Welcome

Welcome! You've just landed at the most complete resource for families dealing with Isoimmunization on the web. We're sorry you were diagnosed with antibodies during your pregnancy, but we are glad you're here and we will be happy to help you in any way that we can. Finding out you have antibodies is a scary thing, but it doesn't have to be! Armed with the right knowledge, you can be informed about your baby's condition, and be a partner in your baby's health. If you're pregnant, pop on over to the Pregnancy page where you'll find information about testing, risks, and options (yes, there is good news!). If you're getting close to birth, check out the Birth page for more info on what needs to be done around birth. No matter where you are on your Iso journey, there's always Things to Think About. There's also some Info that's helpful to everyone. 


We now have an awesome support group called, "Support For Antibodies In Pregnancy" to help you on your journey from before pregnancy all the way through after birth. You can join us here and we can get you hooked up with an Antibody Buddy - someone with your same antibody. This is a fast moving group of hundreds of moms, so expect to get responses the same day (sometimes even within minutes). We've got moms in here who have had several pregnancies with antibodies and who have years of experience, so don't be afraid to ask. No question is too silly or too small if you're wondering about it. Don't forget to like and follow our Facebook page, Isoimmunization (@AllAboutAntibodies) to stay up to date on new information and feature articles too. 


Whenever you see a number in parenthesis (1), it's a reference number. You can look this number up on the References page and see the exact medical article the information was sourced from.

This page exists to help women advocate for their babies. We do this by providing information to moms so they can better understand their disease; by increasing understanding of isoimmunization; and by raising public awareness about isoimmunization. All About Antibodies empowers women to be partners in their prenatal care. We are sharing information today to save the lives of tomorrow.

There Is Hope!

With proper treatment, you have every reason to expect a live baby. Isoimmunization is not a death sentence for your child. 

There are new and proven treatment methods. We have great ways of monitoring baby now and several options for helping earlier than ever. 
Your baby is not automatically going to be anemic, brain damaged, or anything else. You can have a perfectly healthy baby who will turn into a normal adult. 

You can have more children. 

SPECIAL ALERT!

There's a new clinical trial going on for pregnant women with anti-D and anti-Kell antibodies. Many doctors do not know about this study, so if you think you are a candidate, please follow the link below to print the information and get it to your doctor ASAP. 

M281 Trial Criteria

  • Anti-D antibodies with a titer of 1:32 or higher     - OR -   anti-Kell antibodies with a titer of 1:4 or higher. 
  • Between 8 and 13 weeks gestation.
  • Previous pregnancy with problems occurring at or before 24 weeks including: 
  • Severe anemia at the time of IUT    - OR -
  • Hydrops fetalis with MoM over 1.5     - OR -  
  • Loss with placenta/pathology reports indicating severe HDFN.

Please visit  https://clinicaltrials.gov/ct2/show/NCT03842189?cond=m281&rank=3 for more information about the M281 trial and contact information for the study. Sites are opening up all the time and they will pay for travel expenses and lodging. 

What Is M281?
M281 is a monoclonal antibody that is also called  Nipocalimab. It is designed to prevent Hemolytic Disease of the Fetus and Newborn by reducing how many antibodies are in mom's system (lowering titers), and by blocking the antibodies from crossing the placenta. It is an IV infusion given every week. While the study is only for anti-D and anti-Kell, the two most aggressive antibodies, it should work for all antibodies once the trial is finished and the drug given final approval. 

Additional Links:
https://www.uth.edu/news/story.htm?id=2a52b16f-5f73-4fb7-bbd1-9bfb2aa967ff&fbclid=IwAR1SfU2g5luZvt-bNAeDo0Ah9lSWE2P9aTktAYLx8JHxegtEqwk-7TUK_D
https://www.empr.com/home/news/drugs-in-the-pipeline/nipocalimab-gets-fast-tracked-for-hemolytic-disease-of-the-fetus-and-newborn/

An Overview of Isoimmunization

What is Isoimmunization (Iso)?

Isoimmunization (also called alloimmunization), occurs when a woman’s immune system is sensitized to foreign blood cell antigens. This causes the woman to make antibodies that cross the placenta and destroy baby's blood cells (1).

During pregnancy, some of the mother's antibodies are transported across the placenta and enter the fetal circulation. This is necessary because newborns have only a primitive immune system, and the presence of maternal antibodies helps them survive while their immune system matures. A downside to this protection is that by targeting fetal blood cells, maternal antibodies can also cause HDN (2). Blood production in the fetus begins at about 3 weeks, and the baby's blood cells can have antigens on the red cell membrane as early as 38 days after conception (4).


Antibody? Antigen? What’s my body doing again?

Antigen – foreign protein on red blood cells of dad or baby

Antibody – made by mom to defend her body from the antigen

Antigens are foreign. Antibodies defend the body.


How it works

Dad makes the E antigen and passes it to baby. When baby’s blood and mom’s blood mix, mom’s blood finds the foreign antigen and makes antibodies to defend her body. This is called sensitization. The antibodies then find the foreign cells and destroy them in a process called hemolysis (hemo = cell, lysis = death). The next time mom’s sensitized body finds the E antigen, her antibodies are primed and ready to attack the foreign cells. So when mom has baby #2, who has dad’s E antigen, her antibodies cross the placenta and attack the baby’s blood.



A visual of how antibodies need to match their antigen on the blood cell or they cannot bind. The blood cell has 3 antigens - a star, a diamond, and a hexagon. The pink antibody has diamond shaped receptors, so it needs a diamond antigen to grab onto. No matching antigen = no attack. If the antibody does not have anything to grab on to then it cannot attack the cell. 

How did I become sensitized?

The most common ways maternal sensitization occurs are (1):
Blood transfusion

Birth

Abortion

Ectopic Pregnancy

Fetomaternal hemorrhage

Placental abruption

Amniocentesis

Chorionic villus sampling

Percutaneous umbilical blood sampling

External cephalic version (trying to turn a breech baby)

Manual removal of the placenta (instead of spontaneous delivery of the placenta)


Why is Iso dangerous?

Isoimmunization is dangerous because the antibodies can cross the placenta during pregnancy and if the fetus is positive for the specific antigens, the fetal red blood cells are destroyed. This can result in anemia, hemolytic disease of the newborn (HDN), fetal hydrops (sometimes fatal), and more (1).


Possible Outcomes

If you are sensitized, it is NOT a death sentence for your baby, and it does not mean you cannot have additional children. Advancements in fetal surveillance and treatment allow for successful outcomes for most of the affected fetuses.  For the Rh D- woman, the drug Rhogam has reduced the risk of sensitization to less than 1% of susceptible pregnancies. Because of this other alloantibodies have increased in relative importance. These include antibodies to other antigens of the Rh blood group system (ie, c, C, e, E) and other atypical antibodies known to cause severe anemia, such as anti-Kell (ie, K, k), anti-Duffy (ie, Fya), and anti-Kidd (ie, Jka, Jkb) (1).


How do I know if I have an antibody?

There is only one way to know if you have an antibody, you have to get tested. Routine antibody screening is done in the US on all pregnancies (unless refused) as part of the basic prenatal blood work.


The Exception
The exception to this is if you have had Rhogam recently. Rhogam can stay in your system for months, and usually will not titer higher than 1:4. In this case, your test may be reading the Rhogam antibodies, and not antibodies produced by your own body. If you are going to get Rhogam (please, please get it), then have an indirect antibody screen run before you get the shot. 

What do I do? Where do I start?

Start by keeping a binder or folder. Use this to write down all your questions (and the doctor's answers). No question is silly. It is important that you are informed and able to actively participate in your care and advocate for your baby. Ask for copies of all your test results and keep them in your folder. Don't forget to get a copy of each ultrasound report and MCA scan (complete with all the PSV values, not just the highest or lowest). This way you can see how things are changing and how baby is doing. This is also helpful if you have to have multiple doctors. Sometimes things don't always get passed along between offices, so it is very important to have your own record. It is also a great place to put keepsakes such as ultrasound photos, bracelets, etc. Consider having someone come with you to tests and appointments for support or to drive you home after procedures. The printables on the Info page are a great place to get started with things to put in your folder. 


You also need to get a medical alert card for your wallet or a medical alert bracelet. Mine says “Transfusion Alert: Anti-E”. This is important even after you're not pregnant. If you are ever in an accident or unconscious and need blood, you do not want to have a life threatening transfusion reaction. Some blood banks, hospitals, or doctor's offices will provide them for you. There are also multiple places online (eBay, Etsy, Amazon, etc) where you can order a bracelet, or in the pharmacy section of our local Meijer, there is a USB medical alert card that you can put your entire medical record, not just your antibody status. Some cell phones have an In Case of Emergency or ICE section where you can write your antibody status and include emergency contact information for your MFM too. I’ve attached a printable medical alert card here, and there's one in the Pregnancy Pack .
 

First Steps

As a quick recap:


Step 1: Get a medical alert card or bracelet. There’s one on the Info page.


Step 2: Start a notebook or binder.


Step 3: Get your current titers.


Step 4: Get a referral to MFM for a treatment plan. Ask questions such as:

          How often should we draw titers?

          When should I come back? When titers reach 1:8?

          Will you consult with other doctors?
          When will we start MCA scans?

          How often will we do MCA scans? Every week?
          When will we start BPPs? How often will we do them?
          When will we start NSTs? How often will we do them?
          Is IVIG an option? 

                    What is the earliest start for IVIG?

                      What is the latest start date for IVIG?
          Will the Dr do IUTs?
                    How many IUTs have you done? 
                    What is your success rate? 
                    What is the earliest the Dr can do IUTs?

                    What is the latest the Dr will do IUTs?

          Will the Dr induce? 
                   Induce at _____ weeks if titers are below critical.
                   Induce at _____ weeks if MCAs are good.

                   Induce at _____ weeks if MCAs are bad.


Step 5: Talk with your doctor about the M281 trial. Print off the trial page and bring it in with you when you ask for that referral to the specialist. Ask if you meet the criteria. Even if you do not, give your doctor the information - you never know, it might save the next patient's baby. It never hurts to make people aware of the new and developing treatment options that are out there. 


While You Wait

While you wait for that MFM referral, get some more blood work done on dad and baby. Get dad's antigen phenotype tested. It will give you two letters. You're looking for something that says EE or E+e-, or homozygous E. However it is phrased, it should tell you about Dad's antigen pair, not just one letter. This test absolutely should not be an antibody screen like they do on pregnant women. Below are some examples of the right test and the wrong test that were run on actual dads and shared in the Facebook group with permission. If Dad is negative for the antigen, then he cannot pass it on to baby. If baby is negative for the antigen that matches mom's antibody, then baby will be safe. 

If you have anti-D, anti-C, anti-c, anti-E, anti-e, or anti-K you have another optional blood test. This test can save you time, money, and unnecessary stress. It is called the cell free fetal DNA test or cffDNA for short. This is a blood test where they take mom's blood and find tiny bits of baby's DNA in it. The DNA is isolated and they are able to identify baby's blood type and antigen status (as well as boy/girl). This test is wonderful for women whose anti-Kell may have come from a transfusion, and for those with heterozygous partners. If a woman with anti-Kell has this test done, and it comes back that baby is Kell -, then she does not need extra appointments, costly ultrasounds, or the added stress of an isoimmunized pregnancy. She can have a perfectly normal pregnancy and delivery. Again, if baby is negative for the antigen that matches mom's antibody, then baby will be safe. 

In the US the test is called Sequenome Sensigene (for anti-D moms only). You also have the option of sending blood overseas to the UK or Netherlands. cffDNA testing is now being done in Australia as well as some parts of Canada. Visit the cffDNA page for more information about testing around the world including instructions and forms.

 

Remember...

With proper treatment, you have every reason to expect a live baby. 

We have great ways of monitoring baby now and several options for helping earlier than ever. 
Your baby is not automatically going to be anemic, brain damaged, or anything else. 

You can have a perfectly healthy baby when this is over. 

You can have more children. 

Next: Pregnancy

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