Slow rate transfusion and warm antibody

Andy,

Thank god for you!
I talked to my son's doctor 2 weeks ago - and we did the transfusion at a very slow rate.  He was also hit with a big dose of prednisone.

Last time his hg after 2 weeks was 80.
Today, his hg after two weeks is 122.
His doctor asked us to come back in another 2 weeks. 

He is looking great - his lips are as red as cherries and he is very upbeat and he has been playing with a ball
for hours like a puppy.   
 
Thank you for your advise, we will continue to transfuse him at a very slow rate. 
What a scare he gave us 2 weeks ago! 

I hope your daughter is doing well Andy.  I am happy about her nursing internship - she must be so happy. 

Sharmin 

Sharmin,

This is wonderful news and I hope the high dose of prednisone can eliminate the problem. It has been stubborn but these antibody issues can correct with aggressive prednisone use. Let's hope the slower rate will lessen the reaction. It does seem like it would be less shock to the system this way.

My daughter is still feeling tired but with her workload anyone would be. Her physical is in May after school ends. She is now confirmed for the nursing internship for 8 weeks this summer. She will be working in the ICU at the local community hospital in Buffalo, and getting paid rather well. She's excited.

Congratulations Sharmin, i am so happy for the good news

Andy, i wish your daughter all the luck in her summer internship   and please keep us updated about her tests

manal

Good to hear that Sharmin

Andy,

Wishing your daughter, the best of luck for her career!

Hi everyone,
my son did great for about 3 weeks after his last transfusion.  This week his lips seem a little more pale and he is suddenly lethargic.  He has never fallen asleep during the day - but today he fell asleep as soon as he got home from school - and has been feeling unwell all day and he has an upset stomach.  Just when I think things are getting better  .

Andy, he was on a very high dose of prednisone this time - usually such a dose could get him through 5 weeks.  This time - if his hg is low - it has only gotten through 3 weeks - could this mean that the prednisone is not working as well to control the antibody?  I am quite anxious, if the prednisone can't control the antibody then what will happen 

Sharmin,

I wish there was something definite I could tell you, but with antibody reactions, it is often the case that there is no easy answer. Different tactics are tried and maybe a combination of tactics may work. Taking less blood at a slower rate is one. Prednisone is another. I have read that sometimes EPO is used along with prednisone but with mixed results. Although this is troubling, it can't be considered severe hemolysis, as his transfusion frequency is still measured in weeks. In cases of severe hemolysis, the initial dose of prednisone can be 100-200 mg.

http://www.merck.com/mmpe/sec11/ch131/ch131b.html

Corticosteroids (eg,  prednisone Some Trade Names
DELTASONE
Click for Drug Monograph
1 mg/kg po bid) are the treatment of choice in warm antibody idiopathic AIHA. In very severe hemolysis, an initial loading dose of 100 to 200 mg is recommended. Most patients have an excellent response, which in about 1⁄3 is sustained after 12 to 20 wk of therapy. When stable RBC values are achieved, corticosteroids are tapered slowly.

I have mentioned this before and wonder if it is practical to find donors who are better phenotype matches. Donors with a similar ethnic background may help minimize the compatibility problem.

http://www.ncbi.nlm.nih.gov/pubmed/11071629

The effect of red blood cell (RBC) phenotypic differences between donors (mostly white) and Asian recipients on the frequency of alloimmunization was determined. Additional transfusion and patient immune factors were examined. 14 (22%) of 64 patients (75% Asian) became alloimmunized. A mismatched RBC phenotype between the white population, comprising the majority of the donor pool, and that of the Asian recipients, was found for K, c, S, and Fyb antigens, which accounts for 38% of the alloantibodies among Asian patients...Transfusion of phenotypically matched blood for the Rh and Kell (leukodepleted in 92%) systems compared to blood phenotypically matched for the standard ABO-D system (leukodepleted in 60%) proved to be effective in preventing alloimmunization (2.8% vs 33%; P =.0005). Alloimmunization and autoimmunization are common, serious complications in Asian thalassemia patients, who are affected by donor-recipient RBC antigen mismatch and immunological factors.

http://www.blackwell-synergy.com/doi/abs/10.1046/j.0041-1132.2003.00589.x

RBC autoimmunization and the development of autoimmune hemolytic anemia should be recognized as a complication of allogeneic blood transfusion. The need for additional blood transfusion was successfully avoided in one patient by treatment with recombinant human EPO and corticosteroid therapy. Once RBC autoimmunization is identified, subsequent management should incorporate a strategy that minimizes subsequent exposure to allogeneic blood.

http://bloodjournal.hematologylibrary.org/cgi/content/full/97/12/3999

Previous data on a presumed homogenous population in Greece and Italy also showed an overall low rate (5% to 10%) of alloimmunization.2-3 The difference between our experience of lower rate of alloimmunization (7.4%) and Singer et al's higher rate (22%) can be explained by our access to phenotypically matched donors in Hong Kong. We agree with Singer et al's recommendation that the recruitment of Asian blood donors in North America, just like the recruitment of black donors for sickle cell disease patients, can increase the availability of compatible blood for thalassemia patients, who have a lifelong need for transfusions.

If there is a large enough Asian community in your area, it may be practical to arrange for blood from a similar population. It may require some work to find a group of matching donors or it may be possible through the blood bank. It is something you should talk to the doctor about. I would also suggest that if it is at all possible, you consult with Dr Vichinsky about this. I don't know if a phone consultation would be possible, but it would seem sufficient as an examination of your son shouldn't be necessary. Dr Vichinsky has much experience with this and may be able to advise a strategy to deal with it before it does become worse.

Thank you Andy.  We plan to see Dr. Vichinsky in the fall - I wonder if perhaps we should go sooner. 
After his nap - he bounced out of bed and seems well.  His color also looked a little better. 

The highest dose of prednisone he has been on is 40mg - for 7 days.  It was then tapered to 20 (4 days), 10 (4 days) and now we are on 10mg every second day as usual.  His rate of transfusion was decreased from 90cc/hr to 80cc/hr - but he was given both units.  Next time perhaps we can slow the rate further and take only half the amount - and go in two weeks later for the other half.  I think this may be best in the long run.

My son's blood type is O - and he has 7 allo antibodies so it is really difficult to find a donor for him.  The hospital takes 4 large vials of blood to cross match him. 

We will make an appointment to see Dr. Vichinsky as soon as possible - thanks again Andy. 

We'll do his blood test Thursday morning - if his hg is still in the 90s (it will be almost 4 weeks) then things are good.  I'll keep you posted.

Thank you for all of the information - I will share it with our doctor.
S

Andy,

My son's hg today is 80 - 3 weeks post transfusion.  I am really confused because 1 week ago it was 122.  He looked great until last Friday - very red - but he woke up looking pale Saturday morning.  I know that most of the hemoloysis happened over night.  I am not sure what would have caused the sudden drop.   I was hoping that he would be at least 90 because of the high dose of prednisone he was on.  I am hoping that we can begin transfusing him at a slow rate every two weeks, because I notice that it is between the 2nd and 3rd week that he drops drastically.  I wonder if transfusing him 15cc/kilo rather than the 20cc/kilo he is getting now - every two weeks may be best.  I know that the transfusion requirement is not out of control right now, but the problem is getting worse rather than better. 

I am very afraid right now, and we are looking into seeing dr. vichinsky next month. 

Thanks again,
Sharmin

Sharmin, i am praying for you and for your son. I am sure that things will be much better, please update us
manal

Manal,

Thank you so much for your support.  The hospital called saying that they will need more time to find matching blood for him - I hope that they find it soon, before the antibody reduces his hg further.  Our pediatrician says that Andy's suggestion makes a lot of sense and wants to follow the plan that we suggested to him.  It has been a stressful day waiting around for the blood, but my son is running around playing so that makes me feel better.  His eyes are bright and he looks very happy.  We have to be thankful for every positive moment we get:)  Thank you for your prayers Manal, I pray that all of our children are healthy soon.   

Give lots of hugs and kisses to Maani from his aunt Zaini 

I hope everything will be alright with this handsome young man

ZAINI.

Thank you Zaini 
I love you Manal and Zaini - what would I do without you??

We are still waiting for the blood bank to find blood.  I'm sure they will find it either later today or tomorrow morning. 
I'll let you know when they do:)
 

Sharmin

Sharmin,

The slower transfusion rate with less blood should make some difference.

http://www.clinlabnavigator.com/transfusion/WarmAutoimmuneHemolyticAnemia.html

A critical aspect of transfusing patients with AIHA is to avoid over- transfusion. The kinetics of red cell destruction always describe an exponential decay curve, indicating that the number of cells removed during a unit of time is a percentage of the number of cells present at the start of this time interval. Raising the hemoglobin level abruptly is likely to increase the amount of hemolysis that is occurring and may precipitate DIC. Indeed, the most common cause of post transfusion hemoglobinemia and hemoglobinuria in AIHA may not be alloantibody induced hemolysis but rather the quantitative effect of increasing the red cell mass subjected to ongoing autoantibody hemolysis. Accordingly, transfusion of comparatively small volumes of blood is the optimal means of minimizing the danger of transfusion-induced intravascular hemolysis. The patient's hemoglobin level should be maintained just above a tolerable level until more specific therapy becomes effective.[/size]

 I've been reading about blood matching which has been done using phenotyping. In recent years, it has been shown that genotype matching of blood can give a more accurate match.

http://www3.interscience.wiley.com/journal/98518982/abstract?CRETRY=1&SRETRY=0

Genotyping was very important in determining the true blood groups of many polytransfused patients with -thalassemia, and it assisted in the identification of suspected alloantibodies and the selection of antigen-negative RBCs for transfusion.

By using this along with phenotyping, a better match is found. After many transfusions, it becomes difficult to determine the true blood type because so many foreign antibodies have been introduced via transfusions. Genotyping matches for the true blood type.

http://cat.inist.fr/?aModele=afficheN&cpsidt=1466407

After multiple transfusions, the serologic typing of autologous blood group phenotypes is difficult, because of mixed RBC populations. The genotyping of ABO, Rh, Kell, Kidd, and Duffy systems could be used to determine autologous blood group antigen status...Genotyping from peripheral blood produced results identical to the autologous blood group phenotypes, regardless of the amount of blood transfused or of the length of the sampling period after transfusion. CONCLUSION: A fast and reliable PCR.sequence-specific primer DNA genotyping assay for simultaneous determination of autologous ABO, Rh, Kell, Kidd, and Duffy blood groups can be performed on peripheral blood samples, even though the patients have recently received multiple transfusions.

http://cat.inist.fr/?aModele=afficheN&cpsidt=18300371

The development of red blood cell (RBC) isoimmunization with alloantibodies and autoantibodies complicate transfusion therapy in multiply transfused thalassemia patients...In conclusion, the transfusion of matched blood is essential for chronically multiply transfused patients in order to avoid alloimmunization. Considering the high frequency of anti E at our hospital, it is advisable to genotype patients and match the red cells for E antigens in multiply transfused thalassemia patients.

I do not know where the current state of genotyping is or if it is even being done on a routine basis. There is a movement in Europe to replace the old method of phenotype with DNA genotype. There is a group called Bloodgen that is working to make genotyping the standard for blood matching.

http://science.uwe.ac.uk/projectshowcase/neil_avent.asp

Bloodgen is an international consortium led by Professor Neil Avent and colleagues in FAS. The consortium aims to use genotyping to improve patient safety and blood transfusion compatibility.

In most developed countries safe blood transfusion is taken for granted. But, not all blood groups are compatible, and blood grouping is complex, with two cross-matching tests required prior to transfusion.

What's more, these tests are based on technology that has not changed since the early days of blood transfusions. Bloodgen aims to change all that with the development of a 'Bloodchip' - a CE-marked commercial product that will be sold to Blood Services worldwide.

There are 29 different blood group systems but currently only ABO and Rh (Rhesus) are routinely tested for. Professor Avent, Director of UWE's Centre for Research in Biomedicine and leader of the project said:

"Inevitably there is going to be some incompatability with blood transfusions, especially in those that receive multiple transfusions, because if it is incompatible the patients' immune system will create an antibody. Blood grouping at the moment uses antibodies that interact with proteins on the surface of cells.Our research looks at blood group specific genes which vary from one individual to another. This is certainly a safer means of testing blood because of its comprehensiveness. The Bloodchip will embrace all blood groups that are clinically significant and we'll be able to have those tested on a routine basis."

"The ultimate goal is that a new technology will come in and replace techniques that have been around for 100 years or so. Genotyping is incredibly accurate and could be used for a wide range of routine testing of patients in the near future."

The Bloodgen consortium, which is supported by a large EC Framework V grant, pulls together expertise from around the globe. The partners are: Biotest AG Dreieich, Germany; Bloodbank, Rotterdam; Blood Group Reference Centre, Barcelona; Institute of Haematology and Blood Transfusion, Prague; the North Bristol NHS Trust, Southmead, Bristol; Progenika SA, Spain; Sanquin Research Foundation, Amsterdam; University Hospital, Lund; University of Ulm, and the University of the West of England, Bristol (lead partner).

Genotyping will eventually replace phenotype matching of blood. One article I read from 1999 talked about the white population having been genotyped but others, such as Asian still needed to be done. I don't know how much progress has been made in the past nine years but I think this is an important subject to bring up when you speak with Dr Vichinsky.

I read until I couldn't keep my eyes open the past two nights, trying to find information for you and Rozitka about antibody reactions. It is somewhat frustrating because it is a very difficult problem that affects a percentage of those receiving blood transfusions and there are no easy answers. I hope each little bit of knowledge can come together to help in some way.

Andy,
I can't thank you enough!  This is so much useful information - and I can see the pattern - when our doctor began transfusing him more aggressively - the antibody only became more active.  I will take all of this information to him so that we can find the optimal method of treating him.  Thank you from the bottom of my heart 

I'll keep you posted,

Sharmin

Sharmin,

I have worked so hard at trying to find answers and it makes it all worth it to know that anything I found can be of even the smallest help. I am also really happy that your doctor is willing to look at these things and use what he thinks may help. I never am trying to show doctors up and really hope that my contributions can be seen as what they are, and that is sincere attempts to give some information that can help. I realize that with the amount of work many doctors are confronted with, that they may not have the time available to do the hunting that I can do. (And believe me, no one wants their doctor to be as bleary eyed as me after a couple nights reading medical study summaries).  I hope any doctor can find some answers in the information I compile. Your doctor has been so open to the information I dig up. I hope all doctors can understand that we're all trying to do the same thing and that is help patients. We hear a lot of negative comments directed towards doctors and much of this is the result of doctors just not having prior experience with thalassemia. I don't think any doctor should be criticized for this, but the criticism may begin when a doctor is confronted with thal and makes no attempt to further his/her understanding. I feel this is a minority of doctors who are like this and I think if patients encourage their doctors to find correct information, that we will see far fewer complaints, as most doctors do take their work seriously and will try to learn what they can if they know the information they possess is not complete. Sharmin, your doctor is doing a great job and has shown so much willingness to look at information that may help make life better for your son. I hope a solution to this autoantibody problem is forthcoming.