Red Blood Alloimmunization

All human blood shares certain similarities. We all have red blood cells, white blood cells, platelets and plasma, and we all inherit one of four different blood types from our parents:

• A
• B
• AB
• O

Despite these common characteristics, each person’s blood has certain distinct features passed to us through both parents’ genes. Our red blood cells, for example, have distinct markers called antigens. This combination of markers explains how the body can distinguish red blood cells that belong to us from those that do not. 

One of these markers is a protein called an RhD factor—or Rhesis factor. Some people have the RhD factor; others don’t. This difference is so important that it further divides the four blood types into eight—those that have it, and those that don’t. 

Blood types that have the RhD factor are called positive and blood types that don’t are called negative. No matter what type of blood you have, you are either positive or negative. (This expands the blood types to include: A positive or A negative, B positive or B negative, AB positive or AB negative, and O positive or O negative.) Most people are RhD positive.

The reason these markers are so important to health is that they are linked to our natural immune system, which alerts the body to anything foreign. When the body is exposed to germs or cells that are different from our body's healthy tissues, an antibody is created to fight it. 

This can become a health issue during pregnancy if a mother’s body regards her unborn baby as foreign—which can happen when a baby inherits a blood type from the father that is different from the mother’s. If so, a pregnant woman may produce antibodies against her baby's red blood cells—a maternal condition known as red blood cell alloimmunization, which can occur with RhD and a range of other antigens.

• Severe anemia
• Decreased oxygen levels
• Fluids in the unborn baby (hydrops fetalis)
• Heart failure 

In some cases, it can even lead to fetal death. Fortunately, the number of fetal deaths due to red blood cell alloimmunization has decreased significantly, due to new detection and treatment options. 

Pregnant women with complications from red blood cell alloimmunization can get expert care from maternal-fetal specialists at Riley at IU Health. Our specialists have the skills, experience and training to guide expectant mothers and their babies from pregnancy to delivery and beyond. This includes any neonatal care that may be needed afterwards. Our Level 4 Neonatal Intensive Care Unit (NICU) is Indiana’s only comprehensive NICU—the state’s highest level of neonatal care. 

Sensitization: The Body’s First Response to an Unfamiliar Antigen

The first time the body encounters an unfamiliar antigen there may be little or no response. This is called sensitization. Women most often become sensitized to a different blood type during a pregnancy or after a blood transfusion. 

Sensitization can also occur naturally or through another cause, such as:

• Blood transfusion
• Previous fetal-maternal hemorrhage after an ectopic pregnancy (one outside the uterus) or abortion
• Procedures such as amniocentesis, chorionic villus sampling, or dilation and curettage (D&C)—a procedure to remove tissue from inside the uterus 
• Sharing needles

Although the first response may be small, the body may form antibodies to attack more aggressively the next time these foreign antigens are introduced. This can cause problems for later pregnancies because the antibodies are ready and waiting to attack.

An Example of Alloimmunization: What Happens with the D Antigen

If an expectant mother is RhD negative, but the father and the baby are RhD positive, sensitization may occur during her first pregnancy. When her body encounters the RhD antigen again in a later pregnancy, the antibodies she developed earlier may cross the placenta and attack her baby’s red blood cells—a condition known as hemolytic disease or HDFN. 

When this happens, the fetus can become mildly to severely anemic and have a low blood count. This is significant because red blood cells deliver oxygen to nourish the fetus. An unborn child’s heart may work harder and create a situation similar to heart failure in an adult. In serious cases, the fetus may build up fluid—a condition known as hydrops fetalis. Together, these effects can be life-threatening for a fetus

Diagnosis of Red Blood Cell Alloimmunization

All pregnant women have prenatal blood tests  to detect alloimmunization as part of routine prenatal care. If antibodies are detected, an expectant mom may be monitored throughout her pregnancy to check for increased antibody production. Fathers may also be tested to see if they share the same antigens with the fetus. For example, if a mother is RhD negative, a test of the father could show that he is RhD positive, which could result in an RhD positive fetus. 

More extensive testing may be required to monitor the fetus, including ultrasound-guided fetal blood sampling, chorionic villus sampling (CVS) or amniocentesis. Various types of ultrasounds may be performed to check an unborn baby for signs of hydrops (an accumulation of fluids that suggests severe fetal anemia) and to measure fetal blood flow. A Middle Cerebral Artery (MCA) Doppler study, for example, can measure the speed of blood flowing through your baby’s brain starting at about 18 weeks, and it may be repeated every one to two weeks. If blood flows too quickly, severe anemia is more likely. Collectively, these tests can help physicians decide how to approach treatment of an expectant mom and her unborn child.