Medical brain notes 30

  TRANSFUSIONANDTRANSPLANTATION INTRODUCTION Blood transfusion is the transfer of blood or blood products into the blood-stream of a patient who has lost blood due to injury, disease or an operation. The amount and type of blood or component transfused depends on the needs of the patient. Transfusions of blood and blood products are routine and are generally safe therapeutic procedures that are rarely associated with adverse reactions. However, it is only in the last hundred or so years that the foundations of these procedures have been established. Similarly, the transplantation of organs and solid tissues from one individual to another to replace diseased or nonfunctional tissue is now well established. However, it is little more than 50 years since the first successful clinical transplant of a kidney in 1954 paved the way for the range of tissue transplants cur-rently available. Advances in the transplantation of bone marrow and stem cells have brought the two fields of transfus...

  BLOOD AND BLOOD PRODUCTS FOR TRANSFUSION The role of the biomedical scientist in the transfusion laboratory is to ensure that the blood and blood products being transfused into a patient are safe. To ensure safety, the blood is tested to determine its blood group and to check that it is not contaminated with harmful microorganisms. In addition, checks are made to ensure that the transfused blood does not contain anti-bodies that will destroy the erythrocytes of the recipient and cause death. Blood transfusions are required to replace blood lost as a result of accident or surgery. Surgical procedures which require transfusions include the trans-plantation of organs, such as the liver and heart, where significant bleeding may occur. Blood may also be given to treat certain diseases, such as anemia. Plasma may also be transfused to treat badly burned patients who have lost significant amounts of fluid or in the treatment of bleeding disorders. Plasma products, such as Factor VIII, t...

  THE DISCOVERY OF THE BLOOD GROUP SYSTEMS It has been known since the seventeenth century that the transfusion of blood between individuals could have rapid and fatal consequences. Fortunately, in 1900 Landsteiner (1868–1943) discovered that individuals could be classified into different groups depending on the characteristics of their erythrocytes and the presence of specific antibodies in their plasma to erythrocyte anti-gens. These discoveries laid the foundations for the routine and safe therapeu-tic transfusion of blood. Landsteiner drew blood from a number of individuals and separated the erythrocytes from the plasma. He then mixed together all possible combinations of erythrocytes and plasma from these individuals together and showed that only certain combinations resulted in the clump-ing or  agglutination  of the erythrocytes ( Figure 6.2 ). These patterns of agglu-tination showed that there were different blood groups, which Landsteiner named A, B and O. In 190...

  THE ABO BLOOD GROUP SYSTEM (ISBT 001) The ABO blood group system classifies people into one of four major blood groups: A, B, AB and O, according to the different type of antigen present on the surfaces of their erythrocytes. The frequencies of these blood groups vary between different populations ( Table 6.3 ). THE ANTIGENS OF THE ABO SYSTEM The antigens that determine ABO blood groups are oligosaccharide constit-uents of cell surface glycolipids and glycoprotein. These sugars are added to an existing chain of oligosaccharides which protrudes from the erythrocyte membrane ( Figure 6.7 ). The  H  gene, located on chromosome 19, encodes an enzyme,  L -fucosyl transferase, which adds  L -fucose to the terminal galactose, to form the H antigen. In blood group O individuals, the H antigen is found on their erythrocytes and also on a variety of other cells. People of blood group A and AB possess the  A  gene, encoded on chromosome 9. This gene encodes...

  THE Rh BLOOD GROUP SYSTEM (ISBT 004) The Rh blood group system divides people into Rh positive and Rh negative groups depending on whether or not their erythrocytes carry the Rh anti-gen. Landsteiner and Wiener discovered this system in 1940. They showed that antisera raised in guinea pigs against erythrocytes from rhesus monkeys reacted with 85% of Caucasian blood donors in New York. The Rh system of blood group antigens is often described as if it is a single antigen. However, it consists of a complex series of antigens, which are specified by two genes:  RHD  and  RHCE . The former encodes the RhD protein which expresses the Dantigen while the latter encodes the RhCcEe protein which carries either the C or c antigen together with the E or e antigen. At one time it was thought that another antigen, termed the ‘d’ antigen, was present when the D antigen was absent. It is now recognized that the d antigen does not exist. However the term is still used to indicate t...

  HEMOLYTIC DISEASE OF THE NEWBORN   Hemolytic disease of the newborn (HDN) is a serious disease characterized by anemia, splenomegaly, hepatomegaly and edema. The condition is caused by the transfer of maternal anti-erythrocyte antibodies across the placenta. The condition may arise in the offspring of women who are RhD negative. Such women may become sensitized to RhD antigen when they give birth to an RhD positive child. At birth, some of the baby’s blood can enter the maternal circulation and the mother will respond by making anti-D antibod-ies. This does not have any clinical consequence for the child itself, but may cause problems during a subsequent pregnancy, if that fetus is RhD posi-tive. Antibodies to Rh antigens are clinically significant during pregnancy because they are of the IgG class. Thus they can cross the placenta and bind to the fetal erythrocytes. Although Rh antibodies are IgG, they do not appear to activate complement. Instead, the antibody-coated eryth...

  OTHER BLOOD GROUP SYSTEMS The Lewis blood group system (ISBT 007, symbol Le) is related the Lewis antigens Le a  and Le b  present on erythrocytes. However, these antigens are not integral parts of the membrane but are soluble plasma proteins which become reversibly adsorbed onto erythrocyte membranes. The levels of bound antigens therefore vary, although the erythrocytes of children 2 years old and above have approximately adult levels. The Le a  and Le b  antigens are not the products of different forms of a single gene, but arise from different actions of a fucosyl transferase that attaches fucose residues to an oligosaccharide known as type-1 precursor oligosac-charide. If the fucose is added to a subterminal position it produces the Le a  antigen, whereas attachment to the terminal position gives the Le b  antigen. Approximately 72% of white populations are Le(a–b+), that is, they lack the Le a  but have the Le b , 22% are Le(a+b–), and 6% ...

  LABORATORY DETERMINATION OF BLOOD GROUPS Traditional methods for determining blood groups rely on the agglutina-tion of erythrocytes by antibodies, usually referred to as hemagglutination. Hemagglutination can be carried out on glass microscopy slides or in micro-titer plates in which agglutination patterns are easily distinguished from the settling of erythrocytes. Recent years have seen increasing use of the Diamed typing system to detect hemagglutination. This is a system which uses mono-clonal typing antibodies, distributed in a gel, contained in individual tubes set in plastic ‘cards’. Cells are added to the antibodies and the cards are cen-trifuged. Where agglutination has occurred, the agglutinates remain on top of the gel, whereas nonagglutinated cells settle through the gel to the bottom ( Figure 6.10 ). Most transfusion laboratories now use gel technology for blood grouping and compatibility testing. Whichever technique is used, a blood group, such as the ABO grouping, ...

  ROLE OF COMPLEMENT IN TRANSFUSION REACTIONS The activation of complement is also involved in some forms of immunological hypersensitivity and can cause some of the prob-lems associated with autoimmune disease . However, given that it amplifies the actions of antibodies, complement can cause many of the problems associated with transfusion reactions. Thus, complement causes lysis of sensitized erythrocytes, that is, erythrocytes coated with anti-erythrocyte antibodies. The classical pathway for complement activation is initiated when IgG or IgM binds to an epitope, in this case on the erythrocyte’s membrane. The antibody could be IgM, as is usually the case with Anti-A or Anti-B, or IgG, as is the case with antibodies to Rh antigens. The binding of antibody to the epitope induces a conformational change in the Fc region of IgG or IgM, allowing the binding of C1 protein. The C1 is comprised of three loosely associated pro-teins called C1q, C1r and C1s. The C1q is a large protein an...

  HAZARDS OF TRANSFUSION One hazard of transfusion is a hemolytic transfusion reaction (HTR) if preex-isting antibodies are present in the recipient. This may result in acute intra-vascular hemolysis, as in ABO incompatibility, or in delayed extravascular hemolysis, as with several of the other blood group systems. Acute intravas-cular hemolysis has serious clinical consequences and, indeed, may be fatal. With delayed extravascular hemolysis the patient may suffer fever and general malaise as the donated erythrocytes are destroyed and the hemoglobin levels fall. To prevent either occurrence, the recipient should be screened before the transfusion for the presence of anti-erythrocyte antibodies. The transfusion of leukocytes may also lead to adverse reactions, such as  nonhemolytic febrile transfusion reactions . Such patients exhibit flushing,fever, rigors and hypotension. These may be caused by the reaction between antibodies and leukocyte antigens in the recipient, resulting...

  SCREENING OF BLOOD DONORS Transfusion scientists must be assured that the process of transfusing blood poses minimal risk to the patient and donor alike. Aside from the obvious need for blood to be carefully matched to avoid a possibly fatal transfusion reaction, it is essential that donors are carefully screened to avoid those who are ill or who may be harmed by giving blood, or whose blood poses a health risk because, for example, it is contaminated with certain viruses even though the donor shows no signs of ill health. In  the UK, blood is taken from healthy donors aged between 17 and 70 and is a voluntary and unpaid activity. Potential donors who are excluded from donation include individuals with HIV or hepatitis viral infections, as well as individuals who are at risk of becoming HIV and/or hepatitis virus positive, for example prostitutes, drug abusers who inject themselves with drugs, and individuals who have had sex with men or women living in Africa ( Table 6.10 )...