Understanding the Terminology

More detailed information can be found about each of these terms elsewhere on the Allo Hope Foundation’s website. Utilize the search bar above for more information about a particular term.

A


ABO:

This abbreviation refers to the A, B, and O blood types. The blood types are decided by the presence or absence (O) of the A and B antigen proteins.

ABO Incompatibility:

The mismatch between a mother with type A, B, or O blood and her child who has type A, B or AB blood. If a woman has developed ABO incompatibility, she produces anti-A or anti-B antibodies. It is common for women with blood type O to be incompatible with their type A or B infants, or for a mother with blood type A to be incompatible with her type B child. 

Affected:

The fetus or newborn who has either a positive DAT, or is antigen positive, and who has signs of anemia, hyperbilirubinemia, or some other consequence of HDFN. It is not required that an infant be treated (via transfusion etc) in order for them to be considered affected.

Alloimmunization:

Alloimmunization is when a person makes antibodies as a result of foreign blood mixing. When this happens in a pregnant woman it is called maternal alloimmunization. These antibodies can can cross the placenta and attack the unborn child; a disease called hemolytic disease of the fetus and newborn or HDFN for short.

Amniocentesis:

A procedure where a needle is inserted through the abdomen into the uterus to draw out some of the amniotic fluid. The amniotic fluid can be tested for a variety of fetal health information including genetic abnormalities, gender, red cell antigen status and bilirubin level. If done incorrectly, an amniocentesis may raise antibody titer levels and increase the risk to the baby. Patients and physicians use noninvasive test options more frequently, such as cffDNA testing and MCA Doppler scans.

Anemia:

An inadequate amount of red blood cells. Anemia is commonly evaluated by checking the patient’s hemoglobin or hematocrit levels. Anemia in a fetus may present as an elevated MCA Doppler score (>1.5 MoM), hydrops, or ascites. Untreated anemia may result in organ damage, heart failure or death.

Anti-:

Shorthand for antibody, e.g., Anti-Kell, Anti-D, Anti-c.

Antibody:

Antibodies are free-floating proteins in the blood plasma that bind to foreign antigens in order to destroy cells that have the foreign antigens.

Antibody Boostering:

When an antibody undetectable during cross-matching is suddenly detectable again. Antibody boostering happens in patients who were earlier found to have alloantibodies, but then experienced antibody evanescence. Boostering can result in the antibodies coming back in an anamnestic manner, including hyperhemolysis.

Antibody Evanescence:

This term refers to when antibodies decrease to below detectable levels. Antibody evanescence poses a challenge in transfusion medicine and makes it more likely that an alloimmunized woman will have a hemolytic transfusion reaction when antibodies that are unknown to medical professionals resurge during antigen exposure. Once a patient develops antibodies, the antibodies never truly disappear. Fewer than 30% of antibodies are estimated to be detectable by current methods.

Antibody Test:

A method of checking for specific proteins in the blood that have been formed by the patient’s immune system.

Antigen:

Antigens are protein surface markers located on red blood cells. The term antigen comes from “antibody generating”. Everyone has antigens on their red blood cells.

Antigen Negative:

This partner does not have any copies of the antigen. There is 0% chance of this partner passing on the antigen. Children from this partner WILL NOT be at risk of developing HDFN.

Antigen Phenotype:

This test looks for the specific antigens on the red blood cell and will return a +/- or heterozygous or homozygous result. For example, the antigen phenotype may show C+c-. The antigen phenotype test can be done on the infant to determine antigen status, or on the father to determine his antigen status and help predict what antigens the fetus will inherit.

Ascites:

When fluid accumulates in the peritoneal cavity. This is visible on ultrasound or after birth as abdominal swelling and can be a sign of severe anemia. 

Autologous Blood:

This means that a patient donates her own blood to be given to herself. In rare cases, an alloimmunized patient may donate autologous blood for the intrauterine transfusion of her fetus. Special arrangements must be made with a blood bank for this donation.


Bhutani Nonogram:

The chart used for tracking bilirubin levels in the infant and determining if phototherapy, IVIG, or exchange transfusion is required.

Bilirubin (Bili):

A product that is produced when red blood cells are broken down. In the case of alloimmunization, they are broken down by the mother’s antibodies. Excess bilirubin can cause jaundice, kernicterus, hearing loss, tooth enamel problems, permanent brain damage or even death if left untreated.

Bilirubin-Induced Neurological Dysfunction (BIND):

Brain damage as a result of high levels of bilirubin.

Biophysical Profile (BPP):

An ultrasound that checks amniotic fluid levels, fetal breathing, movements, and tone. Often abbreviated as BPP.

Blood Type:

Every individual has one of 4 main blood types: A, B, AB, or O. These are based upon the antigens that exist on your blood. A patient may also be called Rh negative or Rh positive depending on the presence of the “D” antigen on their red cells.

Bronze Baby Syndrome

When the infant’s skin and mucous membranes turn grey-brown as a result of hyperbilirubinemia often combined with liver dysfunction.


Cell-Free Fetal DNA (cffDNA):

This noninvasive test uses the fetal DNA that is found floating in maternal circulation to check the fetal red cell antigen status. It requires a blood sample from the mother. cffDNA can be used for pregnancies complicated by anti-Kell, anti-D, anti-C, anti-c, anti-E, and anti-e antibodies.

Chorionic Villus Sampling (CVS):

A procedure where a needle is inserted into the placenta and chorionic villi are removed. This is commonly done to obtain fetal DNA. Due to the high risk of sensitization, bleeding, and other complications, CVS is contraindicated when maternal alloimmunization is present.

Complete Blood Count (CBC):

This is a laboratory test that checks the levels of a variety of blood cells and includes hemoglobin, hematocrit, neutrophil count, reticulocyte count, and more.

Cordocentesis:

The procedure is usually done as part of an IUT or (rarely) to determine the need for an IUT. The cordocentesis will confirm fetal hemoglobin/hematocrit and antigen status. This test is done by inserting a needle through the mother’s abdomen and into the umbilical cord to sample fetal blood. The procedure was previously known as “PUBS” or “percutaneous umbilical blood sampling”

Critical Titer:

The titer associated with a risk of developing severe anemia and hydrops. Below the critical titer, the fetus is at risk for developing mild to moderate, but not severe anemia.


Delayed Onset Anemia:

Anemia that is not present at birth, but happens between 2 and 12 weeks of age. Delayed onset anemia can be fatal if untreated.

Direct Antiglobulin Test (DAT):

This test looks for antibodies that are bound to red blood cells and is typically done on infants. With specific antibodies, this test can be negative even when the baby is still affected and needing treatment. These antibodies are anti-C, anti-c, anti-Fya, anti-Good, anti-H, anti-Jra, anti-M, and anti-Mta.

Direct Coomb’s Test:

See direct antiglobulin test.


Erythrocytes:

See red blood cell.

Exchange transfusion:

A transfusion done to prevent brain damage due to high bilirubin levels in newborns. During an exchange transfusion, blood from the infant is removed and replaced 1-2 times. Exchange transfusions are given if IVIG does not bring bilirubin levels down to a safe level.


Ferritin:

A blood test performed to measure the amount of iron in the bloodstream. Ferritin is the major iron storage protein. A ferritin test should be performed before iron supplements are given to infants with HDFN. Normal ferritin range for newborns is 25-200 ng/mL. The normal range for infants from 1-5 months old is 50-200 ng/mL.

Fetal Maternal Hemorrhage (FMH):

This is a bleed which allows or has the potential for blood to mix between the fetus and the mother. FMH is often detected using a Kleinhaur-Betke test.

Fetal Medicine Unit (FMU):

A team of high-risk doctors who specialize in pregnancy complications. This is the UK equivalent of a fetal center, where Maternal Fetal Medicine (MFM) specialists work.


HDN:

Hemolytic Disease of the Newborn. This was the older name for HDFN. The “F” was more recently added to indicate that the disease actually starts during fetal life.

Hematocrit (Hct):

Hematocrit is a blood test that measures the percentage of the volume of whole blood that is made up of red blood cells and is used as an indicator of anemia. The normal hematocrit range for infants 0-6 months is 37.4 - 55.9% for females, and 43.4 - 56.1% for males. A fetal hematocrit of less than 30% is considered anemia.

Hemoglobin (Hgb):

Hemoglobin is a protein in red blood cells that carries oxygen. A blood test can tell how much hemoglobin you have in your blood and is used as an indicator of anemia (common in the USA). The normal pediatric hemoglobin range for infants age 0-6 months is 12.7 - 18.3 g/dL for females and 14.7 - 18.6 g/dL for males.

Hemolysis:

Blood cell destruction. Hemo- blood, lysis - destruction.

Hemolytic Disease of the Fetus and Newborn (HDFN):

This is the official diagnosis for the fetus and for infants affected by maternal alloimmunization. Signs of HDFN after birth include a positive direct coombs test or positive antigen status and at least one of the following: anemia, hyperbilirubinemia, neutropenia, thrombocytopenia.

Hemolytic Transfusion Reaction (HTR):

Hemolytic transfusion reactions are serious complications from blood transfusions. In a patient with alloantibodies who receives blood not matched to their antibody status, transfused blood cells are destroyed by the patient’s immune system. HTR can result in the creation of anaphylatoxins, a systemic inflammatory response, hypotension, disseminated intravascular coagulation, diffuse bleeding, and disruption of microcirculation leading to renal failure and shock. Alloantibodies are the second leading cause of fatal HTRs.

Heterozygous:

This means that the patient’s partner has one copy of the gene and one copy of a different gene. In the case of the RHD gene, this test on the partner’s blood must be done through DNA testing at a special laboratory. The result is noted as “Dd”. If a partner is heterozygous, there is a 50% chance that the fetus will inherit the antigen. Testing for all other red cell antigens can also be done on the father’s blood.

Homozygous:

This means that the patient’s partner has two copies of the gene and one copy of a different gene. In the case of the RHD gene, this test on the partner’s blood must be done through DNA testing at a special laboratory. The result is noted as “DD”. If a partner is homozygous for the antigen, there is a 100% chance that the fetus will inherit the antigen. The partner can also be homozygous without the antigen (see antigen negative). Testing for all other red cell antigens can also be done on the father’s blood.

Hydrops:

Hydrops is the buildup of fluid in various fetal compartments including under the skin (skin edema), in the abdomen (ascites) and around the lung (pleural effusion). Some experts consider the presence of ascites alone as an early sign of hydrops. Alloimmune hydrops is the result of heart failure due to untreated anemia.

Hyperbilirubinemia:

High levels of bilirubin.


Immunoglobulins:

Proteins that are present in the blood plasma and in immune cells, which function as antibodies.

Indirect Antiglobulin Test (IAT):

This test looks for antibodies that are free floating in the blood plasma and is commonly done on the mother, though sometimes it is done on the baby to confirm the presence of antibodies (especially if there is a negative direct antiglobulin test). When run on the mother, this test can be negative and baby still be fatally affected in the case of some antibodies: anti-Dia, anti-Jsa, anti-Wra.

Indirect Coomb’s Test:

See indirect antiglobulin test.

Intrauterine Transfusion (IUT):

This is a life-saving procedure where a needle is inserted through the abdomen and uterus into the baby’s umbilical cord or abdomen to deliver antigen-negative blood.

Intrauterine Peritoneal Transfusion (IPT):

Injecting antigen negative red blood cells into the fetal peritoneal (abdominal) cavity. This is often used to treat babies who become anemic at very early gestations, when the umbilical vein is smaller and more difficult to access.

Intravascular Transfusion (IVT):

Injecting antigen negative red blood cells into the fetal umbilical vein to treat fetal anemia.

Intravenous Immunoglobulin (IVIG):

An infusion of mostly IgG immunoglobulins that is made by extracting the immunoglobulins from the plasma of ~1,000 donors. It is thought to lessen the mother’s antibody response and delay fetal anemia. It can also be given after birth to newborns to treat hyperbilirubinemia. It may affect the efficacy of live virus vaccines for up to a year after administration.

Iron Deficiency Anemia:

This is anemia due to iron deficiency. It most commonly affects babies around 12 months of age and is easily treated with iron supplements. This is not related to alloimmunization and hemolytic anemia.

Isoimmunization (Iso):

An older term for alloimmunization. See alloimmunization.


Jaundice:

A side effect of hyperbilirubinemia. Jaundice typically refers to the yellowing of the skin and eyes in those with hyperbilirubinemia.


Kernicterus:

A yellow staining of the brain as a result of high levels of bilirubin. Kernicterus can be a sign of bilirubin induced brain damage.

Kleihauer-Betke (KB) Test:

This test is used to See if there has been a maternal-fetal hemorrhage, and can help determine the amount of Rh Immune Globulin to administer.


Maternal Fetal Medicine (MFM):

A doctor who specializes in high risk pregnancies and complications. Sometimes called a perinatologist. The MFM is responsible for providing a care plan for you and your obstetrician (OB) or midwife to follow.

Medical Alert:

A card, bracelet, necklace, or tattoo designed to alert medical professionals to a pre-existing health condition. Alloimmunized patients are at high risk for hemolytic transfusion reactions and can carry a medical alert with wording such as “Transfusion Reaction: Anti-E Antibodies”, or “Hemolytic Transfusion Reaction Risk: Anti-K”.

Middle Cerebral Artery (MCA) Doppler Scan:

This is the name of the special ultrasound that measures how quickly the blood is flowing in the fetus’ middle cerebral artery in the brain. If the blood is flowing too quickly, doctors know the baby is likely anemic. A value of more than 1.5 times normal (called 1.5 MoMs) is considered indicative of moderate-severe anemia.

Midwife:

A person trained to assist women in childbirth. Midwives do not usually have training in alloimmunization and HDFN so they should refer patients to an MFM specialist.

Multiples of the Median (MoM):

This is the result of the calculation to see if the baby is anemic. The peak systolic velocity (PSV) and gestational age are used to calculate the MoM. A result of 1.3 indicates mild anemia. Numbers of 1.5 or higher indicate moderate to severe anemia and signals the need for an intrauterine transfusion or delivery.


Neonatal Intensive Care Unit (NICU):

This is a specialized area of the hospital where babies who need high levels of care are treated. There are four levels of neonatal care. Level I is a well newborn nursery. Level 2 is a special care nursery. Level 3 is a NICU, and level 4 is a regional NICU. Alloimmunized women should deliver at a level 3 or 4 NICU so that infants affected by HDFN can be treated immediately with phototherapy, IVIG, and if needed, exchange transfusion.

Neutropenia:

This is a reduced level of neutrophils, a specialized kind of white blood cell. HDFN can cause neutropenia. Neutropenia is often detected on a CBC. Infants with neutropenia may not be able to fight infections and extra precautions will have to be taken.

Noninvasive Prenatal Testing (NIPT):

This test is a prenatal screening done by removing some of the mother’s blood and extracting the fetal DNA found within. The fetal DNA is then analyzed in various tests. In some countries, the NIPT includes baby’s antigen status for Kell, C/c, E/e, and D. See also cffDNA.

Non-Stress Test (NST):

This is a procedure where two bands are placed on the mother’s abdomen to monitor contractions, fetal movement, and fetal heart rate. The test is usually started at 32 weeks gestation and is performed once or twice a week in an alloimmunized pregnancy. In a normal test, the baby’s heart rate should increase by 15 beats (called an “acceleration” with fetal movement in a 20 minute period of observation. This test cannot be used on its own as a reliable indicator of anemia.


Obstetrician (OB):

A doctor who specializes in pregnancy and childbirth. OBs do not usually have extensive training in alloimmunization and HDFN, so they will frequently refer patients to an MFM specialist.


Peak Systolic Velocity (PSV):

This is the measurement gained from the MCA Doppler ultrasound. It is the maximum velocity (sometimes called Pmax) that blood is moving through the middle cerebral artery. Anemic blood flows faster than nonanemic blood. The PSV is used to calculate the Multiples of the Median (MoM) value to check for anemia.

Percutaneous Umbilical Cord Blood Sampling (PUBS):

This is an older name for the procedure. Today it is more often called “cordocentesis”.

Phototherapy:

The administration of blue light with a wavelength of approximately 450nm. Phototherapy acts on the skin to change the baby's bilirubin into a water soluble form which is easier for the neonate to excrete, thus reducing the bilirubin level. The light is usually delivered with one or two banks of fluorescent lights over the baby’s bed. In some cases, “triple photherapy” can be used by placing a “biliblanket” under the baby’s back as well.

Plasmapheresis:

A procedure where the blood is removed from the mother, the antibody-rich plasma is removed, and blood cells are returned. This can decrease the antibody titer.

Preimplantation Genetic Diagnosis (PGD):

This is a test performed on embryos (from IVF) by removing one cell at the eight cell stage of development and testing the DNA. Removing only one cell at this stage in development is not harmful to the developing fetus.For alloimmunized women, this allows them to select antigen negative embryos for implantation and to avoid the risk of HDFN.

Progenitor Cells:

When used in relation to alloimmunization, progenitor cells are cells that will turn into red blood cells.


Quant:

Quants are another way to measure the antibody levels in a patient’s blood. This method is typically used in the United Kingdom. In most other countries, a titer is used. An anti-D level of > 4 iu/ml but < 15 iu/ml correlates with a moderate risk of HDFN and an anti-D level of > 15 iu/ml can cause severe HDFN. Referral for a fetal medicine opinion should therefore be made once anti-D levels are > 4 iu/ml. An anti-c level of > 7.5 iu/ml but < 20 iu/ml correlates with a moderate risk of HDFN, whereas an anti- c level of > 20 iu/ml correlates with a high risk of HDFN. Referral for a fetal medicine opinion should therefore be made once anti-c levels are > 7.5 iu/ml.


Red Blood Cell (RBC):

This is the common term for erythrocytes.

Reticulocyte count (Retic):

This is a measure of how many immature blood cells are in the bloodstream. These are future RBCs and can give an idea of how quickly a baby is making new blood to replace what the antibodies are destroying. This test is often measured every week after a baby is born, especially one that has been treated with intrauterine transfusions. It can be used to decide if a top up transfusion is needed or if another check in a couple days will suffice.

RhD Immune Globulin:

Also called Rhogam, WinRho, BayRho, and RhD prophylaxis. Rhogam is an injection of anti-D antibodies given to Rh- women. It is not a vaccine or a treatment for alloimmunization; it is a preventative only and must be given in each pregnancy. Women who already have anti-D antibodies should not receive Rhogam. Rhogam must be given within 72 hours of any bleeding, invasive procedures, and threatened or actual abortion, miscarriage, or stillbirth.

Rhesus factor (Rh):

This refers to the Rhesus D antigen that is found on red blood cells. The presence or absence of the D antigen is the + or - found on a patient’s blood type. Before the introduction of RhD immune globulin, antibody production against the D antigen was the most common presentation of alloimmunization, which is why alloimmunization is often referred to as “Rh Disease”, though many other antibodies can cause HDFN.


Sensitized:

This term refers to a woman who is already producing antibodies. When a woman has been exposed to foreign antigens and her immune system triggers a response that produces antibodies. Once antibodies have been produced, the immune system will create a memory and continue to produce them for the rest of the patient’s life.

Surrogate Pregnancy:

An embryo from one couple (created through IVF) is placed into another woman's womb to allow her to carry the pregnancy. This is sometimes an option for couples with severe alloimmunization. Placing an antigen positive embryo into another woman who does not have antibodies will result in a normal pregnancy.


Thrombocytopenia:

Thrombocytopenia is defined as a platelet count of less than 150 x 109/L. This value is the same regardless of age. Thrombocytopenia is detected with a CBC and can be a side effect of HDFN due to maternal alloimmunization. Infants with thrombocytopenia may bruise or bleed more easily.

Titer:

Titers are a reciprocal measure of the amount of antibodies in a patient’s blood. The AABB, formerly the American Association of Blood Banks, recommended changing how titers were reported to simply reflect the reciprocal value of the titer. Titer results formerly reported as 1:4, 1:8, 1:16, etc., may now be reported as 4, 8, 16, etc. If a four-fold increase is found, or if titers hit critical level (4 for Kell, 16 for all other antibodies), then MCA scans should be initiated by 18 weeks. Note: Anemia requiring IUT is possible at titers below 4 with anti-Kell. Some doctors debate if there is a critical level for anti-Kell, or if scans should be initiated regardless of titer with anti-Kell. Titers are not accurate for basing care after a previously affected pregnancy. MCA scans should be started instead.

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