It is the responsibility of transfusion medics to ensure that transfused blood is as safe as possible. Due examinations and tests must be carried out on donors and donated blood, respectively. Besides the risk of transfusion transmitted infections (TTI), there is also the possibility of transfusion-associated hemolysis, the risk of which must be reduced as far as possible before a component of blood is issued by the blood bank. Thus, certain pre-transfusion tests have to be carried out to ensure that the transfused blood components have adequate survival when transfused and do not cause harm to the recipient.
The concept of safe transfusion from a red cell serology point of view, which we are familiar with today, was heralded by the discovery of the ABO blood groups by Karl Landsteiner in 1901.[1
] Since then a large number of red cell antigens have been discovered, for example, the Rh antigen in 1940[2
] and the Kell antigen in 1946.
Blood groups are antigens and, by definition, a molecule cannot be an antigen unless it is recognised by an antibody. Thus, all blood group specificities are defined by antibodies. Most adults have antibodies to A or B antigens, or to both; that is, they have ‘naturally occurring’ antibodies to those ABO antigens that they lack. For most other blood groups, the corresponding antibodies are not ‘naturally occurring.’ As of now, according to the International Society of Blood Transfusion (ISBT), there are about 300 blood group antigens.[3
Blood group antibodies are usually IgM or IgG, although some may be IgA. ‘Naturally occurring’ antibodies are usually predominantly IgM, whereas ‘immune’ antibodies are predominantly IgG. However, not all antigens lead to the formation of clinically significant antibodies. Only about 25–28 antigens out of the known 300 are known to cause hemolytic transfusion reactions (HTR). At their worst, HTRs give rise to disseminated intravascular coagulation, renal failure, and death. At their mildest, they reduce the efficacy of the transfusion. The antibodies which cause HTR are termed as clinically significant. Thus, pre-transfusion tests should be such that all the clinically significant antibodies can be ruled out.
In the majority of the blood banks, the conventional method of pre-transfusion testing involves determining the ABO and Rh types of the donor and the recipient, and performing a major cross-match (testing the recipient's serum/plasma against the donor's red blood cells). The pre-transfusion testing should consist of an AHG (Coombs phase) cross-match. The reason for doing an AHG cross-match is to detect red cell antibodies, most of which are non-agglutinating (incomplete) IgG antibodies, although some antibodies are IgM.
Over the last 3–4 decades, pre-transfusion tests have undergone substantial revision. In the early 1960s, many blood banks carried out minor cross-match in addition to major cross-match. It was only in the mid 1970s that the minor cross-match was abandoned, as antibody screening of donor blood became routine.[4
] The standards of most national bodies stipulate that blood from donors with a history of prior transfusion or pregnancy be tested for red blood cell (RBC) alloantibodies; however, most blood banks test all donor blood for RBC alloantibodies because of the difficulty in determining donors’ past histories.
In the late 1970s and early 1980s, the need for doing the major cross-match was also questioned.[5
] In fact, as early as 1964, Groves-Rasmuessen had proposed it be abandoned. It was suggested that the AHG phase of the cross-match added little extra value for improving patient safety when the antibody screen was negative. The basis of this argument was that if the serum or plasma of the recipient is tested in the AHG phase with red cells of two to three un-pooled O group RBCS, the clinically significant RBC alloantibodies can be either detected or ruled out. It is important that the reagent red cells are selected in such a manner that they express the antigens associated with most clinically relevant antibodies. Reagent cells licensed by the Food and Drug Administration (FDA) in the US for this purpose are required to express the following antigens: D, C, E, c, e, M, N, S, s, P1, Lea
, K, k, Fya
, and Jkb
] There are no requirements for other antigens, such as Lua
, V, or Cw. Some weakly reactive antibodies react only with screening red cells from donors who are homozygous for the genes controlling expression of these antigens, a serologic phenomenon called dosage. Antibodies in the Rh, Duffy, and Kidd systems are the ones that most commonly manifest the dosage phenomenon. If the AHG cross-match is carried out between a recipient and a donor, and the donor RBC carries Rh, Duffy, or Kidd antigens in a heterozygous dose, the AHG cross-match may be compatible but, despite this, there will be a hemolytic transfusion reaction. Thus, by providing the important RBC antigens in a homozygous dose, antibody screening cells increase the probability of detection of clinically significant antibodies.
If the antibody screen is negative and the patient has no past history of unexpected antibodies, the presence of an IgG antibody is highly unlikely. It can be predicted that all the ABO-compatible RBC units would then be compatible in an AHG cross-match. ABO and Rh compatible blood can be selected from the stock and issued in less than 10 minutes without carrying out an AHG cross-match (only immediate-spin cross-match is carried out). This is the type and screen method of issuing blood.
On the other hand, if the antibody screen is positive, as will be the case in approximately 1% of patients, the antibody can be identified using a cell panel and antigen negative blood be provided. This would usually take a couple of hours, unless there are multiple antibodies or antibodies against high-frequency antigens.
Performing antibody screening tests before or instead of a cross-match permits early recognition and identification of clinically significant antibodies and makes the decision about immediate-spin cross-match easier. When the recipient has no clinically significant red cell antibodies and no history of such antibodies, it is extremely rare for the AHG cross-match to be incompatible or to detect a clinically significant unexpected antibody. At the same time, pre-cross-match detection of antibodies allows more time to screen for donor units that lack the relevant antigen, facilitating the timely provision of blood for transfusion. The transfusion service may even adopt the computer cross-match eventually.[7
] The type and screen method is extremely useful where the chance that the patient will be transfused is low. If the status of the patient changes and transfusion is required, blood can be released by the blood bank within 10–15 minutes. For patients who currently have, or have previously had, a clinically significant antibody, the cross-match method must include AHG testing as well ABO incompatibility testing.
Even though well accepted and practiced in many countries, there has been criticism of the type and screen policy in some countries because of the following reasons:
- Antibodies might be missed if the screening cells have only a single dose or weak expression of the corresponding antigen.
- Antibodies might be missed if the corresponding antigens are not present on the screening cells.
- Some antigens could be present in Asian/Indian populations, while being absent in Caucasians who may be the source of the reagent red cells used for antibody screening. A good example of this would be the Mi(a) antigen.
The type and screen policy was well studied in North America and other countries before being implemented. One study in the US involved a series of more than 32000 recipients,[5
] whereas another study in Canada studied close to 10000 recipients.[9
We carried out this study to test the hypothesis that the type and screen procedure is a safe method for pre-transfusion testing when compared to the AHG cross-match that is currently in use in India. We also wanted to study if the commercially available screening cell panels manufactured using red cells from Caucasian donors are safe for use in India. Another objective was to study the distribution of the different types of alloantibodies in Indian population.