RH Disease and Red Blood Cell Alloimmunization (Isoimmunization)

When your body is exposed to germs or cells that are different from your own body's normal healthy tissues, your body forms a substance called antibody (immunoglobulin) against  areas on the foreign cells  that are different from  your own cells called antigens (antibody generator). Antibodies attach to the antigens and  destroy the invader directly , or label them for removal by your  white blood cells. The  first response by your body to the unfamiliar foreign  antigen is called sensitization and your body is now prepared  to recognize and respond with greater force on the next  encounter with this same unwanted intruder. 

The surface of your red blood cells is also covered by different antigens that you have inherited from each of your parents . Red blood cells may be identified as different types and separated into groups based on the presence or absence of the antigens on the red blood cell's surface.  There are thirty major blood group systems currently recognized including the  ABO , Rh (Rhesus) , Kell ,Duffy (Fya), Kidd (Jka), MNS blood group systems . If your baby inherits a blood type from the father that is different from  your own  blood type you may become sensitized to the baby's blood type and produce antibodies against the baby's red blood cells. Antibodies may be produced in five different forms. Immunoglobulin M (IgM) , and immunoglobulin G (IgG) are the forms found in the greatest amounts in your blood . IgG is the only form of antibody that can cross the placenta into the baby's blood .Women  most often become sensitized to a blood type different from their own  during a pregnancy or after a blood transfusion.  The formation of antibodies against an antigen from another human being is called alloimmunization or isoimmunization.

Hemolytic Disease of the Fetus and Newborn (HDFN)
I
f a mother has antibodies against the blood type of a baby she is carrying , the mother's antibodies may cross into the baby's blood and attach to the baby's red blood cells causing destruction of the red blood cells (hemolysis) and lead  to anemia in the baby. This condition is called hemolytic disease of the fetus and newborn (HDFN) . The anemia may be severe enough to cause heart failure (hydrops) or death in the baby. HDFN is most commonly caused by a mother who does not have the D antigen on her red blood cells (Rh negative) producing antibodies against the blood of her baby that has the D antigen on its red blood cells (Rh positive)

Screening for Blood Antibodies
Testing for blood antibodies is part of usual prenatal care. Sometimes an antibody will be found in too small of an amount to identify, and you will need to have your blood tested at regular intervals . Once identified , the level of the antibody in your blood is measured and reported as a number called a titer. A low titer number means there is a small amount of the antibody in your blood. A higher titer number means you have a larger amount of the antibody in your blood. As the amount of antibody in your blood increases the chances that your baby will have severe anemia also increases . The antibody level that severe anemia and fetal hydrops is more likely to occur is called the "critical" titer and in most centers this level is between 8 and 32.

The following antibodies do not usually cause HDFN [1-3)

Lewis (Anti-Lea, Anti-Leb ), anti-P1, anti-I, anti-N, anti-M , and cold antibodies (antibodies that react below body temperature , 37 degrees C)  are usually IgM antibodies that cannot cross the placenta and would not be expected to cause HDFN. some   naturally occurring since they appear without previous exposure to antigen However some of these antibodies such as anti-M may also be present in the  IgG form than can cross the placenta and potentially cause HDFN. If anti-M, IgG optimally reactive at 37 degrees C, is identified in the mother's blood, the father's blood must be checked for the presence of the M antigen.

The following antibodies may produce mild to severe HDFN. ACOG recommends fetal assessment  [1]

Rh (anti-D, anti-E, anti-c ), Kell (anti--K), Duffy (anti-Fya)  Kidd (anti--Jka), MNS (anti-M, anti-S, anti-s , anti--U, anti-Mia, anti-Mta) , Diego (anti-D1a, anti-Dib) , P (anti-P1PK also known as anti-TJa)- may cause severe HD Public antigen (anti-Yta, anti-Ena, anti-COa), Private antigens (anti-Biles, anti-Good, anti-Heibel, anti-Radin, anti-Wrighta, anti-Zd)

Rh (anti-D, anti-E, anti-c ), Kell (anti--K), Duffy (anti-Fya) antibodies are the most likely to cause HDFN requiring intrauterine transfusion.

If you have an antibody that could cause severe anemia in your baby, then the red blood cells of the father should be tested for the matching antigen to the antibody. If the father does not have the antigen on his blood cells then the baby will not have the antigen either.  if the father has the antigen, then the baby should also be tested to see if it has inherited the father's red blood cell antigen.

Monitoring

  • Except in cases of alloimmunization due to anti-Kell antibodies (and possibly anti-M IgG antibodies) , red cell antibodies in pregnancy are managed in a similar fashion.

  • Antibody titers are not used for monitoring Kell-sensitized patients because Kell antibodies levels do not predict the well being of the baby. Kell sensitized pregnancies may be followed using ultrasound as for a woman with a previously affected pregnancy.

  • Recommendations on the management of patients with anti-M IgG differ, some authorities recommend in women with a first sensitized pregnancy have levels of the antibody measured as for other blood antibodies if the first titer is greater than 4. Others suggest that serial antibody titers are not reliable, and the that pregnancies with anti-M IgG should be monitoring as Kell-sensitized pregnancies are.

Monitoring a First Sensitized Pregnancy [1,4,5]

  • If this is the first pregnancy that you have had with a positive blood antibody (and you do not have anti-Kell or anti-M antibodies) the level of the antibody in your blood will be measured  every month until about
    24 weeks  and then every 2 weeks thereafter. If the titer remains under less than or equal to 16  the critical value you may deliver at term.

    • If the titer is more than 16 an ultrasound machine will be used to see if your baby is developing anemia by  measuring the speed of the blood flowing through a blood vessel in your baby's brain called
      the middle cerebral artery. The measurements are started at about 18 weeks and are repeated every 1 to 2 weeks.

    • If the flow of the blood becomes  faster than the expected flow for your baby's age (1.5 MoM) , severe anemia is more likely and you may be referred for blood transfusion of the baby while it is still in the womb.

    • Antenatal testing is started at 32 weeks and delivery at 37 to 38 weeks is recommended.

Monitoring in a Woman with a Previously Affected Pregnancy [1, 3,6]

  • If you have had a previous pregnancy with stillbirth related to HDFN ,  fetal hydrops, intrauterine fetal transfusion, preterm delivery because of fetal anemia, or neonatal exchange transfusion  ultrasound will be used to see if your baby is developing anemia by  measuring the speed of the blood flowing through  your baby's brain starting at about 16 to 18 weeks. The measurements  and are repeated every 1 to 2 weeks.

  • If the flow of the blood becomes  faster than the expected flow for your baby's age (1.5 MoM) , severe anemia is more likely and you may be referred for blood transfusion of the baby while it is still in the womb.

  • Antenatal testing is started at 32 weeks and delivery at 37 to 38 weeks is recommended.

MORE INFORMATION AND REFERENCES :http://www.obfocus.com/high-risk/Rh_disease/RH%20Disease%20And%20Isoimmunization.htm
Copyright 2014 by Focus Information Technology. All rights reserved.