive in a high iron environment. The whole purpose of serum ferritin is to sequester iron during illness, so that it isn't available to the invader. Your body recognizes the dangers of iron, even if many doctors do not. The supplement, IP6 (phytic acid, inositol hexophosphate) has been heavily researched in regards to cancer because of its ability to inhibit the actions of iron in the cells with its antioxidant properties. This research would not take place if it wasn't already a proven fact that cancer cells thrive in a high iron environment. The world of medical knowledge is rapidly advancing and doctors who don't keep up can do a disservice to their patients. Iron is a potential poison and the body needs only a very small amount daily under normal circumstances.

You may be interested in a post at http://www.thalassemiapatientsandfriends.com/index.php?topic=1282.msg10318#msg10318
Hemoglobin level rises at high altitude to compensate for the lower oxygen concentration in the atmosphere at high altitude. This may help explain why you feel better at 7000 feet.

I don't think oxygen affinity of variant hemoglobins is related to 2,3-DPG levels, but rather is related to the structure of the various types of hemoglobin. There are over 200 known variants and some have such a high oxygen affinity, that they are useless because they don't let go of the oxygen, HbH is one of these variants and exclusion bodies are consistent with HbH. You do have several factors that suggest alpha thal trait, but with a combination of favism and parvo virus, I don't want to speculate. Parvo virus can also cause a hemolytic crisis and anemia, but this wouldn't necessarily lead to iron deficiency because the iron from destroyed red blood cells should be recycled by the body. Serum ferritin should rise along with hepcidin levels, as both reflect the body's iron regulation system. And a low ferritin coupled with normal iron can be a result of iron therapy or hypothyroid, so there are many possibilities which can lead to being treated incorrectly. Getting a proper diagnosis on the alpha thal trait could go a long way towards sorting this out. Long term iron use without any real change is reason to question the iron therapy and look for other explanations.

On the subject of heredity, I found this interesting note at http://findarticles.com/p/articles/mi_qa3890/is_200304/ai_n9219088/?tag=content;col1

Thalassemias occur in Mediterranean populations, the Middle East, parts of India and Pakistan, Southeast Asia, and Africa. However, thalassemias have also been observed in the homozygous state in persons of pure Anglo-Saxon ancestry, so ethnic origin does not preclude the diagnosis.

I think much of the confusion about which groups carry alpha thal is caused by the inability to accurately diagnose alpha trait without a DNA test. As more is learned, many assumptions are dropped. From an anecdotal point of view based on reports to this group, both alpha and beta thal trait are much more common than believed in non-malaria zones of the world, among ethnic groups not considered to be potential thal carriers. The difference in the rate of carriers between malaria zones and non-malaria zones may be somewhat explained by the fact that thalassemia carriers have had much higher survival rates during malaria epidemics, leading to a much higher concentration of thal carriers in these areas of the world. If this is part of the explanation, it becomes a matter of math and not solely based on ethnic groups. I don't think this has been considered in discussions about why thalassemia is not thought to exist among certain populations. It may have more to do malaria than any other factor. The trade off for survival in high malaria zones of the world has been a concentration of hemoglobinopathies in these areas, simply because those not carrying these defective genes have died during epidemics. Protection against malaria has been found in carriers of both alpha and beta thal, and carrier rates are as high as 75% in some areas where malaria has long been epidemic. With most of Europe not being malaria zones, the percentage of alpha carriers is only around 4% (http://emedicine.medscape.com/article/206397-overview). I'm sure a mathematical progression could be developed that would show and predict the changes in percentage of thal carriers over thousands of years of malaria epidemics, that would show how a single digit percent of carriers could eventually become a majority of the population, as non-carriers perished in epidemic after epidemic.

There is a complete explanation of lab testing for alpha thalassemia at http://www.aruplab.com/Testing-Information/resources/TechnicalBulletins/Alpha%20Thalassemia%20HBA1%20and%20HBA2%20Common%20Gene%20Deletions.pdf
This may help your doctor understand which specific test to order.

Andy,

Thanks so miuch for the references.  I'm trying not to get my hopes up too much since I know my chances of having alpha thal and HgH in particular would be so slim, but it would certainly help solve a lifelong mystery!  I have three other genetic diseases which muddied the water for so long, but I think we are finally accounting for all the strange symptoms that can be attributed to each and the hemolytic anemia is the last one to be confirmed with an actual name.  

I did a search on alpha thal in Britain and came across an older paper by Dr. Douglas Higgs:
http://www.ncbi.nlm.nih.gov/pubmed/2986751
I emailed him to see if they have any kind of registry with updated statistics on specific mutations associated with the British.  

I'm glad to hear you feel the same way about iron therapy...I have had really good results taking a powdered beef liver extract every day (with wheat grass).  My hemoglobin went from 7 to 12 in 5 months and stayed there until I got RSV pneumonia that was very prevalent here in both adults and children in March.  That started the whole hemolytic cascade again and the parvo reactivated.  I contracted the Parvo Virus B19 a few years ago from a transfusion which really was necessary to save my life, but what a crummy virus to get when you already have hemolysis!   In the UK they screen donor blood for parvo, but not in the US. My immunologist specializes in treating chronic parvo that tends to take up residence in the bone marrow in some people and he wants to do IVIG therapy, but just like iron IVs, I'm nervous about a hemolytic reaction from the increased oxidative stress.

I have been taking IP6 because it suppresses angiogenesis which helps with cancer and the proliferation of cells in pulmonary hypertension.  That, vitamin D and the pycnogenol are the primary treatments I'm using and they're working well. I had come across this study on pycnogenol that might interest you related to its effects on PH and NO production:
http://www.ncbi.nlm.nih.gov/pubmed/2986751

Jan

Interestin. Need to read a few more times though.

I just watched a great video presentation on pulmonary hypertension and thalassemia.  Even my pulmonologist who is supposed to be one of the best in the country has no clue about this. 

Here's a link to the interview with Dr. Claudia Morris and some information on a clinical trial:
http://www.thalassemia.org/index.php?option=com_content&view=article&id=243:pulmonary-hypertension-in-thalassemia&catid=1:latest-news

On the right under her picture is a link to a video presentation from last October's Cooley's Anemia Foundation Symposium:
http://www.thalassemia.org/index.php?option=com_content&view=article&id=250:videos-from-9th-cooleys-anemia-symposium&catid=1:latest-news

This is really exciting to me since no one has been able to figure out why I developed pulmonary hypertension.  The main drugs used to treat it, including Sildenafil (which is the drug used in Viagra), are contraindicated for me because of another genetic condition.  My cardiologist suggested trying L-Arginine to increase nitric oxide levels, but I didn't do well with that - it raises insulin levels and caused hypoglycemia for me.  But I found that L-Citrulline which is another amino acid related to nitric oxide synthesis doesn't affect me adversely.  It has made a huge difference in my heart and pulmonary functon.  I'm only taking 200 mg a day - that's not even a full capsule.  If I take more my vessels are too relaxed and my blood pressure drops.  Even at that low of a dose my BP went from an average of 110/70 to 80/60.  I was sleeping all the time so I divided it into two doses a day and am doing fine.

Jan

I was at that lecture. At first, I wondered why a non-specialist was giving the talk, but her talk was excellent and I hope all the thal specialists there were paying attention, because as thals are now growing older, pulmonary hypertension is becoming a big issue and its prevention and treatment are key quality of life issues, as well as a matter of survival. PHT kills and if it can be prevented and/or treated, thals will survive to even older ages, perhaps even approaching a normal lifespan, as long as the other components of their treatment programs are followed. There are many causes of PHT in thals, as mentioned in this presentation, but in the end, depletion of nitric oxide levels are at the center of PHT. I also think we need to pay attention to the findings of PHT in many children. This is something that needs to be addressed from young age and supplements can be a part of the strategy to prevent PHT. The mention of finding less PHT in patients who used hydroxyurea was also interesting and I would like to know if L-carntine supplementation was common in this group, or if hydroxyurea is a preventative on its own. I suspect it is because it does slow down the production of bad red blood cells, which does mean less hemolysis, which is one of the primary causes of PHT in thals.

Finding what works for you to restore nitric oxide levels can be a trial an error experiment, as what Jan has experienced and different supplements may need to be tried to find what is suitable for each patient, but in the end, this effort is very important, so I encourage all to pay attention. I have long suspected that it is not only thal intermedias and majors who have PHT, but from the symptoms regularly mentioned by thal minors, it is also minors who may be affected by PHT. I would love to see a broad study of this in older thal minors. My suspicion is that minors do often experience PHT, but not with the same severity as intermedias, and even though it may not threaten the lives of minors, it does cause real quality of life issues among minors. I have no scientific evidence to support this assertion, but since no studies have been done, I cannot discount the possibility of widespread PHT in thal minors, especially as they age, and especially since they often describe the symptoms of PHT as their own symptoms. I really think all thals from minor to major can benefit by increasing nitric oxide levels. L-carntinie, L-arginine, L-Citrulline are all supplements that can be tried.

I would love to hear from any thal minor diagnosed with even mild PHT. I brought this issue up with Dr Wood at Singapore and he did seem intrigued by the possibility, so I do not feel like this is just some wild guess. I do believe that minors do often exhibit symptoms of many of the ills that befall majors, but to a lesser degree, and this does need to be investigated.

Crazy year . . .

First diagnosed with aortic aneurysms, then told that I have HHT (Osler-Weber-Rendu), scheduled to have my 7+ PAVMS (Pulmonary arteriovenous malformations) embolized -still trying to confirm the CAVM (cerebral AVM) that showed up on the dynamic MRI - however, just before the embolization, bubble echo ordered . . . and PHT detected. Now it's time for the heart cath. and a million other things to address =(

I actually found this discussion board because I, like you, was interested in the implications of connecting the two.

Thank you for your time.

Ohh -- and I do have TM.

I am sorry to hear about this, but wish you luck. Please keep updating and welcome to the site

Manal

Im curious about this...even though 10 years ago I had an echocardiograpm and ekg's

Some morning I quickly run out of breath.. and need to lean on stuff

But it can go away and I even run around the block with the dogs and quickly and easily gain my breath when I get back home

It seems like this is only some days and its always in the morning

Happend a few days ago and what I tried was getting on the exercise bike and even though at first I thought I would fall over..it eventually lead to me getting over it for the rest of the day

*shrug

PHT is often associated with HHT, so it would be difficult to isolate thal minor as a contributor, but since there are many causes of PHT, it is still possible that both conditions are contributors.

A 2008 study supported the use of embolisation to treat PAVM's. http://www.ncbi.nlm.nih.gov/pubmed/18385173

Eur Respir J. 2008 Jul;32(1):162-9. Epub 2008 Apr 2.
Embolisation of pulmonary arteriovenous malformations: no consistent effect on pulmonary artery pressure.

Shovlin CL, Tighe HC, Davies RJ, Gibbs JS, Jackson JE.

NHLI Cardiovascular Sciences Unit, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK. c.shovlin@imperial.ac.uk

Comment in:

    * Eur Respir J. 2008 Jul;32(1):15-6.

Abstract

Increasing evidence supports the use of embolisation to treat pulmonary arteriovenous malformations (AVMs). Most pulmonary AVM patients have hereditary haemorrhagic telangiectasia (HHT), a condition that may be associated with pulmonary hypertension. The current authors tested whether pulmonary AVM embolisation increases pulmonary artery pressure (P(pa)) in patients without baseline severe pulmonary hypertension. P(pa) was measured at the time of pulmonary AVM embolisation in 143 individuals, 131 (92%) of whom had underlying HHT. Angiography/embolisation was not performed in four individuals with severe pulmonary hypertension, whose systemic arterial oxygen saturation exceeded levels usually associated with dyspnoea in pulmonary AVM patients. In 143 patients undergoing pulmonary AVM embolisation, P(pa) was significantly correlated with age, with the most significant increase occurring in the upper quartile (aged >58 yrs). In 43 patients with repeated measurements, there was no significant increase in P(pa) as a result of embolisation. In half, embolisation led to a fall in P(pa). The maximum rise in mean P(pa) was 8 mmHg: balloon test occlusion was performed in one of these individuals, and did not predict the subsequent rise in P(pa) following definitive embolisation of the pulmonary AVMs. In the present series of patients, which excluded those with severe pulmonary hypertension, pulmonary artery pressure was not increased significantly by pulmonary arteriovenous malformation embolisation.

PMID: 18385173 [PubMed - indexed for MEDLINE]Free Article

How are you doing now? Welcome on board.

Hi All

My 16 year old daughter has been test for pulmonary hypertension.

The tests that were proformed were echocardiogram and ultra sound of the heart.  Her tests were clear.

She is not a Thalassemia Minor.

The reason for testing was due to fainting while exercising.  She has lower blood pressure 80/40.

According to her doctor fainting while excercising can be very serious and should alway be checked out of a doctor.

Regards

Catherine

I have had a transthoracic echocardiogram (TTE), and 24 hour holter monitor  from the cardiology dept at the local hospital. except for some tachycardia during the TTE, the high heart rate i was feeling in exercising ( along with lightheadedness, nausea, dizziness, etc i was counting 180+ heart rates ) was only getting to 165bpm  while exercising - though it was just walking down nd up a hill, so to me, that seems excessive, but apparently its normal but high. I asked the cardiologist if it could be PAH but he said my thalassemia ( cos its minor) couldnt possibly be causing my symptoms.

The TTE showed no abnormal structures apparently. They were also looking to see if i had an arrhythmia or left ventricular failure, neither which turned up.

So apparently i just have a naturally high heart rate. Im also one of those people that cant tolerate humid/hot places and gets lightheaded and faint.

That said, i have a slightly high BP of around 135/88 to around 145/110. Not worth the docs doing anything about. And i had pulmonary tests done to see if i actually had asthma ( or the allergy clinic got it wrong) and the ventolin didn't make a difference.

Symptoms aren't occurring as severely now thats its not summer here in Sydney, Aus.... so *shrugs*

PAH would account for a lot of my symptoms, so I'm not sure how thorough the Cardiologist was to actually rule it out, but i got the impression he thought i was wasting his time. The registrar just told me cut out caffeine etc.