SESSION13: Rh INCOMPATABILITY

Blood is made of several kinds of cells and materials. For example, red blood cells carry oxygen to body cells for cellular respiration. The liquid part of the blood carries molecules (called antibodies) that help defend the body against foreign invaders such as bacteria And not all blood is the same. The differences in human blood are due to the presence of absence of certain protein molecules on the surface of red blood cells. If a person does not have these proteins in their blood, they may make antibody molecules to attack them. If you receive a blood transfusion, you must receive blood that is compatible to yours. If blood from different groups is mixed together, the antibodies make the red blood cells stick together. Large clots form and can block blood vessels. Death can occur. Blood Types: Using the ABO blood classification system, every human being belongs to one of four blood types : A, B, AB, or O. These four blood types are determined genetically by three possible alleles (IA, IB, and i). Of course, each of us only gets two alleles (one from each parent) but with these multiple alleles, there are more than two phenotypes.

Rh Factor During the 1940s, scientists discovered that when red blood cells (RBCs) from rhesus monkeys were injected into rabbits they produced an antiserum that, when injected back into the monkeys caused agglutination (clumping) of some RBCs. The agglutination RBCs contained the rhesus (Rh) antigen (the substance that stimulates production of antibodies) and was designated Rh negative. Subsequent research revealed that the Rh factor is not a single antigen but a complex blood system with a number of variants. The Six common Rh antigens are identified as C, D, E , c , d , & e . Antibody formation results from the presence of one or more of these antigens. However, d is not a true antigen and does not induce antibody formation. Because 23 pairs of homologous chromosome one set from each parent are present in each cell, an individual's genetic constitution in terms of these antigens might be. The degree to which each antigen will induce antibody formation known as antigenicity potency varies. No specific antiserum (serum that contains antibodies specific for the antigen) has been found for d; therefore, d is used to represent the absence of a discernable antibody. Hemolytic Disease of the Newborn ( HDNB) Hemolytic Disease of the Newborn is also called erythroblastosis fetalis. This condition occurs when there is an incompatibility between the blood types of the mother and baby. RBCs of the fetus and newborn are destroyed by all types of IgG antibody from the mother which can cross the placenta. The Result is erythroblastosis fetalis (HDNB) due to the marked NRBCS in fetus blood , eryhthroblastic response to the hemolytic anemia in the fetus . At least 0.5 mL of fetal blood is necessary to produce alloimmunization. Although the placenta separates the cellular components of the maternal and fetal circulation, some transplacental bleeding occurs during delivery. -Bleeding may also occur during Pregnancy because of trauma or a defect in the membranes. The mother is thus exposed to the foreign antigens of her baby and her immune system has the potential to respond to those antigens that she lacks. The more babies and deliveries, the greater the risk of immunological response. Actually, most mothers do not react to most of the antigens to which they are exposed. Some antigens are weak and do not stimulate the immune system.

The response potential is also dependent on the amount of blood that passes from fetus to mother. -The Severity of the disease varied from mild, self limiting anemia to severe conditions manifested by cardiac failure , pulmonary congestion , edema ( hydrops fetalis ) , and systemic pathology . - Fetal RBCs coated with maternal are removed from the circulation by extravascular hemolysis, so increase destruction stimulate fetal hematopoietic tissue to increase. Erythrocyte production in bone marrow and extramedullary production also occur, lead to hepatosplenomegaly, so fetus may not be able to compensate, anemia result. - The other major problem is the accumulation of bilirubin in the neonate's tissues as RBCs destruction continues. Without the support of the mother's liver, the unconjugated bilirubin (in utero it crosses the placenta) is deposited in the central nervous tissue (in the brain) a condition called Kernicterus. The damage is irreversible due to poorly developed the enzyme glucorony transferase , producing mental retardation or death ( after birth ). - Thus the prenatal problem is one of anemia and postnatal problem is one of bilirubin accumulation. Laboratory findings: Anemia (new born): mild ( Hb = 13 g/dl ) or severe ( Hb = 8 g / dl ). Reticulocytosis , NRBCs Leukocytosis Spherocytes, numerous in ABO HDNB. Bilirubinemia. Positive coombs test, (direct antiglobulin) on cord blood cells (detect Abs in the mother's serum that react with RBCs of the infant.

Causes Factors that influence an Rh-negative pregnant female's chances of developing Rh incompatibility include the following:

Ectopic pregnancy Placenta previa Placental abruption Abdominal/pelvic trauma In utero fetal death Any invasive obstetric procedure (eg, amniocentesis) Lack of prenatal care

Spontaneous abortion

Management: The Most common and severe forms of HDN were to Rh Incompatibility (D antigen). Now Rh immune globulin ( Rh Ig )is given antenatally ( 28 weeks of gestation ) and / or within 72 hrs after delivery . The Rh Ig binds the Circulating fetal cells and enhances their removal by the spleen, but without stimulating the immune response. Rh Ig must be given with each incompatible pregnancy and it is of no use if an anti D titer has already developed. Because of these preventive measures, this type of HDN is now decreased to 1/3 of the cases. Assessment and treatment after delivery Cord blood samples must be taken to check the baby's Haemoglobin, bilirubin and Direct Antiglobulin Test (DAT) to check if the baby's red cells are coated with maternal anti-D antibodies. If mild HDN then the baby may need phototherapy only to reduce the level of bilirubin in the blood. If severe HDN then the baby will need blood exchange transfusion which replaces the babys blood with transfused blood, removing harmful bilirubin and anti-D antibody, while at the same time treating the anemia. Anti-D (also known as Rho (D) immune globulin intravenous or anti-D IGIV) is a blood product consisting of antibodies to the RH factor on red blood cells. Following a treatment with anti-D, the patient's RH positive red blood cells link to the anti-D antibodies and the anti-body coated red blood cells are then removed in the spleen. Since red blood cells are eliminated, the process often causes a mild anemia. However, it is usually successful in keeping the antibody-coated platelets of the ITP patient in circulation. For the product to be safe and effective, the patient must be RH positive, have a spleen, and not be anemic or deficient in IgA. Anti-D is made from human plasma derived from a limited list of donors in a special program that stimulates the production of high levels of antibodies. The antibodies from the donors are combined in batches that undergo a viral inactivation and micro filtration process using solvent/detergent to remove or deactivate diseasecausing agents that can be transmitted through blood infusions Dosage

According to the package insert, the suggested dosing is 50 mcg/kg of bodyweight although some clinical studies report greater success at a 75 mcg/kg dose.3 because the antibodies are concentrated, a treatment with antiD requires less product and a shorter infusion time than IVIg. Premedication with paracetamol / acetaminophen, or corticosteroids is advised to reduce the risk of fever and chills. Side Effects Side effects developed following 7% of infusions, and included headaches, chills, fever and body aches. A remote risk of anaphylaxis (shock response) exists for patients with hypersensitivity to blood products. A very small number of people receiving anti-D experience intravascular hemolysis, the destruction of red blood cells in circulation. This type of red cell destruction can cause anemia, multi-system organ failure, difficulty breathing, and even death. Patients should immediately report symptoms of back pain, shaking chills, fever, discolored urine, decreased urine output, sudden weight gain, fluid retention/edema and/or shortness of breath to their physicians. Anti-D can interfere with the efficacy of live virus vaccines, therefore the manufacturers do not recommend live virus immunizations within three months after an anti-D treatment.

Treatment and manegment: Cord blood samples must be taken to check the baby' haemoglobin, bilirubin and Direct Antiglobulin Test (DAT) to check if the baby's red cells are coated with maternal anti-D antibodies. If mild HDN then the baby may need phototherapy only to reduce the level of bilirubin in the blood. If severe HDN then the baby will need exchange transfusion which replaces the babys blood with transfused blood, removing harmful bilirubin and anti-D antibody, while at the same time treating the anaemia. Phototherapy:

When a newborn infant has an elevated bilirubin level (the infant is jaundiced), there is bilirubin present in the circulation, in the small capillaries in the skin and in the skin and subcutaneous tissues, shining light on the skin, it penetrates the skin and also the subcutaneous tissues and converts the bilirubin that is present to other forms of bilirubin called photobilirubin and lumirubin. These are isomers of the bilirubin molecule (they have the same molecular formula but it has been rearranged). Bilirubin forms every day from the breakdown of our red blood cells and this occurs in babies as well. The difference is that the newborn infant's liver is not capable of conjugating and excreting the bilirubin as well as an adult. Conjugation is required before the bilirubin can be excreted. This is one of the reasons why most newborn infants are jaundiced. When bilirubin is converted to these isomers, they can be removed from the body without requiring conjugation in the liver.