Rh Blood Types
Along with the O-A-B blood type system, the Rh blood type system is also important when transfusing blood. The major difference between the O-A-B system and the Rh system is the following: In the O-A-B system, the plasma agglutinins responsible for causing transfusion reactions develop spontaneously, whereas in the Rh system, spontaneous agglutinins almost never occur. Instead, the person must first be massively exposed to an Rh antigen, such as by trans-fusion of blood containing the Rh antigen, before enough agglutinins to cause a significant transfusion reaction will develop.
There are six common types of Rh antigens, each of which is called an Rh factor. These types are desig-nated C, D, E, c, d, and e. A person who has a C antigen does not have the c antigen, but the person missing the C antigen always has the c antigen. The same is true for the D-d and E-e antigens. Also, because of the manner of inheritance of these factors, each person has one of each of the three pairs of antigens.
The type D antigen is widely prevalent in the population and considerably more antigenic than the other Rh antigens. Anyone who has this type of antigen is said to be Rh positive, whereas a person who does not have type D antigen is said to be Rh negative. However, it must be noted that even in Rh-negative people, some of the other Rh antigens can still cause transfusion reactions, although the reactions are usually much milder.
About 85 per cent of all white people are Rh posi-tive and 15 per cent, Rh negative. In American blacks, the percentage of Rh-positives is about 95, whereas in African blacks, it is virtually 100 per cent.
Formation of Anti-Rh Agglutinins. When red blood cellscontaining Rh factor are injected into a person whose blood does not contain the Rh factor—that is, into an Rh-negative person—anti-Rh agglutinins develop slowly, reaching maximum concentration of agglu-tinins about 2 to 4 months later. This immune response occurs to a much greater extent in some people than in others. With multiple exposures to the Rh factor, an Rh-negative person eventually becomes strongly “sensitized” to Rh factor.
Characteristics of Rh Transfusion Reactions. If an Rh-negative person has never before been exposed to Rh-positive blood, transfusion of Rh-positive blood into that person will likely cause no immediate reaction. However, anti-Rh antibodies can develop in sufficient quantities during the next 2 to 4 weeks to cause agglu-tination of those transfused cells that are still circulat-ing in the blood. These cells are then hemolyzed by the tissue macrophage system. Thus, a delayed transfusion reaction occurs, although it is usually mild. On subse-quent transfusion of Rh-positive blood into the same person, who is now already immunized against the Rh factor, the transfusion reaction is greatly enhanced and can be immediate and as severe as a transfusion reac-tion caused by mismatched type A or B blood.
Erythroblastosis Fetalis (“Hemolytic Disease of the Newborn”)
Erythroblastosis fetalis is a disease of the fetus and newborn child characterized by agglutination and phagocytosis of the fetus’s red blood cells. In most instances of erythroblastosis fetalis, the mother is Rh negative and the father Rh positive. The baby has inherited the Rh-positive antigen from the father, and the mother develops anti-Rh agglutinins from expo-sure to the fetus’s Rh antigen. In turn, the mother’s agglutinins diffuse through the placenta into the fetus and cause red blood cell agglutination.
Incidence of the Disease. An Rh-negative mother havingher first Rh-positive child usually does not develop sufficient anti-Rh agglutinins to cause any harm. However, about 3 per cent of second Rh-positive babies exhibit some signs of erythroblastosis fetalis; about 10 per cent of third babies exhibit the disease; and the incidence rises progressively with subsequent pregnancies.
Effect of the Mother’s Antibodies on the Fetus. After anti-Rh antibodies have formed in the mother, they diffuse slowly through the placental membrane into the fetus’s blood. There they cause agglutination of the fetus’s blood. The agglutinated red blood cells subse-quently hemolyze, releasing hemoglobin into the blood. The fetus’s macrophages then convert the hemoglobin into bilirubin, which causes the baby’s skin to become yellow (jaundiced). The antibodies can also attack and damage other cells of the body.
Clinical Picture of Erythroblastosis. The jaundiced, ery-throblastotic newborn baby is usually anemic at birth, and the anti-Rh agglutinins from the mother usually circulate in the infant’s blood for another 1 to 2 months after birth, destroying more and more red blood cells.
The hematopoietic tissues of the infant attempt to replace the hemolyzed red blood cells. The liver and spleen become greatly enlarged and produce red blood cells in the same manner that they normally do during the middle of gestation. Because of the rapid production of red cells, many early forms of red blood cells, including many nucleated blastic forms, are passed from the baby’s bone marrow into the circula-tory system, and it is because of the presence of these nucleated blastic red blood cells that the disease is called erythroblastosis fetalis.
Although the severe anemia of erythroblastosis fetalis is usually the cause of death, many children who barely survive the anemia exhibit permanent mental impairment or damage to motor areas of the brain because of precipitation of bilirubin in the neuronal cells, causing destruction of many, a condition called kernicterus.
Treatment of the Erythroblastotic Neonate. One treatmentfor erythroblastosis fetalis is to replace the neonate’s blood with Rh-negative blood. About 400 milliliters of Rh-negative blood is infused over a period of 1.5 or more hours while the neonate’s own Rh-positive blood is being removed. This procedure may be repeated several times during the first few weeks of life, mainly to keep the bilirubin level low and thereby prevent kernicterus. By the time these transfused Rh-negative cells are replaced with the infant’s own Rh-positive cells, a process that requires 6 or more weeks, the anti-Rh agglutinins that had come from the mother will have been destroyed.
Prevention of Erythroblastosis Fetalis. The D antigen ofthe Rh blood group system is the primary culprit in causing immunization of an Rh-negative mother to an Rh-positive fetus. In the 1970’s, a dramatic reduc-tion in the incidence of erythroblastosis fetalis was achieved with the development of Rh immunoglobu-lin globin, an anti-D antibody that is administered tothe expectant mother starting at 28 to 30 weeks of gestation. The anti-D antibody is also administered to Rh-negative women who deliver Rh-positive babies to prevent sensitization of the mothers to the D antigen. This greatly reduces the risk of developing large amounts of D antibodies during the second pregnancy.
The mechanism by which Rh immunoglobulin globin prevents sensitization of the D antigen is not completely understood, but one effect of the anti-D antibody is to inhibit antigen-induced B lymphocyte antibody production in the expectant mother. The administered anti-D antibody also attaches to D-antigen sites on Rh-positive fetal red blood cells that may cross the placenta and enter the circulation of the expectant mother, thereby interfering with the immune response to the D antigen.
If donor blood of one blood type is transfused into a recipient who has another blood type, a transfusion reaction is likely to occur in which the red blood cells of the donor blood are agglutinated. It is rare that thetransfused blood causes agglutination of the recipient’scells, for the following reason: The plasma portion ofthe donor blood immediately becomes diluted by all the plasma of the recipient, thereby decreasing the titer of the infused agglutinins to a level usually too low to cause agglutination. Conversely, the small amount of infused blood does not significantly dilute the agglutinins in the recipient’s plasma. Therefore, the recipient’s agglutinins can still agglutinate the mis-matched donor cells.
As explained earlier, all transfusion reactions even-tually cause either immediate hemolysis resulting from hemolysins or later hemolysis resulting from phagocy-tosis of agglutinated cells. The hemoglobin released from the red cells is then converted by the phagocytes into bilirubin and later excreted in the bile by the liver.The concentration of biliru-bin in the body fluids often rises high enough to cause jaundice—that is, the person’s internal tissues and skinbecome colored with yellow bile pigment. But if liver function is normal, the bile pigment will be excreted into the intestines by way of the liver bile, so that jaun-dice usually does not appear in an adult person unless more than 400 milliliters of blood is hemolyzed in less than a day.
Acute Kidney Shutdown After Transfusion Reactions. One ofthe most lethal effects of transfusion reactions is kidney failure, which can begin within a few minutesto few hours and continue until the person dies of renal failure.
The kidney shutdown seems to result from three causes: First, the antigen-antibody reaction of the transfusion reaction releases toxic substances from the hemolyzing blood that cause powerful renal vasocon-striction. Second, loss of circulating red cells in the recipient, along with production of toxic substances from the hemolyzed cells and from the immune reac-tion, often causes circulatory shock. The arterial blood pressure falls very low, and renal blood flow and urine output decrease. Third, if the total amount of free hemoglobin released into the circulating blood is greater than the quantity that can bind with “hapto-globin” (a plasma protein that binds small amounts of hemoglobin), much of the excess leaks through the glomerular membranes into the kidney tubules. If this amount is still slight, it can be reabsorbed through the tubular epithelium into the blood and will cause no harm; if it is great, then only a small percentage is reab-sorbed. Yet water continues to be reabsorbed, causing the tubular hemoglobin concentration to rise so high that the hemoglobin precipitates and blocks many of the kidney tubules. Thus, renal vasoconstriction, circu-latory shock, and renal tubular blockage together cause acute renal shutdown. If the shutdown is com-plete and fails to resolve, the patient dies within a week to 12 days, unless treated with an artificial kidney.