Alloimmunization and HDFN

Understanding your disease is so important to helping get your baby here safely. This page will provide an educational explanation of the disease and what is going on inside your body. As always, discuss everything with your health care team. 

Alloimmunization

The technical name for when mom makes antibodies

When a person (men can become alloimmunized too) is exposed to a blood type that is different from his/her own, the body recognizes the foreign blood and creates antibodies to remove it. This is a natural part of your immune system and works very well for fighting off viruses and bacteria, however the body also uses this system to cleanse itself of any foreign blood cells. When this happens in a woman, she can make antibodies that can cross the placenta and destroy baby’s blood cells 1. While there are several kinds of alloimmunization and antibodies that can form (red blood cell, white blood cell, and platelet), when we use the term on this website, we are referring to alloimmunization against red blood cell antigens.

For these examples we will use anti-E, but the information applies to any red blood cell antibody. Just swap the E with whatever antigen you need to. Anti-E is an antibody that is made when you are exposed to the E antigen. You can be exposed through blood transfusion, pregnancy, shared needles, or some antibodies can even be naturally occurring. Regardless of how you were exposed, the antibodies can cross the placenta.

Pregnant women are routinely checked for antibodies at their initial prenatal blood work and again at 28 weeks. Sometimes they are tested again at delivery. If your antibody screen comes back positive, you are considered alloimmunized. There are a few antibodies for which the antibody screen may come back negative, but the baby still be affected. These are anti-Dia, anti-Dib, anti-Jsa, and anti-Wra.

Hemolytic Disease of the Fetus and Newborn

The technical name for what the baby has

During pregnancy, some of the mother’s antibodies are transported across the placenta and enter the fetal circulation. If this happens, the antibodies will look for the specific antigen that they are matched with – our anti-E antibodies will look for the E antigen. Antibodies and antigens fit like a lock and key, the E antibodies can only attach to the E antigen, not the little e antigen, not the K antigen, only the E antigen. 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.

If the baby has the matching antigen, the mother’s antibodies will target the fetal blood cells and kill them. This causes Hemolytic Disease of the Fetus and Newborn 2. After the antibodies have crossed the placenta, they will latch on to a blood cell with the matching antigen and destroy it. That is their only job, to kill things that do not belong and remove them from the body. If the antibodies destroy too many blood cells, the baby becomes anemic. Untreated anemia can be fatal. To prevent this, a critical titer of 16 was established. In a first affected pregnancy, if the titers remain below 16, the antibodies are unlikely to cause moderate-severe anemia and the baby does not need additional monitoring. If you have a titer of 16 or higher, then the baby is considered at a higher risk for anemia and you receive weekly MCA scans. These MCA scans are special ultrasounds to check for anemia. If the MCA scans show a high value, the doctors give baby a blood transfusion. Current medical literature from multiple countries and sources (6 total) all recommend delivery at 37-38 weeks regardless of what your titer levels are. Even if your titers are low, even if your titers are stable, even if your MCA scans are good, after 37 weeks there is more risk to keeping the baby in than out.

If you have a baby who is antigen positive, the risk does not end at birth. All of the antibodies that had already crossed the placenta stay in the baby’s blood stream after the cord is cut. These antibodies can survive and continue to destroy the baby’s blood cells for up to 12 weeks, so many babies have weekly monitoring until then. After birth HDFN can cause high bilirubin levels, anemia, neutropenia, and thrombocytopenia. All of these potential complications are treatable, but without the monitoring listed in the medical literature, all of them can cause lasting damage or death.

If the baby does not have the matching antigen, the baby is completely safe and will not develop HDFN. This is the only way to 100% guarantee that baby will not develop HDFN. Even babies born to mothers with low titers can still have HDFN. Only antigen negative babies are guaranteed to not develop HDFN. Testing dad and/or doing cffDNA testing for baby’s E status is very important.


Do all antibodies cause HDFN?

Only some antibodies cause HDFN.

Antibodies that ARE associated with HDFN:
Diego: Dia, Dib
Duffy: Fya, Fyb*
Kell: K1, Kpa, k, Jsa, Jsb
Kidd: Jka, Jkb*
Lewis: Lea, Leb
MNS: M, S, s, N, U
Rh: c, C, Cw, D, e, E, G
Wright: Wra
Far
Gonzales*
Good
Lan
LW
Mta
PP1Pk (previously known as Tja)
Vw*
Zd

Antibodies that ARE NOT associated with HDFN:
Lutheran: Lua, Lub*
Wright: Wrb
Batty
Becker
Berrens
Coa-b*
Evans
Hil
Hunt
Hut
Jobbins
Jra
Mur
P
Rm
Ven
Xga
Ytb

*There have been cases of these antibodies causing HDN. Though rare, it does happen. Older lists available online will have these antibodies in the Does NOT cause HDN column, however this is no longer the case. Check the specific antibody page for more information.


How does it work?

We will use the example of a woman with anti-E antibodies. Every person has antigens on their blood. Before the antibodies were even formed, each parent produces antigens and passes the genetic code for these antigens on to their children. Dad carries the genetic code to make the E antigen and he passes it on to the baby. When the baby’s blood and the mother’s blood mix (through delivery, bleeding, or some other means), mom’s immune cells find the foreign antigen and sends out the alarm to start making 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 that the 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 also inherited dad’s E antigen, her antibodies cross the placenta and attack the baby’s blood.

Antibodies need to be an exact match for the 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)

For Rhesus negative woman, the drug RhoGAM has reduced the risk of sensitization to less than 1% of susceptible pregnancies.

What are the 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. Over 90-95% of babies with HDFN survive and thrive.

Key Terms

Alloimmunization – when a woman’s body makes antibodies against foreign red blood cell antigens.

Antibody – made by mom to defend her body from foreign antigens.

Antigen – proteins on red blood cells. If the baby has the antigen that matches mom’s antibody, she is at risk for HDFN.

HDFN – When maternal antibodies cross into the baby’s blood stream and attack his or her red blood cells. During pregnancy this can cause fetal anemia. After birth HDFN can cause high bilirubin levels, anemia, neutropenia, and thrombocytopenia.


I have antibodies, what do I do now?

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 printable care record is 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.


Remember…

  • You are your baby’s biggest advocate.
  • 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. 
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