Chapter 73 – Transfusion




Abstract




As discussed in Chapter 8, red blood cells (RBCs) can be thought of as ‘bags of haemoglobin’ (Hb). However, the composition of the ‘bag’ itself differs between patients. The RBCs have surface antigens that act as markers, identifying the RBC to the immune system. RBC surface antigens may be polypeptides, polysaccharides or glycoproteins. Which specific antigens are expressed is determined genetically.





Chapter 73 Transfusion




What are red blood cell antigens?


As discussed in Chapter 8, red blood cells (RBCs) can be thought of as ‘bags of haemoglobin’ (Hb). However, the composition of the ‘bag’ itself differs between patients. The RBCs have surface antigens that act as markers, identifying the RBC to the immune system. RBC surface antigens may be polypeptides, polysaccharides or glycoproteins. Which specific antigens are expressed is determined genetically. There are at least 30 different RBC antigen systems, the most important of which are:




  • The ABO blood group system;



  • The Rhesus (Rh) blood group system.


Minor blood group systems include Kell, MNS, Lewis, P and Duffy.



Describe the ABO system


As well as being the first RBC antigen system discovered, the ABO blood system remains the most important for blood transfusion. The ABO blood groups are carbohydrate-based antigens. All patients’ RBCs have a disaccharide ‘core’ antigen, called the H antigen. Patients then fall into one of four blood groups:




  • Group O. These patients’ RBCs only express the H antigen; ‘O’ signifies that no other sugars are added.



  • Group A. An additional carbohydrate group (N-acetylgalactosamine) is bound to the H antigen, making a trisaccharide: the A antigen.



  • Group B. A different carbohydrate group (d-galactose) is bound to the H antigen, making a different trisaccharide: the B antigen.



  • Group AB. These patients’ RBCs express both A and B antigens.


In the UK, the most common blood groups are O (44%) and A (42%). Group B makes up 10%, while group AB is found in only 4% of patients.



What is the Rh system?


The Rh blood group is the second most important in transfusion medicine. It is named after the Rhesus monkey, the animal whose blood was used in the discovery of the Rh system. There are 50 different Rh antigens discovered to date, of which the most important are: D, C, c, E and e. By far the most important Rh antigen is D – this is the antigen that is present when patients are referred to as being Rhesus positive, Rh factor positive or RhD positive.


The RhD antigen is a large (30‑kDa) cell membrane protein that is thought to be a subunit of an ammonia transport protein. As with other blood group systems, the presence or absence of the RhD antigen on a patient’s RBCs is genetically determined – around 85% of the UK population are RhD positive.



Why does the immune system develop antibodies to RBC antigens?


The immune system develops antibodies to fragments of foreign material presented by antigen-presenting cells (see Chapter 75). Patients may develop antibodies to non-self RBC antigens for two reasons:




  • Exposure to foreign RBCs, such as following a blood transfusion or placental abruption.



  • Exposure to environmental antigens (food, bacteria, etc.) that happen to have a chemical structure similar to that of a non-self RBC antigen results in the production of antibodies that also cross-react with non-self RBCs.


The two main blood groups exemplify this:




  • ABO blood group system. At birth, antibodies to non-self ABO antigens are not present: they appear in the plasma from around 6 months of age. Antibody development is thought to be an immune response to environmental antigens that have a similar chemical structure to the ABO antigens. As a result, antibodies are raised to non-self antigens:




    1. Blood group O: develop anti-A and anti-B antibodies;



    2. Blood group A: develop anti-B antibodies only;



    3. Blood group B: develop anti-A antibodies only;



    4. Blood group AB: do not develop anti-A or anti-B antibodies.

    The anti-A and anti-B antibodies produced are immunoglobulin M (IgM). This is important as IgM is unable to cross the placenta – if it could, every foetus of a different ABO blood group to the mother would have its RBCs attacked by the maternal immune system.



  • Rh blood group system. In contrast to the ABO blood group system, the 15% of the population who are genetically RhD antigen negative do not naturally develop RhD antibodies. Anti-RhD antibodies are only acquired on exposure to foreign RBCs carrying the RhD antigen. Clinically, this may occur due to:




    1. Incompatible blood transfusion. Transfusion of RhD-positive blood into an RhD-negative patient will trigger anti-RhD antibody production.



    2. Foetal–maternal haemorrhage. If the blood of an RhD-positive foetus and RhD-negative mother mix (e.g. following childbirth, abortion, trauma or placental abruption), the maternal immune system will be exposed to RhD antigen and will develop anti-RhD antibodies.

    Unfortunately, RhD antibodies are usually IgG and are therefore able to cross the placenta.




Clinical relevance: Rh disease


Rh disease affects RhD-negative mothers with RhD-positive offspring. When an RhD-negative mother is exposed to RhD-positive foetal blood (e.g. following trauma), her immune system produces anti-RhD IgG. Maternal anti-RhD IgG is then able to cross the placenta and attack the RBCs of an RhD-positive foetus, either for the same or a subsequent pregnancy. The foetus develops a severe anaemia in utero and, if the foetus survives to birth, Rh disease (haemolytic disease of the newborn).


RhD-negative mothers are given anti-RhD immunoglobulin once or twice during pregnancy and at delivery in an attempt to prevent maternal sensitisation to RhD. The parenteral anti-RhD IgG binds any foetal RBCs that pass into the maternal circulation.



What is meant by the terms ‘allogenic’ and ‘autologous’ blood transfusion?


Allogenic blood transfusion is where donor blood – usually packed RBCs – is given intravenously to a recipient. In contrast, autologous blood transfusion is where blood is taken from a patient and reinfused back into the same patient when required (e.g. intraoperative cell salvage, preoperative autologous blood donation, acute normovolaemic haemodilution).



What is meant by the term ‘haemolytic transfusion reaction’?


Early allogenic blood transfusions were fraught with complications: many patients died after receiving incompatible blood. It was not until the ABO blood group system was discovered that the reasons for these deaths became clear.


A haemolytic transfusion reaction will occur if the recipient’s plasma contains antibodies that are reactive against the donor’s RBC antigens. The recipient’s antibodies coat the donor RBCs: the antibody–antigen complex activates complement, leading to haemolysis of donor RBCs. Haemolytic transfusion reactions are of two types:




  • Immediate haemolytic transfusion reaction. ABO incompatibility causes rapid intravascular haemolysis, with the severity depending on the antibody titre. Urticaria, flushing, chest pain, dyspnoea, jaundice, tachycardia, shock, haemoglobinuria and disseminated intravascular coagulation may occur. Transfusion of RhD-incompatible blood tends to result in extravascular haemolysis, which is usually less severe than intravascular haemolysis.



  • Delayed haemolytic transfusion reaction. Minor RhD antigens and the minor blood group systems may cause a delayed haemolytic transfusion reaction, occurring 7–21 days following transfusion. Delayed transfusion reactions are difficult to prevent. Following a prior exposure to a blood antigen, patients develop a low titre of antibody – too low for laboratory detection. When incompatible blood is transfused, a secondary immune response occurs: it takes time for new IgG antibodies to be produced, leading to a delay before haemolysis is evident.

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Sep 27, 2020 | Posted by in ANESTHESIA | Comments Off on Chapter 73 – Transfusion
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