NOTES ON BLOOD TRANSFUSION

A Blood Care Foundation Guide

Introduction

If blood of the wrong group is transfused to a patient, a transfusion reaction can occur. This is due to antigens (Ags) on the transfused cells reacting with antibodies (Abs) in the patient's plasma. Reactions, as described in para 9 below, can vary from mild to fatal, but the most important ones are due to Ags on the red blood cells (RBCs).

RBC Blood Groups
The ABO System

The ABO system was first described by Landsteiner in 1900. There are 3 Ags in this system A, B and H. These Ags, which are determined by terminal sugars attached to various proteins and glycolipids in the RBC membrane, are the most common Ags on the RBC surface. The A and B Ags are co-dominant and H is recessive. During the first 6 months of life, the body will produce so-called "naturally occurring antibodies" to those Ags, which are lacking on the RBC membrane. These Abs are thought to be produced as a result of stimulation by Ags, found on the surface of normal bowel bacteria, which are virtually identical to the ABO Ags. These ABO Abs are a mixture of IgM and IgG, are complement fixing and have a very wide thermal range of reaction, being active from 4⁰ to 37⁰C. They are capable of causing intravascular haemolysis if blood of the wrong group is transfused.

When Landsteiner described the ABO system, he initially described 3 groups. Those that carried the A Ag, which he designated Group A, those that carried the B Ag, which he designated Group B and those that carried no Ags, which he designated Group Nought (0). The last group, Group 0, later came to be corrupted to Group O. The next year he described a fourth group where, as the A and B Ags are co-dominant, a person inheriting the A Ag from one parent and the B Ag from the other will be group AB. The H Ag is recessive and is carried by everyone, with the exception of less than 100 people in the world, who are of the Bombay Group and who will not be discussed further. People who only carry the H Ag are Group O, but those who are heterozygous, AH or BH, will be Group A or B respectively. There is no difference in the strength of reaction shown by heterozygous, AH or BH, and homozygous, AA or BB, people. The ABO genes are found on chromosome 9.

The Rhesus (Rh) system is slightly more complicated because it is composed of 3 closely linked allelic genes on chromosome 1, each with 2 alleles, namely C and c, D and d, and E and e. A person inherits one set of alleles of the 3 Rh genes, known as a haplotype, from each parent, for example CDe from one parent and cde from the other. C, D and E are dominant alleles and c, d and e are recessive. Table 1 lists the common haplotypes with their frequency.

The D Ag is highly immunogenic, being at least 20 times more immunogenic than any of the other Rh Ags, and so its presence or absence determines whether a person is Rh Positive or Rh Negative. The normal notation for this is Rh (D) Pos or Rh (D) Neg. The + and - signs are never used to indicate Pos and Neg as these can so easily be altered, especially - to +. Abs can be raised to all the alleles except d, which is presumed to be amorphic. There are virtually no naturally occurring Abs to the Rh Ags, but the transfusion of Rh (D) Pos blood to a Rh (D) Neg recipient usually causes the formation of anti-D IgG Abs, which can cause a haemolytic reaction should a further transfusion of Rh (D) Pos blood be given. More importantly anti-D Abs are a potent causation of haemolytic disease of the newborn (HDN).

Table 1. Frequency of common Rh haplotypes

* Symbols based on the work of Wiener and Race. R implies that the gene determines D and r that it does not.
# These frequencies, for an English population, are derived from Race.

Normal procedure

When considering the ABO group, blood for transfusion should, whenever possible, be group identical. In cases where this is not possiblegroup compatible blood, that is blood, the RBCs of which, do not carry Ags against which the recipient has Abs. Table 2 shows which alternative ABO groups are compatible with the ABO group of the patient.

Table 2. ABO compatible groups

Blood for transfusion should be of the same Rh D group as the patient, that is to say patients with the D Ag should receive Rh (D) Pos blood and those with the d Ag should receive Rh (D) Neg blood. In cases of extreme emergency, when no Rh (D) Neg blood is available, it is permissible to give Rh (D) Pos blood to males and females over the age of 50 years, if they have never received Rh (D) Pos blood before and, in the case of females, they have not developed anti-D Abs during a pregnancy. On no account should Rh (D) Pos blood be given to females under the age of 50 years because of the danger of raising Abs which could lead to HDN in a future pregnancy.

There are 19 other major blood group systems, but their importance lies only in their ability to produce transfusion reactions (HTRs) and/or HDN. Table 3 lists the most common Abs and divides them by their ability to cause a haemolytic transfusion reaction and/or HDN.

Table 3 - Clinical significance of other blood group systems

Problems
Transfusion Reactions

These, which are listed in Table 4, are probably the most frequent adverse reactions to blood transfusion. An acute intravascular HTR, which is frequently fatal, is the most important, but fortunately the most infrequent. Such reactions most commonly occur due to the transfusion of blood incompatible by the ABO system. The reaction usually occurs within the first 5 to 10 minutes of a transfusion. The incompatible RBCs lead to activation of the complement and coagulation systems. This in turn cause shock, DIC and renal damage and is manifested by dyspnoea, chest pain, fever, oliguria, hypotension and later haemoglobinuria.

Delayed HTRs are not usually fatal and often are only discovered when the patient's haemoglobin level and haematocrit fail to demonstrate the expected post-transfusion rise. However the patient will have been primed and will have formed Abs to the specific Ag and a further transfusion of blood, incompatible to that Ag could lead to an acute intravascular HTR.

Table 4 - Immunological and Allergic Reactions

White cell reactions, with the exception of graft-v-host disease and TRALI, are usually of little clinical significance and are manifested by a mild pyrexia and an urticarial reaction. These, as well as the platelet and miscellaneous reactions, can usually be controlled by the administration of an anti-pyretic and/or an anti-histamine.

Haemolytic disease of the New-born

HDN was a common cause of peri-natal death before the introduction of the routine administration of anti-D Ig to Rh (D) Neg mothers who had delivered a Rh (D) Pos child. Other Rh Abs are now more of a problem with anti-c and anti-E being the most prominent. If blood is required for an exchange transfusion, fresh whole blood, less than 5 days old, should be supplied. RBCs in SAG-M, or any other optimal additive solution, are not suitable for exchange transfusions. In all of these cases, it is advisable to discuss the matter with the BCF Clinical Director.

Patient with preformed antibodies

The first point to evaluate is the significance of the Ab. Table 3 lists the most common Abs and divides them by their clinical significance. Those that do not bind complement or are only active at a thermal range below 30⁰C are of little or no clinical significance and can usually be ignored. In cases where the Ab is active at 37⁰C and can cause an acute haemolytic reaction, the BCF Authorised Blood Bank should be contacted and blood, which lacks the Ag against which the Ab is directed, should be requested. If no such blood is available the case should be discussed with the BCF Clinical Director before any further action is taken.

Numerical notation for the ABO system

Soon after Landsteiner described the ABO system, 2 other workers described the same system, but gave the groups a numerical notation. Moss¹, in the USA, described Group O as Group IV and AB as Group I, whereas Jansky², in Europe, described Group O as Group I and AB as Group IV. Both systems described Group A as Group II and Group B as Group III. Some hospitals in Eastern Europe still use the numerical notation. Before ordering blood it is vital to establish which notation the doctor is using. Asking for the blood group distribution within that country best does this. Whichever numerical group is the commonest, this group will be Group O, then A followed by Group B with Group AB being the least common. These 2 notations should not be confused with the new 6-figure notation, which is being developed by the International Committee for Standardisation in Haematology.

References

1. Moss WL. Studies on isoagglutinins and isohaemolysins. Bulletin John's Hopkins Hospital. 1910;21:63-70.
2. Jansky J. Haematologicke studie u. psychotiku. Sb. Klin. Praza 1907;8:85-139

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