From approximately 1960 to 1984, the purpose of the major crossmatch was to detect unexpected antibodies in the serum of the recipient, and it also acted as a check on a previous antibody screen. It also served as a check on ABO typing, since a mistake in ABO typing may result in RBCs from the donor being incompatible with naturally occurring ABO antibodies in the serum of the recipient.

The most widely used crossmatch technique from approximately 1960 to 1984 consisted of three sequential parts. First, donor RBC and saline-diluted recipient serum were incubated at 25°C to detect bivalent antibodies. Next was incubation at 37°C with 22% albumin (or other albumin concentration), added to enhance agglutination of univalent antibodies such as the Rh group. Finally, a Coombs’ test that detected weaker univalent antibodies was performed. Many laboratories are substituting low ionic strength saline (LISS) reagent for albumin, which decreases incubation time from 30 minutes to 15 minutes. It has the same or slightly better sensitivity as the albumin reagent, with a minor disadvantage that LISS detects more antibodies that turn out to be clinicallyunimportant than does albumin.

Unfortunately, the major crossmatch will not detect the most common ABO incompatibility error, which is patient identification mistakes, either crossmatch specimens obtained from the wrong patient or properly crossmatched blood transfused into the wrong patient. Also, the procedure will not detect errors in Rh typing if no Rh antibodies are present in donor or recipient blood. Since Rh antibodies do not occur naturally, either donor or recipient would have to be previously sensitized before Rh or similar antibodies would appear. Since the crossmatch is designed to detect antibodies, not antigens, the crossmatch does not demonstrate antigens and thus will not prevent immunization (sensitization) of the recipient by Rh or other non-ABO blood groups. This can be done only by proper typing of the donor and recipient cells beforehand.

The AABB, in their 1984 Blood Bank Standards, made a major departure from the “traditional” crossmatch by relying on precrossmatch ABO and Rh typing and the antibody screen of the recipient serum plus only the “immediate spin” saline part of the major crossmatch procedure to check for technical errors in typing. The immediate spin method entails centrifugation and examination of donor blood RBC and recipient serum in saline diluent without incubation, which takes only about 5 minutes. To substitute the immediate spin crossmatch for the traditional major crossmatch it is necessary to do a pretransfusion recipient antibody screen without finding any unexpected antibodies (if the screen did detect antibodies, the traditional crossmatch would have to be done). This protocol removes considerable pressure from the blood bank since ABO typing and recipient serum antibody screen are usually performed well in advance of the actual order to transfuse. It also saves a significant amount of time and money. Studies indicate that about 0.06% (range, 0.01%-0.4%) of recipient units will contain antibody that will be missed (although the majority of these would not be likely to produce life-threatening hemolysis). Other studies found that crossmatch alone detected about 4% (range, 1%-11%) of total antibodies detected by combined antibody screen and crossmatch. There was considerable debate about how far to go in altering the traditional crossmatch procedure and whether or not to perform it in all cases. Nevertheless, the new policy has been in effect for nearly 10 years without major problems, so there is now much less controversy.

Occasionally the laboratory is asked to do an emergency crossmatch. Those institutions using the current AABB protocol already have a single 5-minute procedure that it would not be possible to shorten. Those institutions using the traditional crossmatch should reach an agreement with the medical staff as to what would be done if an emergency crossmatch is requested. One or more steps in the crossmatch procedure can be eliminated to gain speed, but each omission produces a small but definite risk of missing an unexpected serious problem. There also should be agreement about what would be done in emergency conditions if the patient has antibodies against blood groups other than ABO and Rh or has an unidentified antibody.

Gamma globulin concentrate for intravenous therapy (IV-GG) often contains one or more antibodies (about 50% of IV-GG lots tested in one study). In one report, about 65% of the antibodies detected were anti-D. Patients receiving IV gamma globulin therapy may receive detectable amounts of the antibody or antibodies in the gamma globulin, which might cause problems if the blood bank is not informed that IV-GG is or was being given.