hbH Disease and hbD trait

Hi i am 28 years old man from India. I got married 4 months back. My wife (Mansi, 22)  is having HbH disease. She is Pale most of the time. her Hb is usually 8 - 9. She has not gone through blood transfusion. her billirubin is always little high (around 3) and her eyes & face is always yellowish (some times very yellow). She gets tired very easily.I had also gone through Hb electrophoresis recently and found that i have Hb D trait. Although i do not have any major symptoms i feel tired sometimes (i am suffering from hypothyroidism for last 2 years, initial stage my TSH was 20 and i felt fatigued heavily..i am on Homeopathy medicines..feeling much better now... Just thought i should mention this part). I am reading lot on internet nowadays but found no info on how an HbH disease and HbD trait couple should take their life forward?
Just to give you a little more info:
she has started taking Folic acid 5 mg tablet daily
calcium & Vit D supplement also (she is vit D deficient also as per recent test)
all as per direction of Heamatologist.

My question is - as i am new to this what are do's and dont's for us. What  are the tests we need to do before planning a baby?

Please guide us. Will be really grateful.

Thanks in Advance,
Prachit

Hi Prachit,

I found a study that addresses just what you have asked about. The results in a child who had parents with one with HbH and the other HbD was a mild phenotype, which means a thal minor phenotype (this is as I expected the study to find, since two different sets of genes are affected, so there should not be a cumulative effect).

http://rossscience.org/ojhmt/articles/2075-907X-2-3.pdf

Thus observed case conclude the co-existence of alpha 3.7 deletions with homozygous Hb D present mild clinical –hematological picture.

For both of you, I suggest a nutritious diet with a concentration on foods high in antioxidants. There should be no reason to avoid having children. They may or may not carry the thal traits from the parents, but at most a thal minor should be the result.

Hi Andy,

Thank you so much for your valuable advice.

I am sharing my and my wife's test reports for your views.

Few other test reports for Mansi , i am mentioning below:

1. Lactate Dehydrogenase     206  U/L        (Biological ref interval  81 - 234)
2. Homocysteine                   13.94 umol/l   (Biological ref range  3.7 - 13.9 micromol/L)
3. 25 Hydroxy Cholecalciferol (Vitamin D3)   9.66 ng/ml  (Reference range  for deficiency < 20 ng/ml)
4. Serum Ferritin                         37.2 ng/ml   
5. Serum Iron                             98.3 ug/dl  (range 50 - 175)
6. Total iron binding capacity        257 ug/dl     (Range 250 -450
7. % Saturation                           38.2%        (Range 14 -50)
8. TSH                                     1.762  mIU/l   (Range 0.555 - 4.7)
9. Ultrasound Abdomen & Pelvis   -  Normal Study (let me know if you require report)


Please let us know your views.

I have one more question here, doctor has suggested to do a DNA study  for Her. Is there a possibility that i may also have one of alpha gene deletion? Should i also go for DNA testing for alpha deletion?

Once again, thank you so much for all the help you are providing.

regards,
Prachit

Prachit - It is always a good idea to get DNA testing done to find out you are clear of any missing/mutated Alpha gene. Your wife's HB level seem to be low. Please make sure she eats healthy diet and takes the required vitamins.

Thanks Narendra.
i was also thinking same way. Before planning for DNA test it will be helpful to get opinions of more people.
is hb 8.5 not normal for hbH person? is it risky? how can her Hb can be increased? any suggestions

i am also lookingforward to get more views on our reports..as i can see people in this thalpal group have excellent knowledge of thalassemia. looking forward to get more opinions.
thanks

Please go through these links with reference to Hemoglobin H

http://thalassemia.com/treatment-HbH.aspx#gsc.tab=0

Treating Hemoglobin H Disease
Often the patient with hemoglobin H is asymptomatic and is unprepared for the acute complications that occur during infection, pregnancy, and drug exposure. In particular, these include hemolytic and aplastic anemic episodes. Folic acid supplements and avoidance of oxidative compounds and medications are recommended. In mild cases, biannual visits are adequate. In more severe cases, more frequent visits are indicated. At routine visits, growth, development, facial bone deformity, dental status, and hepatosplenomegaly should be monitored. Routine monitoring of hemoglobin levels is required.

Patients with hemoglobin H disorders develop neonatal anemia. Splenomegaly and hypersplenism are relatively common. Splenectomy usually ameliorates the severe anemia noted in nondeletional hemoglobin H cases. Splenectomy may be required at a very young age in transfusion-dependent cases. Prophylactic antibiotics and infection precautions are similar to other splenectomy patients. Thrombosis prevention is indicated in cases requiring splenectomy. Low-dose aspirin or other anticoagulants may be used.

Ongoing monitoring of iron stores with quantitative imaging of the liver is indicated because of the unreliability of serum ferritin tests. In nontransfused patients, imaging should be initiated in early adolescence. Cardiac function monitoring is indicated. The frequency is determined by the anemia and the iron-overload status. Gallstones frequently occur in hemoglobin H disease, and cholecystectomy is indicated in symptomatic patients. Bone-density measurement should be initiated in early adolescence. Pregnancy requires more frequent monitoring because of the risk of severe anemia and pre-eclampsia.

Reference : http://thalassemia.com/treatment-HbH-Lal.aspx#gsc.tab=0

Hemoglobin H disease (HbH) is a form of alpha thalassemia in which moderately severe anemia develops due to reduced formation of alpha globin chains. In this condition, as in the other forms of thalassemia, there is an imbalance of globin chains needed to form hemoglobin. Normally, there are four genes to produce alpha globin chains. When three out of four of these genes become inactive, there are too few alpha globin chains to combine with beta chains and give rise to normal hemoglobin (hemoglobin A). The excess beta globin chains then combine with each other to form hemoglobin H, which is the origin of the name "hemoglobin H disease."

While most individuals with HbH do not require transfusions, there is heterogeneity in the clinical course. This is an important component of the counseling for the family at the first clinic visit. HbH caused by deletion of three genes (deletional HbH) is less severe than cases in which two genes are deleted and the third gene has a point mutation (non-deletional HbH). HbH Constant Spring (HCS) is the most common form of non-deletional HbH in the United States.

In California, all newborns with HbH are identified through newborn screening, followed by identification of the alpha globin gene deletions or mutations by the Hemoglobin Reference Laboratory located at Children’s Hospital & Research Center Oakland. Older patients who are seen for the first time should have DNA testing to identify alpha globin gene deletions and the presence of the Constant Spring (CS) mutation. If only two alpha genes are deleted and the CS mutation is absent, further testing for uncommon mutations should be done. These patients should not be categorized as deletional HbH. Patients with HbH should also be screened for beta globin gene mutations with multiplex PCR. The complete genotype is used as the basis for discussion of a future clinical course and genetic counseling.

Routine Care

Patients should be seen frequently in the first year after diagnosis to establish hemoglobin level and monitor growth. Communication with the primary care provider is also important so that care can be coordinated. Later visits to a thalassemia center should occur once or twice a year, and routine health maintenance should be provided by the primary care provider. Patients with HCS should be followed closely by the thalassemia center because of the potential for severe anemia, growth delay, iron overload, and the need for splenectomy. All routine childhood vaccines should be completed and seasonal influenza vaccine given every year. All patients should receive folic acid, 0.5 to 1.0 mg per day.

Management of Fever

Owing to the risk of severe anemia during infections in HCS, such patients should be seen on the same day in the clinic or emergency room. Patients with deletional HbH can usually be seen in the clinic on the next day, unless an ER visit is warranted by the symptoms. A blood count with reticulocyte count and bilirubin level should be obtained. An admission for observation or transfusion may be needed if the hemoglobin has fallen below baseline. Antibiotic treatment is determined by assessing the source of infection. All splenectomized patients with fever should be seen on the same day and started on antibiotics (ceftriaxone is preferred). An admission is recommended until sepsis can be excluded. Oxidant drugs, which cause hemolysis in G6PD deficiency, should be avoided.

Splenectomy

Splenectomy is not required for deletional HbH disease. It may be required for patients with HCS when there are multiple episodes of sudden fall in hemoglobin level requiring transfusion, or if anemia is severe and affecting growth.

Transfusion Therapy

Common infectious diseases, such as common cold or viral fever, can lead to a rapid fall in hemoglobin level in HCS patients. The fall in hemoglobin level in HbH patients is much smaller, and the development of severe anemia needing transfusion is unlikely. Transfusions are given when hemoglobin falls below 6 g/ dL. As mentioned above, splenectomy is recommended if there is a need for frequent transfusions. There is little role for chronic transfusion therapy such as that given to individuals with beta thalassemia major.

Iron Overload
Iron overload occurs in adults with HbH. In HCS, there is early iron overload that may need treatment. Patients’ ferritin and liver iron concentration should be monitored and measured via MRI or ferritometer.

Outreach
Patients should be provided with a card that shows the diagnosis and emergency contact number for their hematology service. Clinical summaries should be sent to the primary care provider with treatment recommendations. Families should be given a letter for school to explain the need for clinic visits. Children are allowed to determine their own limits of activity during physical education with no routine restrictions.

Adults with HbH
Genetic counseling is extremely important for adults. Ideally, a full testing of an adult patient’s partner for alpha and beta thalassemia mutations should be performed. At a minimum, testing for alpha thalassemia trait should be done to determine any risk for alpha thalassemia major which can be fatal to a fetus.

Patients with HbH who become pregnant should be monitored for further drop in hemoglobin level. Most of these patients will not need transfusions. Pregnant patients with HCS need close observation and should start regular transfusions if hemoglobin drops below 7 g/ dL. Transfusions are performed every three to four weeks with the aim of maintaining pre- and post-transfusion hemoglobin levels at 9 and 12 g/dL, respectively.

All adults should have echocardiograms to screen for pulmonary hypertension, more frequently in those who are splenectomized. Older patients, particularly with HCS, should be evaluated for fatigue, difficulty in coping at work, and family stress.

Conclusions
Deletional HbH is asymptomatic during infancy and childhood, although deficits in growth may appear among older children. These individuals should receive all routine care through a primary care physician, with periodic evaluation by a hematology center. The key points are counseling the family and adopting strategies to avoid blood transfusion. In contrast, HCS is a potentially serious disease that needs close follow-up by a thalassemia specialty center to plan for emergency and elective transfusions, measure iron overload, monitor growth failure, and evaluate the need for splenectomy.

You have to make sure Mansi's HB levels are maintained and also find out if there is any Iron overload. If there is Iron overload,  chelation  (removal of excess iron) should be done. Also, as you can see Genetic Counselling is very important.

Prachit,

I also think it would be wise to verify through DNA testing that you don't carry alpha trait. This should be done as a precaution before having children.

The best thing your wife can do is take folic acid, 2-5 mg daily, 5 if pregnant, eat a good diet and avoid all chemical fumes (this may include synthetic perfumes and household items like fabric softeners). Some chemicals can cause hemolysis, dropping the hemoglobin level. Her Hb is fairly typical of HbH but folic acid might help bump it up slightly.

Thanks a ton Narendra and Andy.
@Narendra : her serrum ferritin level i have mentioned in my previous reply. it is in range.
@ Andy : just wanted to confirm whether you cud see our reports i attached in previous reply?
she is taking 5 mg folic acid daily.
one query- what shud we tell to doctor if we want to do a test to check alpha deletion? what is the name of test.?
as you know it will be very expensive just wanted to be sure before going for it.

should she be not using deodrant and normal cloth washing detergent also? sorry for silly question

Also other than folic acid what can help her to get more active and increase her Hb level.

Yes, I saw the reports.

The question is quite good actually. Avoid chemical scents. Unscented detergents are available. I already feel that many deodorants should be avoided because they contain the poison, aluminum. Heavy artificial scents should be avoided. Chemicals like moth balls are a threat. Gasoline and similar fumes can also spark hemolysis. Observation is important. If she suddenly feels weak and tired, look at what exposures she has had. Go through the list at http://www.thalassemiapatientsandfriends.com/index.php/topic,3410.msg34830.html#msg34830

Not much helps alpha thals increase Hb. A nutritious diet is essential for building red blood cells, but alpha thals cannot take advantage of substances that promote fetal hemoglobin, as this requires an excess of alpha globin to work.

You would need a DNA analysis to rule out that you are an alpha carrier. The cost should be considered in the context of the costs involved with having a child with HbH, and this cost is beyond financial.

Andy thank you for your quick replies.
Information is really useful.
what do you think about toilet cleaners (Harpick etc) dettol and other cleaning agents (phenyl) , dilute acid solution used for cleaning floor and Goodknight coils elecrical coils used for mosquitoes?
i am sorry i am asking lot many questions but these are very common things used at home and want to know whethet it is important to get rid of them?
usually she doent get hemolytic episode at home.

Doctor also suggested her Udiliv 300 tablet twice a day. cud you pls tell me why is it prescribed?

She has got acnes.does it have any connection with hbH disease? She has started homeopathy medicines for acne.

yes i agree with you, loss is beyond financial if we have any issues with baby. just wanted to sure the test is correct because awareness is low.

doctor also suggested dna test for her and not for me. but what i understand is for me to go thru DNA test is also very important.
so i am planning DNA test for both of us.
which is the best reliable place in mumbai to get this test done ? any idea?

once again i appreciate you for all the guidance you are providing.

Hi Andy,

one more doubt. will wheat grass help her? if yes how to take it?

Prachit,

Cleaners that contain perfume scents are to be avoided. Chemical fumes such as what is given off by mothballs should also be avoided.

The red blood cells of thals break down more quickly, raising bilirubin levels and raising the possibility of gallstones. Udiliv is used to try to reduce the bilirubin level.

Wheatgrass cannot raise fetal hemoglobin in alpha thals, as it requires an excess of alpha globin to do so. It may have positive qualities outside of raising Hb, but you can't expect to see the Hb rise from using wheatgrass in alpha thals.

Hi All,

Myself and Mansi went for DNA testing. We will get our reports in 20-30 days. I will post here as soon as i get those.
She is taking folic acid 5mg cirrently.
I am considering to give Mansi following supplements in addition to folic acid;
1. Ca 500 mg
2. Mg 250 mg (I am not able to find Mg suplement here in India)
3. Vit D  60000 IU she took every week for 3 months (her D level was 9). Now she has stopped it. I am planning to give her 60000 IU dosage once in 2 week. Is it ok to give high dose once in week or 2 or it is better to give 200-5000 IU daily?
4. Vit E natual (NatVe or something) 400 IU

when she should take these supplements? after meal ? can she take vit E and Ca/Mg together? Can you please give me best schedule to take these supplements?

She was having pain in legs for atleast 20 days (below the toe and below ancle). it automatically disappeared. what may be the reason for this?

As i told earlier i have hbD rait..Do i also need to take these supplements? I was vit D deficient (14) i managed to get it to 30 aftewr taking calcirol 60000 IU for 3 months ..once in a week.

Keep up the vitamin D plan as it appears to be helping. It greatly increases mineral absorption and may explain the relieving of the pain. You might find calcium and magnesium in a supplement together, as calmag is a very common supplement. I take all my supplements after a meal. It seems easier on the stomach.

Hi Andy,

Thanks for your quick reply.

Being hbD trait should i also think of taking Vit E, Ca-Mg  along with Vit D?

Are dosgaes of supplements mentioned for Mansi ok?

Here we get Calcimax forte but it contais only 100 mg Mg and 400mg Ca.

Regards
Prachit