My new born baby has possible Thal major

Dear Meena,

Your doctor's are confusing genotype matching with HLA matching for a transplant.  Genotype matching is genetically determining what type of blood is genetically best matched for you so that cross matching blood for transfusion become easier and more accurate.  I am working on posting more information about this procedure - there are certain labs in the US that do the test.   For my son, the test was done in Calgary and then sent to Toronto for the testing. 

Sharmin

Sharmin,i know you explained this million of times but again ,
genotyping : is looking in the DNA for your own antigenes in order to know them and therefore choose the suitable blood for these antigens so that no antibodies are formed, right ??

So in cross matching, what are we looking for?? How does it differ from the phenotyping?
manal

Hi Manal,

I can understand the confusion surrounding these tests.  I also don't know if I am doing a good job describing it therefore I will try to post some links and will probably need some input from Andy. 

Cross match - is determining the recipients blood group and Rh.  If rbc antibodies are present then the donor blood is tested against the recipient's plasma - if antibodies are present against the donors blood then agglutination will occur and the donor blood will not be a match.  This way several donors are tested against the recipients blood until a match is found (when no agglutination occurs).

Phenotype testing - testing of the recipient's red blood cells (remember red blood cells have no nucleus and no dna) to look for markers on the red blood cells.  This is best done before a patient has been transfused because once a thal major begins transfusing 2 things prevent phenotype testing 1) the marrow is suppressed and very few retics (hosts own rbcs are produced) 2) donor rbcs are present in the recipient's blood stream.  For these reason's the patient's phenotype cannot be accurately determined.  If done before transfusions start, the patient's phenotype can be known. 

Genotype testing - uses nucleated cells (those containing patient's dna) from the serum - to determine exactly what antigen's a patient has.  This is the most sophisticated and accurate method of matching donor/recipient blood.  Once a patient's genotype is known, donor blood that contains the same antigens as the patient is safe to use and blood that contains antigens that the patient does not have can be avoided.  This way the recipient is not exposed to antigens that he/she does not have - and is less likely to become alloimmunized against it (will not produce allo antibodies against it (allo against foreign blood.) constant exposure to these antigens and formation of allo antibodies can result in auto antibodies.) 

Remember the difference between genotype and phenotype.  You may have the genotype for green eyes and for brown eyes - but you may have brown eyes.    Therefore your genotype is green & brown, but your phenotype is brown.  Genotype is all of the genes that you have, whereas  Phenotype is what is expressed (what you actually see).  For this reason the genotype gives more information then the phenotype.  For example, your phenotype for blood may be A + -- however your genotype may be O+ A-, or  A+ O- or it can be A+, A+.  For more examples see below:

Phenotype   Genotype A                     AA or A0 B                     BB or B0 AB                     AB 0                     00

I hope that this makes some sense.  I will try to find articles that explain this better than I can.  Part of the confusion is probably the fact that I am so wordy - my bad 

Sharmin

All I can add is that to put it simply, genotype tells who the real person is, while phenotype tells you who that person and every person who they ever got blood from, is.

Matching the genotype is even more important when the recipient is likely from a different ethnic group than most people in that geographic area. For example, blood donated by Americans of European backgrounds may not be a good match for someone of Asian background, regardless of a phenotype match, so genotyping the blood becomes even more important. It has been recommended that local blood banks make efforts to ensure that they have a range of blood available to match all local ethnic groups for those who will require regular transfusions. It may seem like more trouble but by minimizing or possibly eliminating antibody reactions, the patients ultimately need less blood, so it is worth it to the blood banks to have genotype matching done.

Thanks Andy
Thank you so much Sharmin, it is really clear now

But one last question, do blood banks generally do such tests on the blood packs they have or it is just enough for thm to have the blood group and the RH?? I mean if i am the recipent and i have my genotype result, is it a must to have the same test done on the blood packs found in the bank or it is enough to only have mine??

What is the protocol? To m knowlegde, banks screen donors' blood for infectios and diseases and examine the blood type and the RH only

manal

Manal,

A crossmatch is always done because factors other than blood group and rh need to be known.  If any antibodies are present in the patient blood - donor blood is added to sample of patient blood to see if reaction (agglutination) occurs (this is an oversimplification.)  The genotype information takes some of the guess work out of finding a match.  Certain donors are avoided because they have antigens that the recipient does not have.  Blood banks also save time because if the donor and recipient both have certain antigens - then the blood bank does not have to avoid them or test for them. 

I guess a simpler answer would be an extensive cross match is still done after a good genotype matching donor is found 

Sharmin

My doctor does not want to do Genotype testing. She says its not part of their usual thalassemia care. I have sent her the links from  here and argued, if that test does good to the patient why not do it. She says they will not do it, and the thalassemia team, along with another doctor is going to meet with me to answer my questions. But at the end of the day, they are not going to do the test. I am worried and surprised that they do not know about genotyping and do not want do the test being a comprehensive Thalassemia care center.  Even the Cooleysanemia.com has this pdf http://www.thalassemia.com/documents/thalhandbook2008.final.pdf which mentions about the importance of genotype testing.
What do I do.

Dear Meena,

I understand your frustration.  I am also frustrated with doctors and centers who refuse to take this simple step that can avoid possible complications in the future.  Dr. Vichinsky told us that it is very important to have this test done.  Antibodies don't always happen - and you may be safe - but if they do it can become a nightmare.  Taking this simple step can reduce your chances of producing antibodies. 

Our family has suffered a lot in the last 2 years.  This complication may have been avoided if genotype testing had been done.  I don't wish what we have gone through on anyone and for this reason I have been urging patients to get this testing done.  Unfortunately some doctors are not open to it.  The major comprehensive thalassemia care centers are doing this for all of this patients because over time they have found antibodies can pose a lot of trouble.    Antibodies can cause rapid hemolysis, iron overload, and many other problems.  To deal with them patients need to be on steroids, increased chelation, toxic drugs and sometimes removal of the spleen. 
I don't know why doctors are not open to doing the test     

The five major thalassemia centers in the world work together - Oakland, NY, Toronto, Italy and UK.  Perhaps if you can get a hold of one of these centers and have them provide more information - or have your doctor speak with them it would be helpful.  I will try to get more information for you too. 

Sharmin

Meena,

Is this at CHOP? They are one of the Comprehensive Care centers and should be following the same guidelines. Sharmin, can you ask Oakland about this?

Andy,

I will ask them. 

Sharmin

I have sent her the links from  here and argued, if that test does good to the patient why not do it.

Even though our group has hands on experience with people who face thalassemia everyday, the doctors would not take us as an authentic source. Could you instead point to the Standard Care Guideline which you mention given to us by Children's Hosptial Oakland? May be they think that is authenticated document and they know that Dr. Vichinsky's document has been written after lots of research.

This is exactly, what we like getting to know what is best and I really like Sharmin's point of not letting other's go through what they have gone through.

Narendra,

I looked through the document - it talks about genetic testing before beginning treatment but it does not talk about genotype testing for transfusions (as far as I can see - maybe someone else can find it...)  I will have to find another document.  Maybe I can them for it while I am in Oakland. 

Sharmin

Andy,
Yes this is at CHOP. That is what is worrying me even more. And during last transmission my son developed a fever, because of which they had to stop the transfusion. I hope no antibodies have already developed in his body.

Thanks
Meena

Dear Meena,

It is unlikely that he would have developed antibodies so soon.  Do you know if they did at least a phenotype test before giving him his first transfusion?   

One of the biggest risks of transfusion are transfusion reactions - which can be reduced or prevented by proper analysis of the blood before transfusion.  Phenotype testing is helpful, but genotype testing is superior.  It is helpful to know the recipient's genetic make up so that blood products can be matched properly and the patient is not introduced to anything that can cause trouble. 

Most centers do extensive cross matching - but I don't think that is enough - my son has produced many allo antibodies over the years and this would have been prevented if he were not exposed to the antigens. 

I will be going to Oakland next month - I will try to get more information and proper documents for you.  I will also bring back names and numbers of labs that do the testing.  Our doctor actually spoke with Dr. Vichinsky on the phone which was very helpful for both of them in understanding my son's case and the course of treatment. 

Most thalassemia patients visit Oakland to do SQUID testing, even when they are seen at other centers.  You can make an appointment to see Dr. Vichinsky to get an opinion.  In the future you can meet with him once a year for a follow up.  We have chosen to do this for our son.  We have been going to Oakland since he was 5 years old for the SQUID test but we never thought to see Dr. Vichinsky - this year we made an appointment with him (because Andy suggested that we do)  and we were very pleasantly surprised. 

Sharmin

Sometimes it is very much worth researching and discussing what we learn together on this site.  Andy helped point us in a direction that even the doctors in Oakland may not have thought of if we had not taken what we learned here and spoken to them about it. 

Once we presented the information that we had been discussing with Andy - the doctors agreed and proceeded with it.  By combining two techniques - his idea may have brought about a way to alleviate if not cure AIHA.  If this treatment works for little A (I am holding my breath and afraid to jinx it - but it seems to be working) - it may become a standard of treatment and help many other children dealing with the same problems. 

Never underestimate what you learn here - and never forget to ask questions if you have them.  The answer to your question could save a life. 

Sharmin