Rh factor

Rh blood types

1. Yuzbasheva Nihal 221B Azerbaijan Medical University Rh FACTOR Rh Blood Types

2. Discovery The rhesus blood type named after the rhesus monkey was first discovered in 1937 by Karl Landsteiner and Alexander S. Wiener. The significance of the discovery was not immediately apparent and was only realized in 1940, after subsequent findings by Philip Levine and Rufus Stetson This serum that led to the discovery was produced by immunizing rabbits with red blood cells from a rhesus macaque. The antigen that induced this immunization was designated by them as  Rh factor   to indicate that  rhesus  blood had been used for the production of the serum.

3. When blood from humans was tested with the rabbit serum, the red blood cells of 85% of the humans tested agglutinated (clumped together). The red blood cells of the 85% (later found to be 85% of the white population and a larger percentage of blacks and Asians) contained the same factor present in rhesus monkey blood such blood was typed Rh positive. The blood of the remaining 15% lacked the factor and was typed Rh negative.  From its discovery 60 years ago, it has become second in importance only to the ABO blood group in the field of transfusion medicine. It has remained of primary importance in obstetrics, being the main cause of hemolytic disease of the newborn (HDN). In American blacks, the percentage of Rh-positives is about 95 percent, whereas in African blacks, it is virtually 100 percent.

4. Our blood types are determined by heredity. People belong to either of eight different blood types:  A Rh +, A Rh -, B Rh +, B Rh -, AB RH+, AB Rh -, 0 Rh +, or 0 Rh - . The eight blood types have different combinations of certain molecules,  antigens , on the surface of the red blood cells. The A and B antigens are sugars and the Rh antigens are proteins. The antigens expressed in the red blood cells determine an individual's blood type. Also the combination of some other molecules floating around in the blood plasma differs between the eight blood types, the so called  antibodies .

5. RH Antigens There are six common types of Rh antigens, each of which is called an Rh factor. These types are designated - C, D, E, c, d, and e. The proteins which carry the Rh antigens are  transmembrane proteins, whose structure suggest that they are ion channels. The main antigens are D, C, E, c and e, which are encoded by two adjacent gene loci, the  RHD  gene which encodes the RhD protein with the D antigen (and variants) and the  RHCE  gene which encodes the RhCE protein with the C, E, c and e antigens (and variants)

6. 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.

7. Population data for the Rh D factor and RhD neg allele:

8. Rh Immune Response When red blood cells containing 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 agglutinins 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

9. If an Rh-negative person has never before been exposed to Rh-positive blood, transfusion of Rh-positive blood into: no immediate reaction anti- Rh antibodies can develop in sufficient quantities during the next 2 to 4 weeks to cause agglutination these cells are then hemolyzed by the tissue macrophage system thus, a delayed transfusion reaction occurs, although it is usually mild subsequent 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 reaction caused by mismatched type A or B blood.

10. Rh antibodies are IgG antibodies which are acquired through exposure to Rh-positive blood (generally either through pregnancy or transfusion of blood products). The D antigen is the most immunogenic of all the non-ABO antigens. Approximately 80% of individuals who are D-negative and exposed to a single D-positive unit will produce an anti-D antibody. The percentage of alloimmunization is significantly reduced in patients who are actively  eexsanguinating . If anti-E is detected, the presence of anti-c should be strongly suspected (due to combined genetic inheritance). It is therefore common to select c-negative and E-negative blood for transfusion patients who have an anti-E. Anti-c is a common cause of delayed hemolytic transfusion reactions.

11. 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 exposure 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.

12. An Rh-negative mother having her first Rh-positive child usually does not develop sufficient anti- Rh agglutinins to cause any harm. However, about 3 percent of second Rh-positive babies exhibit some signs of erythroblastosis fetalis ; about 10 percent of third babies exhibit the disease; and the incidence rises progressively with subsequent pregnancies. 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 subsequently hemolyze , releasing hemoglobin into the blood.

13. 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. The jaundiced, erythroblastotic newborn baby is usually anemic at birth 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.

14. 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 circulatory 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 .

15. The New York Times’s first mention of the Rh factor, on Sunday, March 26, 1944, should have made bigger news than it did — in a brief article at the bottom of the “Science in Review” column on Page 9 of Section 4, The News of the Week in Review. “The recently discovered Rh factor in human blood,” it said, “need not cause infant deaths and childless marriages.” The article quoted Dr. Alexander S. Wiener, who in 1940, along with his colleague Karl Landsteiner, first described the Rh factor in humans. “Dr. Wiener believes that some method may be developed to desensitize mother so that their babies may be saved,” the article said. “Research based on this hope has already been started.” It was not until Sept. 11, 1965, that the paper reported on clinical trials of a drug treatment for Rh disease. this was the first test of Rh immune globulin, a solution of antibodies derived from human plasma. Injected into the Rh-negative mother, the antibodies bind to and destroy fetal Rh-positive blood cells that have passed from the fetus to the mother during birth .

16. In the 1970s, a dramatic reduction in the incidence of erythroblastosis fetalis was achieved with the development of Rh immunoglobulin globin , an anti-D antibody that is administered to the 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 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 r esponse to the D antigen.   Coombs test  (also known as  Coombs' test ,  antiglobulin test  or  AGT ) is either of two clinical blood tests used in  immunohematology   and immunology. The two Coombs tests are the  direct Coombs test   and the  indirect Coombs test   The indirect Coombs test is used to screen for antibodies in the preparation of  bloodmfor  blood transfusion. The donor's and recipient's blood must be ABO and Rh D compatible. Donor blood for transfusion is also screened for infections in separate processes

17. Inheritence The Rh factor genetic information is also inherited from our parents, but it is inherited independently of the ABO blood type alleles. Someone who is " Rh positive" or " Rh +" has at least one Rh + allele, but could have two. Their genotype could be either Rh +/ Rh + or Rh +/ Rh -. Someone who Rh - has a genotype of Rh -/ Rh -. Just like the ABO alleles, each biological parent donates one of their two Rh alleles to their child.

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