Pathology
Immune Responses
Regarding blood groups, which of the following statements is CORRECT:
Answer:
The protein that defines the ABO antigens is encoded from a single gene for which there are three major alleles, A, B and O. The A and B alleles catalyse addition of different carbohydrate residues to a basic antigenic glycoprotein or glycolipid with a terminal l-fructose on the red cell, known as the H substance. The O allele is non-functional and thus does not modify the H substance.Blood Groups
Pathology / Immune Responses
Last Updated: 4th July 2021
Approximately 400 red blood cell group antigens have been described. Human red blood cells carry many antigens on their surfaces. The most important of these antigens belong to the ABO system and the rhesus (Rh) system. The D antigen is the most important antigen of the rhesus system.
Immune Response
The ABO group antigens are unusual in that naturally occurring antibodies occur in the plasma of subjects who lack the corresponding antigen, even if they have not been exposed to that antigen previously. The most important of these natural antibodies are anti-A and anti-B, which are usually IgM.
Immune antibodies develop in response to the exposure by transfusion or by transplacental passage in pregnancy to red cells possessing antigens that the subject lacks. These antibodies are commonly IgG, although some IgM may also develop in the early phase of an immune response. Only IgG antibodies are capable of transplacental passage and the most important immune antibody is the Rh antibody, anti-D.
ABO
The protein that defines the ABO antigens is encoded from a single gene for which there are three major alleles, A, B and O. The A and B alleles catalyse addition of different carbohydrate residues to a basic antigenic glycoprotein or glycolipid with a terminal l-fructose on the red cell, known as the H substance. The O allele is non-functional and thus does not modify the H substance.
The ABO blood group phenotypes are O (genotype OO), A (genotype AA or AO), B (genotype BB or BO) and AB (genotype AB).
Blood group O is the most common in the UK (46 %), followed by group A (42 %), group B (9 %) and finally group AB (3 %).
- Blood group O has no antigens, but both anti-A and anti-B antibodies and thus is the universal donor.
- Blood group AB has both A and B antigens but no antibodies and thus is the universal recipient.
- Blood group A has A antigens and anti-B antibodies and blood group B has B antigens and anti-A antibodies.
![By OpenStax College [CC BY 3.0 (https://creativecommons.org/licenses/by/3.0)], via Wikimedia Commons](https://primary-cdn.frcemsuccess.com/wp-content/uploads/2018/09/781px-1913_ABO_Blood_Groups.jpg)
Blood Groups. (Image by OpenStax College [CC BY 3.0 (https://creativecommons.org/licenses/by/3.0)], via Wikimedia Commons)
Rh D
The RhD gene may be either absent or present, giving the RhD negative or RhD positive phenotype respectively. About 85% of the UK population is Rh D positive. Anti-D antibodies don't occur naturally, and are therefore immune antibodies that result from previous transfusions or pregnancy. The indirect Coombs test is used for routine antibody screening e.g. in pregnancy or prior to a blood transfusion.
Rhesus Disease
A baby inherits its blood type from both parents. Therefore a mother who is RhD negative can carry a baby who is RhD positive. During pregnancy small amounts of fetal blood can enter the maternal circulation. The presence of fetal RhD-positive cells in her circulation can cause a mother who is RhD negative to mount an immune response, producing a template for the production of antibodies as well as small amounts of antibodies against the RhD antigen (anti-D antibodies). This process is called sensitisation or alloimmunisation.
Sensitisation can happen at any time during pregnancy, but is most common in the third trimester and during childbirth. Sensitisation can follow events in pregnancy, such as medical interventions (chorionic villus sampling, amniocentesis or external cephalic version), terminations, late miscarriages, antepartum haemorrhage and abdominal trauma. It can also occur in the absence of an observed potentially sensitising event. Once sensitisation has occurred it is irreversible.
The process of sensitisation has no adverse health effects for the mother and usually does not affect the pregnancy during which it occurs. However, if the mother is exposed to the RhD antigen during a subsequent pregnancy, the immune response is quicker and much greater. The anti-D antibodies produced by the mother can cross the placenta and bind to RhD antigen on the surface of fetal red blood cells. These antibody-coated fetal red blood cells are removed from the fetal circulation. Fetal anaemia results if the red blood cells are removed faster than they are produced. Severe anaemia can lead to fetal heart failure, fluid retention and swelling (hydrops), and intrauterine death.
When red blood cells are broken down, bilirubin is released. In utero this is cleared by the placenta and is not harmful. However, after birth the neonatal liver cannot cope with the excess production of bilirubin, and this leads to jaundice (haemolytic disease of the newborn or HDN). Before birth, anaemia and hydrops can be managed with intrauterine transfusions, but this carries a 2% risk of fetal loss. When red blood cells are broken down, bilirubin is released. In utero this is cleared by the placenta and is not harmful. However, after birth the neonatal liver cannot cope with the excess production of bilirubin, and this leads to jaundice (haemolytic disease of the newborn or HDN). Low levels of jaundice are not harmful but, if left untreated, higher levels can result in damage to specific areas of the neonatal brain, causing permanent brain damage (kernicterus). This can lead to a range of neurodevelopmental problems, such as cerebral palsy, deafness, and motor and speech delay. Postnatal jaundice can be treated with phototherapy and exchange transfusion.
The risk of sensitisation can be reduced by administering anti-D immunoglobulin to women in situations in which feto-maternal haemorrhage is likely (after delivery, miscarriage, abortion, invasive procedures or abdominal trauma). Potentially sensitising events introduce a quantity of fetal RhD antigen into the maternal circulation. The anti-D immunoglobulin administered neutralises this fetal antigen. In addition, anti-D immunoglobulin can be administered routinely in the third trimester as prophylaxis against small amounts of feto-maternal haemorrhage that can occur in the absence of observable sensitising events. This is known as routine antenatal anti-D prophylaxis (RAADP).
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
