My Dominant Hemisphere

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HLA-haplotypes and the Blood Transfusion vs. Bone Marrow/Organ Transplantation paradox

with 6 comments

Blood donation between family members should be discouraged ~ Harrison's 16 ed
Source

Explain the following dichotomy &/or paradox :-

Q. Why is it that while blood donations between family members (in other words, those individuals who share HLA-haplotypes) are discouraged, bone-marrow/organ transplantations are encouraged between them?

Background keywords :-

  • blood (a type of connective tissue) – blood relative – HLA haplotype sharing – donor lymphocyte attack on host cells – transfusion associated graft versus host disease (TAGVHD) – blood donation from family donors contraindicated unless products irradiated
  • organ donation – allogeneic bone marrow transplantation – closely matched HLA donor – family donor – host versus graft reaction or graft rejection – acute & chronic graft versus host disease (GVHD) – leukemias – graft versus leukemia effect – donor lymphocyte infusion – reduced intensity bone marrow transplantation

Apparently, GVHD is not so much of a problem in bone-marrow/organ transplantation when compared to blood transfusion. In fact, the graft versus leukemia effect (a type of GVHD), coupled with donor lymphocyte infusion, is used to our advantage in ‘reduced intensity bone marrow transplantation’ for the treatment of leukemias. Why the difference?

Background books:-

——
http://commons.wikimedia.org/wiki/Image:Apfel_05.jpg“Millions saw the apple fall, but Newton was the one who ASKED WHY.”
~ Bernard Mannes Baruch
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Copyright © Firas MR. All rights reserved.

Written by Firas MR

July 5, 2007 at 7:57 pm

6 Responses

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  1. If this a question in search of an answer i’d be happy to share, but i can’t tell from the format.

    PalMD

    July 5, 2007 at 8:16 pm

  2. Hello! You are welcome to share! :)

    Firas MR

    July 5, 2007 at 8:21 pm

  3. Blood typing is rather simple…usually. Family members are not excluded…UNLESS you may need a bone marrow/stem cell transplant for whatever reason. Most people who need transfusions can simply be ABO typed. There are a few exceptions.

    As stated above, organ and bone marrow/stem cell transplants are VERY different. Also, it depends on what the transplant is for.

    Organ transplants must be matched for certain things, and anti-rejection drugs are almost always needed anyway.

    Bone marrow/stem cell txplants can be used for various reasons, and can come from the patient themselves, or from a donor. Obviously, the patient is always a perfect match for themselves. Also, close family members are more likely to match then strangers. After that, members of the same ethnic group can be screened.

    The idea behind marrow transplants for cancer can be fairly simple…the thing that prevents us from using REALLY high doses of chemo and radiation is that it kills the bone marrow…so if we plan a donation, we can kill away…making killing cancer cells more likely. Then marrow (these days, stem cells) can be re-infused so that the patient doesn’t die of marrow failure.

    The white cells in the patients body can detect new organs and try to fight them off as invaders…a nasty problem of rejection.

    In marrow transplants from a donor other than the patient, the white cells from the DONOR attack the patient…yucky graft-versus-host disease. This effect, if managed properly can also help fight the cancer, however, as the foreign white cells kill off the patient’s cancer cells.

    I’ve probably made a godawflul mess of this, but i hope it helps.

    PalMD

    July 5, 2007 at 9:51 pm

  4. Hi again! And thank you for your input. It really is appreciated. :-)

    To reiterate, the question calls for the explanation of an interesting paradox: when it comes to HLA-identical individuals, blood transfusions are contraindicated/discouraged (due to the rare but ‘always’ fatal complication of TAGVHD; and yes, Harrison’s 16 ed says so too). This is in contrast to bone marrow/organ transplants, where, having an HLA-identical donor, is in fact a good thing.

    Blood is just as much of a tissue as any other organ in our bodies. So how do you explain this dichotomy? Can you provide a more specific and/or articulate answer? Thank you, once again!

    Here’s an excerpt from Harrison’s 16 ed, that explicitly states that blood donations among family members should be discouraged:-

    “…Directed donations by family members should be discouraged (they are not less likely to transmit infection); lacking other options, the blood products from family members should always be irradiated…”

    Source: Harrison’s Internal Medicine > Part 5. Oncology and Hematology > Section 2. Hematopoietic Disorders > Ch 99 Transfusion Biology & Therapy

    Firas MR

    July 6, 2007 at 3:53 am

  5. well,…heres an incomplete answer to ur query…..

    As you have already pointed out blood transfusion among relatives is associated with the rare complication of TA GVHD.

    TA GVHD is caused due to the DONOR lymphocytes recognising the recipients tissues as foriegn and destroying them.

    Here are 3 scenarios….

    1)Immunocompetent HLA nonidentical recipient:
    The Recipient will recognise the donor lymphocytes as foriegn and destroy them.
    Thus no lymphocytes will be left to start a GVHD

    2)Immunodeficient HLA nonidentical recipent:
    This host will not be able to kill the donor lymphocytes even though they are recognised as foriegn…resulting in an increased prevalence of TA GVHD among immunocompromised people..

    now coming to the main topic….
    3)HLA identical immunocompetent recipient…
    The recipient will NOT be able to recognise the donor lymphocytes as foriegn because they are HLA identical!!
    so,,,they survive….engraft….and elicit a TA GVHD.

    Im still searching for an answer to the 2nd part of ur question….!!

    ANIRUDH....

    July 11, 2007 at 5:49 pm

  6. Hi Anirudh!

    Thanks for your insights. I do see your line of thinking and have to say it makes sense, albeit limited to the context of blood transfusions. What is baffling is the paradox, and that still begs an answer! Logically, I suppose we might be overlooking an important difference between blood as a tissue and other organs.

    Or is it that we do not prescribe transfusions between relatives for the mere fact that TAGVHD has statistically been found to be ‘always’ fatal in contrast to GVHD problems associated with organ transplants, where that might not be the case? Is our approach purely borne out of statistics alone and nothing else? :-P It is worth noting by the way, that medics are quite apt at conveniently filling gaps in their knowledge using statistics!! I understand that statistics don’t lie, and at least, at an empirical level choosing such a strategy to understand this works, but what CAUSES this statistical difference to occur in the first place? What is the underlying pathophysiology that orchestrates this paradox? That’s the million dollar question! :)

    Firas MR

    July 11, 2007 at 8:27 pm


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