Hemolytic Disease of the Newborn - Essay Example

Running head: Hemolytic Disease of the Newborn Hemolytic Disease of the Newborn [The of the appears here] [The of institution appears here] 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. "hemolytic" means breaking down of red blood cells "erythroblastosis" refers to making of immature red blood cells "fetalis" refers to fetus HDN most frequently occurs when an Rh negative mother has a baby with an Rh positive father. When the baby's Rh factor is positive, like the father's, problems can develop if the baby's red blood cells cross to the Rh negative mother. This usually happens at delivery when the placenta detaches. However, it may also happen anytime blood cells of the two circulations mix, such as during a miscarriage or abortion, with a fall, or during an invasive prenatal testing procedure (i.e., an amniocentesis or chorionic villus sampling). (Vucinovic M, Jadric H, Karelovic D, Roje D, Haspl-Hundric Z, Hrgovic Z, Vucinovic Z, 2004). The mother's immune system sees the baby's Rh positive red blood cells as "foreign." Just as when bacteria invade the body, the immune system responds by developing antibodies to fight and destroy these foreign cells. The mother's immune system then keeps the antibodies in case the foreign cells appear again, even in a future pregnancy. The mother is now "Rh sensitized." Although it is not as common, a similar problem of incompatibility may happen between the blood types (A, B, O, AB) of the mother and baby in the following situations: Mother's Blood Type O A B Baby's Blood Type A or B B A In a first pregnancy, Rh sensitization is not likely. Usually it only becomes a problem in a future pregnancy with another Rh positive baby. During that pregnancy, the mother's antibodies cross the placenta to fight the Rh positive cells in the baby's body. As the antibodies destroy the red blood cells, the baby can become sick. This is called erythroblastosis fetalis during pregnancy. In the newborn, the condition is called hemolytic disease of the newborn. (Vucinovic M, Jadric H, Karelovic D, Roje D, Haspl-Hundric Z, Hrgovic Z, Vucinovic Z, 2004). Hemolytic disease of the newborn (HDN) occurs due to maternal IgG antibodies crossing the placenta thereby producing hemolysis mainly due to Rh, ABO and Kell groups. A systematic approach to the Rh HDN involves an obstetric history of previous isoimmunized baby, timing and regular monitoring of maternal Rh antibodies and pigment assay of amniotic fluid. Timely decision regarding in utero transfusion and early termination of pregnancy based on the maternal monitoring has radically improved the outcome of these babies. Antenatal prophylaxis with anti D has resulted in great reduction in the magnitude of Rh problem. The fetal blood sampling and in-utero intravenous transfusions has made it possible for almost 100% survival of isoimmunized pregnancies without hydrops. Alternative methods--IVIG and plasma exchange are still of limited application. ABO HDN though common is not a serious form of disease and dose not warrants invasive antenatal monitoring. Anti-Kell is found in patients having received multiple transfusions and the rapid progress of hemolysis in them may not allow such systematic follow up as in Rh HDN. (Narang A, Jain N, 2001). Antibodies are produced by B lymphocytes. Maturation culminates with migration of the B cells to the reticulo-endothelial tissues of the body including the lymph nodes and parts of the spleen, bone marrow, liver, gastrointestinal tract and other tissues. Antibodies are a miscellaneous mixture of serum globulins and share the ability to bind individually to specific antigens. Those serum globulins with antibody activity are known as immunoglobulins (Ig). All immunoglobulin molecules have common structural features. The part of the molecule that binds to the corresponding antigen is different in each immunoglobulin. The basic structure of an immunoglobulin consists of two identical light (L) chains and two identical heavy (H) chains. A disulfide bridge (S-S) links each light chain to a heavy chain, and another disulfide bridge (S-S) bonds the two heavy chains. (Carmelina Cuschieri, 1993). There are two types of light chains, kappa () and lambda (), and five main types of heavy chains; gamma (), meu (), alpha (), delta () and epsilon (). Each heavy chain corresponds to the different immunoglobulin class namely, Ig G, Ig M, Ig A, Ig D and Ig E respectively. Each has several unique biological properties. Ig G is the only immunoglobulin that crosses the placenta, and Ig M is a greatly effective antibody since it can make other serum constituents active to cause lysis of bacteria. Ig A is considered to be a secretory immunoglobulin, Ig D is found on lymphocytes at certain stages of development, and Ig E binds with high affinity to mast cells and it is mainly involved in allergies. (Carmelina Cuschieri, 1993). In selecting donor blood for transfusion, testing of each recipient's red cells for the presence or absence of the Rh (D) antigen, started to become indispensable in the 1940's. Though at first restricted by the limited availability of the necessary reagent, D grouping has become as much a part of the pretransfusion routine as ABO grouping. The red cells of donors are also always tested for the D antigen (and for the weak D variant), so that the units are suitably labelled and classified as 'Rh positive' or 'Rh negative'. The antigens of the Rhesus system As the Fisher-Race theory states, there are three pairs of allelic genes: C and c, D and d, E and e. They occupy three loci on chromosome 1, are closely linked and are inherited as triplets. Each triplet contains one gene from each pair. Rhesus antigens are considered to be proteins, still they require phospholipids for expression. It has been customarily considered that the so called silent gene d is present in the triplet when the D antigen is absent. A person who has the D antigen is said to be Rh 'positive', and conversely a person who lacks it is Rh 'negative'. On the other hand, the Wiener theory assumes that the whole expression of the Rhesus system is controlled by a series of genes each occupying only one locus on the chromosome. The Wiener notation employs symbols for the description of the Rh phenotype. (Carmelina Cuschieri, 1993). A third terminology suggested by Rosenfield, was established to define the reactions of the specific antisera against which the particular sample was tested. This gave a precise description of the Rhesus status. Rhesus negative cells could only be shown as cde, rh or r by the Fisher-Race and Wiener notations whereas, according to Rosenfield's terminology, they would be labelled as Rh: -1, -2, and -3 when tested only against anti-D, anti-C and anti-E, or as Rh: -1, -2, -3, 4 and 5 if tested against anti-D, anti-C, anti-E, anti-c and anti-e. It must be said that among the rarer Rhesus antigens, some have been termed according to Fisher, others according to Wiener, but all were consequently given a Rosenfield number. Du antigen and D variants The Du antigen is a weak form of the D antigen. When it is tested with several anti-D antisera, some will agglutinate Du red cells, whereas others will not do so. A blood donor who has Du antigens, must be grouped as Rh (D) positive. If they are blood receivers, they can be transfused safely with Rh (D) positive blood. However, to eliminate any risk of transfusion reactions, whether the phenotype is Du or Rh (D) negative, Rh (D) negative blood should be transfused. Likewise, pregnant women with the Du antigen, do not need the administration of anti-Rh (D) immunoglobulin unless there is doubt as to whether the phenotype is Rh (D) or Du negative. Anti-D is rarely produced in subjects with D variants. D variants lack one or more epitopes of the D antigen. Certain examples of Du are the result of Cde being situated on a normal D gene in the opposite gene complex. The C gene on the same gene complex may also weaken the expression of the D antigen. There are other D antigens known as partial D. These red cells lack an epitope or epitopes of the normal D antigen. Individuals with such a D antigen can thus form anti-D that is specific to the missing epitopes. The Du antigen varies from the D antigen quantitatively in a sense that Du has a decreased number of antigen sites per red cell. (Carmelina Cuschieri, 1993). It is also important to identify the genotype of the father in the case of an Rh immunized mother in order to assess the chances of a Rhesus-positive foetus. Unfortunately, however, the presence of either DD or Dd can only be determined from known frequencies of certain genotypes in large populations. The other part of the phenotype can be established from the results of the tests using anti-D, anti-C, anti-E, anti-c and anti-e. Such studies have been carried out in Caucasians, in which case if the phenotype is, say CCDee, the most likely genotype is CDe/CDe; or if the phenotype is cCDee, then the genotype is probably CDe/cde. Rarely red cells can lack one or more Rhesus antigens. This condition is known as Rhnull and it is a rare genotype characterised by complete absence of all Rh antigens. Rhnull is sometimes associated with congenital haemolytic anaemia. The antibodies of the Rhesus system The antibodies of the Rhesus system are all immune, except for some naturally occurring anti-E antibodies. Anti-D is the most significant Rhesus antibody. It is always immune and causes both haemolytic disease of the newborn and haemolytic transfusion reactions. Anti-D antibodies are usually detected by the indirect antiglobulin test, and do not bind complement. Anti-C may be found together with anti-D antibodies. (Carmelina Cuschieri, 1993). Anti-c is the second most important antibody in the Rhesus system. It can cause immediate and delayed transfusion reactions as well as haemolytic disease of the newborn. Other Rhesus antibodies are anti-Cw, anti-E and anti-e. They are less common than anti-c and anti-D but similarly can cause serious clinical problems. When a Rhesus antigen is introduced in the body, through transfusion or pregnancy, a corresponding Rhesus antibody is formed in response to it, but the degree of response varies widely. It has been shown that some Rhesus negative people (about 30 percent), known as non-responders, fail to produce anti-D in spite of repeated injections with Rhesus positive blood. Those persons who produce anti-D after several injections will have low titre levels, while those responding after a single injection of Rhesus positive blood generally acquire high titres. It was also noted that those who respond to a low dose initially, often fail to respond to a high dose later, and vice versa. A similar situation occurs during pregnancy. Some Rhesus negative mothers may give birth to several Rhesus positive newborns without forming anti-D, while others become immunized at the end of the first or second pregnancy. Non-responders may not produce anti-D even though during pregnancy, there was substantial foetal bleeds. Once formed, anti-D tends to persevere and increase in subsequent Rhesus positive pregnancies. However, in each case the titre eventually stabilizes at a characteristic level. If this titre level is moderate, say 1:256 tested by the indirect antiglobulin test, even though at first it rises to 1:2000, it has been noticed that in a second pregnancy, it returns to 1:128 - 1:256 and remains at this latter level. Briefly, it can be said that anti-D titre levels increase with each new stimulus, but there are many exceptions to this rule. (Carmelina Cuschieri, 1993). Reference: Carmelina Cuschieri (1993). RHESUS-HAEMOLYTIC DISEASE OF THE NEWBORN WITH REFERENCE TO ANTI-D A special project submitted in partial fulfillment of the requirements for the diploma of Health Science Medical Laboratory Science Narang A, Jain N (2001). Haemolytic disease of newborn; Neonatal Division, Dept. of Pediatrics, PGIMER, Sector 12, Chandigarh., Volume : 68 Vucinovic M, Jadric H, Karelovic D, Roje D, Haspl-Hundric Z, Hrgovic Z, Vucinovic Z.(2004). [Haemolytic disease of the newborn--from a mother with anti-Kell, anti-E and anti-Vel anti-erythrocyte alloantibodies] Z Geburtshilfe Neonatol. 2004 Oct; 208(5):197-202. Read More