As with most of my posts, this one begins with a story. Janie was referred to my office due to abnormal prenatal lab results. Specifically, she had a positive red blood cell antibody screen. This was her fourth pregnancy; her first two pregnancies and deliveries were uneventful. With her third pregnancy, she developed a positive antibody screen for an antibody called Kell, but her baby was born at term, healthy and strong. Now, with this new pregnancy, her Kell antibody level was positive in the first trimester. You may not be impressed by a positive antibody test, but based on her history and her labs, I was very concerned. Let me explain why, in this series of fun facts:
- Antibodies are proteins produced by our immune system. In general, they are a good thing. Their job is to seek and destroy foreign materials, like viruses and bacteria.
- Our red blood cells carry various kinds of proteins. Some of these proteins determine our blood type – A, B, O, etc. There are some lesser known red blood cell proteins that some of us have and some of us don’t. For instance, a fetus may carry a Kell protein (inherited from dad), and mom may not have this protein on her blood cells.
- In virtually every pregnancy, a small amount of fetal blood enters mom’s circulation. More blood can mix if mom has an episode of bleeding or placental separation.
Are you beginning to see how these random facts are coming together? If a fetus carries a Kell protein on its red blood cells, and a little fetal blood enters mom’s circulation, mom’s antibodies are activated. They destroy the fetal red blood cells, because their job is to protect mom from foreign “invaders.”
If the process stopped here, it would not be such a big deal. Chewing up a few fetal cells in mom’s circulation doesn’t hurt mom or baby, right? But the immune system does more than attack foreign material. Antibodies remember. In other words, if they see the same foreign material again, they respond faster, making more and more antibodies. (Interestingly, this is why mom’s antibody levels don’t tend to rise much with a first pregnancy, but are more dangerous with a subsequent pregnancy – antibodies are activated as soon as they recognize the Kell protein again.)
Now mom is carrying lots of Kell-hating antibodies (or Rh antibodies, or Duffy, or any of a number of red blood cell antibodies). This process is called “isoimmunization,” or “alloimmunization.” Some of these antibodies are small enough that they can cross the placenta and enter fetal circulation. Then they attack and destroy the fetus’ blood cells, because all of the fetal blood cells carry the Kell protein.
If enough antibodies are produced by mom, the fetus can become severely anemic – its red blood cells are being systematically destroyed. Severe anemia results in a condition called hydrops – the baby swells, and fluid collects in different areas of the body. More about this later.
When a red blood cell antibody is positive in pregnancy, there are several questions that we ask, before we assume that the antibody is positive because of the fetus:
- Has mom ever had a blood transfusion? If so, she may have received blood that was Kell protein positive, because donated blood is not routinely screened for Kell. If mom’s Kell antibody is present due to a previous blood transfusion, the baby may not be at risk for anemia, as long as the father of the baby does not have Kell-positive blood.
- Is the father of this pregnancy the same as with her previous pregnancies? If the father of a previous baby had Kell-positive blood, but the father of this pregnancy does not, the fetus should not be at risk, because baby will also have Kell-negative blood (if mom and dad are both Kell-negative, the baby has to be Kell-negative).
- Is dad Kell-positive? It’s a good idea to test Dad’s blood for the Kell protein. If he tests positive, there is up to a 50% chance of the fetus also being Kell-positive and therefore at risk for anemia and hydrops.
Ok, let’s go back to Janie. Her Kell antibody test was positive early on. Her boyfriend was the father of all her children, and he tested positive for the Kell protein. And remember, Janie’s Kell antibody first appeared during her third pregnancy. She was now pregnant with baby number four. This is the scenario that we worry about. After discussing how alloimmunization works, we made a plan for monitoring her pregnancy and her baby. We tested her Kell antibody level every month. As long as the level was very low, the baby’s risk of developing anemia should be low. Kell antibodies can be sneaky and unpredictable though, and fetuses can be harmed sometimes even with a low maternal antibody level. So we also watched the baby with ultrasound every month. In particular, we looked at blood flow in the baby’s cerebral arteries – if a fetus is becoming anemic, then blood will start flowing faster. When Janie was about 24 weeks along, blood flow through the fetal cerebral artery had become abnormally fast, and her Kell antibody level rose. Without intervention, the baby was at risk for severe anemia and hydrops.