Understanding 'Rh-disease'
Sunday, February 18, 2007
Kenneth F. Trofatter, Jr., MD, PhD
The immune system has various methods of destroying invaders and we will not go into detail regarding these pathways today. However, in the case of Rh-sensitization, the fetal RBCs are predominantly destroyed by cells that attack, nonspecifically, whatever antibody has attached to. Most of the destruction of Rh-sensitized fetal RBCs occurs by cells, such as macrophages, comprising what is termed the ‘reticuloendothelial (RE) system’ that is highly concentrated in organs such as the liver and spleen. Fortunately, these cells are not capable of mounting a permanent immune response to these antibody-sensitized fetal RBCs, which is a GOOD thing for the baby. (In other words, after birth, once the mother’s Rh-antibodies are eliminated, the baby will no longer attack its own RBCs, although the destruction can continue after birth until such time as the antibodies are gone). There are several consequences of the RE system’s response that contribute to the course and physical changes associated with what we then term ‘Rh-disease’ in the fetus.
First, the RE system begins to break down the fetal RBCs at a faster rate than RBCs usually turn over. RBCs contain the hemoglobin that is necessary for carrying oxygen throughout the body. When RBC destruction exceeds the ability of the baby to make sufficient quantities of new RBCs to keep up with the needs of the growing fetus, then anemia begins to develop. As the baby grows its need for more RBCs increases rapidly; and, as the placenta develops throughout gestation, it becomes more efficient at transferring maternal antibodies (including anti-Rh antibodies) to the baby. Unfortunately, in the case of Rh-disease, this accelerates the destruction of fetal RBCs. This combination of events places the baby at greater risk for severe anemia as the pregnancy progresses.
In addition to the destruction of fetal RBCs, the primary organs in which this occurs, the liver and spleen, also begin to enlarge. This enlargement is the consequence of several factors. First, the cells of the RE system proliferate (to some extent) and enlarge as the result of destruction and consumption of the fetal RBCs. Secondly, while the baby is in the womb, the liver, in particular, and the spleen are important sites for the production of fetal RBCs, an event that usually shifts more to the bone marrow as pregnancy progresses. As the baby becomes anemic, the production of RBCs in these organs (called extramedullary hematopoiesis) actually accelerates, rather than diminishes, and the proliferation of precursor cells responsible for the production of new RBCs contributes significantly to enlargement of the liver and spleen. As the liver and spleen increase, abnormally, in size, the growing cell mass begins to compress blood vessels (particularly veins) and lymphatic channels, resulting in 'congestion' (retention of blood and fluid) of these organs, contributing to further enlargement and accelerating the ‘congestion’ in a vicious cycle.
Severe anemia in Rh-disease rarely occurs before about 20 weeks, although the fetal RBCs strongly express the Rh-antigen by 30 days’ gestation. Many factors play into the risk for severe anemia including the maternal antibody titer, the type of IgG antibodies to which the baby is exposed, and the baby’s genetic background. Baby’s can usually tolerate very low RBC counts. However, when the anemia becomes so profound that the baby’s ability to supply oxygen to its tissues diminishes, the baby begins to accumulate lactic acid as the consequence of having to use metabolic pathways to support its tissues that do not require oxygen (anaerobic metabolism). The resulting ‘acidosis’ is probably one of the primary mechanisms by which the fetal heart begins to function less efficiently and, if this continues long enough, the baby goes into ‘heart failure,’ resulting in the terminal stages of Rh-disease (unless corrective measures are taken) in which the baby retains fluid throughout its body, a condition called hydrops fetalis. It is also thought that the congestion of the fetal liver, by impairing venous blood flow from the placenta to the heart (remember, it is the umbilical vein, not a high pressure artery, that carries oxygenated blood from the placenta and through the fetal liver before going to the heart) contributes to the heart failure as well.
There is at least one other event that occurs during Rh-disease that can put the baby at long-term risk for complications, or even death. When the baby’s RBCs break down and release hemoglobin, the hemoglobin is then also broken down, primarily into a substance called bilirubin. Indeed, elevated circulating levels of bilirubin can usually be detected even before the baby begins to develop anemia. Some of the bilirubin is converted into a ‘water soluble’ form that can be excreted in the fetal urine and, as we will discuss in the final post on this subject, the detection of this becomes the basis for assessing, indirectly, the degree of fetal anemia. Unfortunately, due to the immaturity of its metabolic pathways, the baby is not very efficient at converting bilirubin to this excretable form and a water insoluble form of bilirubin can begin to accumulate in the fetal blood. This form of bilirubin, called indirect bilirubin, has the ability to penetrate the lipid membranes of nerve cells and is toxic to them, causing cell damage and death. At extremely high levels of bilirubin, the baby can suffer permanent brain damage (kernicterus) and death as a result of that damage, but this is rarely seen today with the management protocols currently used to follow pregnancies and the babies who are the products of Rh-sensitized women.
I fully realize that today’s post is fairly complicated (it is even for most providers), but having a basic understanding of Rh-disease is essential to understanding the options (and importance) for evaluation and management of an Rh-sensitized pregnancy that will be presented in my next post on this subject…
35 Comments:
At Sun Apr 29, 11:22:00 PM 2007,
Anonymous said…
As i am a mother and am also o negative I found this article extremely enlightning and appreciate the effort to educate the laymen. Thankyou
At Mon Apr 30, 01:52:00 PM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
Thank you for reading and I am glad I could help. If you have any other topics you would like to hear discussed on this site, please feel free to write back and let me know. No question is 'too basic!'
At Wed Jun 06, 08:32:00 AM 2007,
Anonymous said…
I am a mother of a daughter with hydropsfetalis..she is now 17 and i have always believed and trusted the doctors that told me why she was born the way she was..and never given much room for doubt . , i am rh negative ,but never was i told that this may have caused my daughters condtion and have always thought that the two were totally unconnected...i am sure i had the anti bodies jab after she was born but never during pregnancy.i have spent most of my daughters life worrying that maybe it was something i had done. i was told there was a possible leak in her lymphatic system that most likely caused her to be born this way ,,but after reading your pages ,it makes me wonder why my medical team never put the rh factor and her sypmtoms together ,,and all the syptoms i have read about are on your pages exactly how she was born .
i hope you read this as it may be as intresting to you as it is to me ..thank you linda jameson1@hotmail.co.uk
At Wed Jun 06, 10:46:00 AM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
Linda, there are lots and lots of things that can cause hydrops fetalis (isoimmunization, parvovirus infections, fetal abnormalities, chromosomal problems, etc....). You are not to blame for any of these, so don't kick yourself over what happened. Thanks for reading and for your comment!
At Sat Aug 11, 03:26:00 PM 2007,
Anonymous said…
I am a O- Rh Positive mother and I never knew it was this bad. But my oldest son who is now 35, was born with Asperatic Pneumonia, was already losing weight and never moved around like I had heard babies do. In fact, I had a test to see if the baby was alive. But after reading this article, I have to ask if you think his illness at birth was related to the Rh factor? I was due the 7th of April and he was taken by C-Section on May 17. In fact the doctors stopped my labor and said he was too small and hadn't turned yet. He was born breech.
At Tue Aug 14, 07:00:00 PM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Anonymous Aug 11: No, I do not think your sons problems were related to Rh incompatibility. Thanks for your question. Dr T
At Sun Aug 19, 08:59:00 AM 2007,
Susan Corral said…
I was looking for information on the spleen as I have discomfort in that area. I am also RH negative and was fortunate to have the doctor who cared for me through my pregnancies treat me with the antidote to prevent any problems for my children.
So when I ran into your article I was interested if there are any connections between my RH negative blood type and the condition of my spleen today? The general information on the spleen I find on the internet doesn't seem to fit me or my lifestyle, as I am 64, take no meds, and am a yoga practitioner. I did take HRT for some time and have an inherited tendency for varicose veins though.
Any comments you have would be appreciated. Thank you so much!
STC
At Tue Aug 21, 07:02:00 AM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
To STC Aug 19: With left upper quadrant pain at age 64, I would be much less worried about your spleen, and more worried about other possibilities such as a heart condition, stomach or bowel problems, etc. You should see a doctor soon to have her/him gather the appropriate historical information, perform a thorough physical exam, and to recommend diagnostic studies to properly evaluate you for this discomfort. This is NOT at all related to your Rh-negative blood; I can tell you that with certainty! Best wishes and thank you for reading.
At Mon Oct 15, 02:11:00 PM 2007,
Anonymous said…
Hi. I recently just had my first child and and became RH sensitized during the pregnancy. I unfortunately did not receive RhoGam at 28 weeks and formed antibodies later in the pregnancy. My tighter levels are high, which I have been told by a doctor means I would be at higher risk for subsequent pregnancies.
My question is, what are the alternative options for couples who have this problem? I have read a little about invitro methods and pre-genetic diagnosis of embroyos, and that this might be an option if my partner has at least one component in his blood that is not RhPositive.
Is there any way to test sperm prior to using it to see what the blood type is? I know that this question may seem way out in left field, but I know that there are new methods coming out everyday and was just curious if there was any sort of new methods being tried out.
Thanks
At Fri Oct 19, 08:02:00 PM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Anonymous Oct 15: Your partner can have his Rh-status evaluated (heterozygous or homozygous) by simply having his blood evaluated (no need for sperm here). Sperm cannot be tested at this point to determine which may be carrying the genes for Rh and which are not. You are correct though, if he is heterozygous, then 50% of your children together will be Rh-negative and at no risk for complications to your Rh-antibodies. This can be done by prenatal genetic diagnosis but that is VERY expensive. It can also be done by CVS, amniocentesis, or percutaneous blood sampling - each being done at later stages in pregnancy. Or you can simply get pregnant and have doctors assess your baby's risk for anemia by Doppler flow velocimetry. With current technology, and intrauterine transfusions for Rh-affected babies, we are pretty good at getting you to the point of a good outcome during the pregnancy, although you may still have to be delivered prematurely. Why don't you have your doctor refer you to a Maternal-Fetal Medicine specialist in your area for 'preconceptional counseling' before you decide about getting pregnant again. Thanks for reading and best wishes! Dr T
At Fri Jan 04, 09:04:00 PM 2008,
SAD MOTHER said…
HELLO IAM A MOTHER OF TWO BOYS AND I AM ALSO O RH NEGATIVE,THIS PASS SEPTEMBER I GAVE BIRTH TO A STILL BORN BABY BECAUSE OF MY CONDITION,I WAS NOT AWARE OF THIS PROBLEM UNTIL THE BIRTH OF MY SECOND CHILD WHICH WAS BORN EARLY BY C-SECTION WHEN I WAS 8 MONTHS ALONG. WE WANT TO TRY AGAIN BUT IAM SCARED OF THIS HAPPENING AGAIN.CAN YOU PLEASE GIVE ME SOME ADVICE. THANK YOU
At Sun Jan 13, 11:14:00 AM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To SAD MOTHER Jan 4: I am corry for your recent loss. By "this condition" I am assuming that you are Rh-sensitized. Now that your doctors know this, there is a very good chance that you can get through a pregnancy successfully with careful monitoring of the baby and intrauterine transfusions if these become necessary. Best of luck to you and thanks for writing. Dr T
At Fri Jan 25, 04:31:00 PM 2008,
Marci said…
I was diagnosed with Rh disease after I had my first child and then a miscarriage. I was still able to have another child after being closely monitored throughout my pregnancy. My second child was born at 36 weeks and she was mildly anmeic. She had two blood transfusions and was in NICU for two weeks. I would really love to have another child, is there any way? I don't want to put a baby in harms way. My husband has been tested and we are not compatable. I just want to check all of my options before giving up for good. Thanks
At Mon Jan 28, 06:11:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Marci: Although you had a complicated pregnancy the last time, both you and the baby got through it. If you want another pregnancy, just be aware that it will also be complicated, but in experienced hands, you have a very good chance at another good outcome. The baby might need intrauterine transfusions, or need to be delivered even earlier, but if you understand the risks, follow your heart. The only other option (I am presuming your husband is D/D homozygous and that's what you meant by "incompatible") is to find an Rh-negative sperm donor. Then your baby cannot be Rh-positive and should have no complications related to your isoimmunization. Best wishes and thanks for reading. Dr T
At Wed Apr 23, 09:44:00 AM 2008,
Anonymous said…
hiya, i have a son who was born with fetal hydrops.hes nearly five now and has delayed development we never found out the cause of the hydrops.I had loads of test and nothing could be seen as to why he got the condition.
I am with a new partner now but i am worried of this happening again.what are the chances of it happening again?
shell
At Thu Apr 24, 06:39:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
Hi Shell: It would sure help if we had a diagnosis! Your son might have had a congenital infection, most likely CMV, assuming he does not have a chromosomal abnormality or a genetic condition. I would guess the chances are small that it will happen again. If it does, let me klnow! I wish you the best of luck! Dr T
At Wed May 14, 07:17:00 AM 2008,
Anonymous said…
I am 35, and had a severe case of Rh disease when I was born (when the Ig was still new) - I'm wondering if any studies of long term effects have been done? (esp. Regarding the liver)
At Thu May 15, 06:00:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous May 14: First, I am curious, what sort of liver problems do you have? I am not aware of any long-term liver complications related to severe Rh-disease, but then again, perhaps no one has asked the question before! I will let you know if I can find out anything. Thanks for a great question! Dr T
At Wed Jun 11, 01:51:00 PM 2008,
Anonymous said…
I am A- (husband positive)with a healthy 3 year old and I have just had miscarriage and am producing anti bodies, even with rhogam shot after first pregnancy and after miscarriage. Are there very high chances of complications, and what type of specialist can assist my gynae/ob.Thank you for the article Leigh South africa
At Sun Jun 15, 09:22:00 AM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous June 11: The risk of future complications depends on the antibody titer and the fetal blood type. A specialist in Maternal-Fetal Medicine should be consulted BEFORE your next pregnancy to answer all of your questions and to assess your risks. Thanks for writing. Dr T
At Sun Jun 15, 11:26:00 AM 2008,
Anonymous said…
Thank you for the reply, I will take your advice.. No one I know has been through this or knows about it thank you for your help, Leigh
At Mon Jun 16, 10:36:00 AM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Leigh: You are welcome and let us all know what you find out in your case! Best wishes. Dr T
At Sat Jun 21, 12:54:00 AM 2008,
Anonymous said…
Please can i ask one more question which you might have covered but I missed. If I had the Rhogam on the Saturday after three weeks of bleeding with the natural miscarriage, and then had the blood test on the Monday (approx 36 hours later) could that have affected the result or is it a straght yes and no to producing anti bodies. Thank you again Leigh, SA
At Sat Jun 21, 06:19:00 AM 2008,
leigh said…
Sorry one more question, if you have time. Could the Rhogam shot I received on the Saturday evening have affected the blood test i took the Monday morning in anyway (showing anti bodies)? (yes am trying to find a glimmer of hope! And can the level of seriousness of sensitisation be checked before falling pregnant(sorry if I missed this on your previous posts) :) Not many maternal fetal specialists seem to be here in Johannesburg but still looking, leigh SA
At Tue Aug 05, 10:46:00 AM 2008,
Anonymous said…
My wife has to go for a scan to determine anemia in the womb tomorrow due to a find of antibodies in her blood detected at 34/35 weeks. All notes relating to RH disease refer to the mother having RH negative and Baby with RH positive, Do you have the same effect (IE risk of rh disease) if its the other way round, ie Mother RH pos, baby RH neg. notes from our last pregnency show my wife has 'A RH Pos' Blood? However she did have a tranfusion at the last birth. Surley you cant swap from rh pos to neg...can you. Thank you in advance for any responce.
Regards
Craig (Worried Dad)
At Thu Aug 07, 07:28:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Leigh June 21: Sorry, this is the first time I have seen your questions. Yes, the rhogam shot probably gave you the positive antibody screen. Have the antibody screen repeated in about 6 months to see if you really are sensitized. Dr T
At Thu Aug 07, 07:32:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Craig: No, you can't switch from Rh-postive to negative. Your wife probably became 'sensitized' to another blood antigen (or to an Rh-antigen that she does not carry herself) as a result of the transfusion. Under those circumstances, if the baby carried that antigen on its red blood cells, and it is one that can cause the break down of the baby's red cells in the presence of you wife's antibody, the baby could still be 'at risk' even if it is Rh-negative. Please ask your wife's doctor what antibody she has developed. Good luck and please let us know. Dr T
At Fri Aug 08, 06:00:00 PM 2008,
Anonymous said…
Hi, I have a healthy son who is 9 years old. I had a rhogam shot after he was born so I'm assuming I'm RH- . He was healthy other then a mild jaundice. After having him I split from my ex and had 2 abortions with my bf who is now my new husband. After the 2nd I'm sure I had the shot but can not remember if they gave me one after the first abortion. We now want to try to conceive. If I did not recieve the shot after the first abortion have I def been sensitized? If so is there anything I can do before actually getting pregnant to lessen the risk of complications? Thank you.
At Tue Aug 12, 07:44:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous Aug 8: No, sensitization is still rather uncommon with first trimester pregnancy losses and terminations, so you may not have become sensitized. Simply ask your doctor for a "blood type and antibody screen" and that should answer your questions. Dr T
At Tue Aug 19, 03:28:00 PM 2008,
Tracy said…
I was found to be positive for protein m antibody during pregnancy, doc said very rare nothing to worry about the chances of it being igg very rare. At 34 weeks I gave birth via c-section to a hydropic baby with down syndrome. They say the downs caused it and I cant beleive it, m antibody was igg. My daughter had no heart problems or defects from the downs to cause this phisiological response. I had 2 bleeds during pregnancy 8/3/07 and a heavy bleed on 8/30/07, I beleive this is when process started. I gave birth to a severely hydropic baby approx. 23 days after last bleed. She survived this fatal disorder and so far is doing well. Can you help me or quide me in the right direction to find out the truth???
At Fri Aug 22, 09:55:00 AM 2008,
Anonymous said…
Thank you for the reply Dr T, I found a group on facebook which has other women who have had pregnancies with the RH problem and it has been wonderful support..i felt so alone..Thanks to your advice as well it is frightnening that we have discovered many midwifes know nothing of the rh anti bodies and the facts! Thanks again Leigh x
At Fri Aug 22, 05:26:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
Tracy: Down syndrome alone, even in the absence of a major cardiac defect, can cause hydrops for reasons that are unclear and most likely related to metabolic disturbances. They should have been able to tell at birth if the anti-M antibodies caused the problem because the baby would have been severly anemic if your isoimmunization had been the cause. Ask the baby's doctors about the laboratory evaluation and results the baby had after delivery. They will explain things to you if you ask. Glad to hear the baby is doing better now. Dr T
At Tue Aug 26, 06:40:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Leigh Aug 22: Thank you for the kind words and for reading. Regards, Dr T
At Wed Sep 24, 09:26:00 PM 2008,
Anonymous said…
My husband and I are adopting a severe hydrops baby (RH). She lived in the NICU for 3 months and then we brought her home. I am told they did not think she would live for the first week. They had to leave a continous drain in her, she was on a breathing machine, enlarged liver and spleen, 4lbs 4oz 2 lbs of this was water. I can not find the long term effects of hydrops anywhere. We believe ther is neurological damage and she has feeing issues. Where do I look on the net for the long term effects?
thanks, from MT
At Tue Oct 07, 11:41:00 AM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To MT Sept 24: Not all babies with hydrops end up with neurologic damage, but if your baby has feeding problems, it may well have had some. The type and extent of damage depends on the underlying cause. In your baby's case, the two most likely causes are hypoxic-ischemic brain damage from too little oxygen-carrying capacity in the blood as the result of profound anemia and/or kernicterus as the result of too much bilirubin in the blood as the result of the fetal red blood cell destruction. I am sure the neonatologists who took care of the baby can tell you which of these was their primary concern or if there was another possible reason for brain damage that might have even occurred after the birth. Best wishes. Dr T
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