INTRODUCTION — An essential goal in transfusion medicine is that red blood cell (RBC) units selected for transfusion be compatible with the patient. The clinical and serologic evaluation, which allows for the transfusion of the appropriate unit(s), requires a joint effort between the clinician and the transfusion medicine physician [1].
However, there are times when all available resources are exhausted and a unit of blood that is not crossmatch compatible must be issued to the patient. The most common of these clinical situations as well as suggestions on how safely to issue and transfuse the best unit of blood available will be reviewed here. General discussions of crossmatching procedures and red cell antigens are presented separately. (See "Pretransfusion testing for red blood cell transfusion" and "Red blood cell antigens and antibodies".)
CROSSMATCHING (COMPATIBILITY) OVERVIEW — When blood is ordered for transfusion, a sample of blood is obtained from the patient, and the transfusion service typically performs type and screen and crossmatching tests on the patient's red blood cells (RBCs) and plasma:
●A type test of the patient's RBCs to determine the ABO and RhD types. (See "Pretransfusion testing for red blood cell transfusion", section on 'Interpretation of pretransfusion testing results'.)
●An antibody screen of the patient's plasma to determine the presence of antibodies directed against RBC antigens. (See "Pretransfusion testing for red blood cell transfusion", section on 'Interpretation of pretransfusion testing results'.)
●A crossmatch also known as a compatibility test uses the patient's plasma and the donor RBCs to determine if the patient's plasma is compatible with the donor's RBCs. (See "Pretransfusion testing for red blood cell transfusion", section on 'Interpretation of pretransfusion testing results'.)
The antibody screen test involves the mixing of the patient's plasma with two or three reagent samples of RBCs on which are represented all of the clinically important RBC antigens. If negative results are obtained, the patient may be safely transfused with ABO and Rh compatible blood, since the patient has no clinically significant RBC antibodies. (See "Pretransfusion testing for red blood cell transfusion", section on 'Interpretation of pretransfusion testing results'.)
On the other hand, if a positive test is found with one or more of the screening cells, an antibody identification test is indicated to evaluate the identity of the antibody. This involves testing the patient's plasma against a panel of 10 or more phenotyped RBCs. This usually results in identification of the RBC antibody in the patient's plasma. Compatible blood may then be selected that lacks the corresponding antigen(s).
At times, the patient's plasma reacts with all of the RBCs on the panel (panagglutination), resulting in incompatible crossmatches with all of the donor blood available, making antibody identification and selection of compatible blood complicated [2]. (See "Pretransfusion testing for red blood cell transfusion", section on 'Interpretation of pretransfusion testing results'.)
There are three major clinical situations that may lead to difficulty in providing crossmatch compatible blood:
●Alloantibodies due to previous transfusions or pregnancy
●Autoantibodies reacting with common RBC antigens in autoimmune hemolytic anemia (AIHA) and some forms of drug-induced immune hemolytic anemia
●Difficulty determining the patient's ABO type (ie, ABO discrepancies)
These situations are each discussed in detail below.
INITIAL EVALUATION AND MANAGEMENT
Communication between clinical team and transfusion team — Laboratory testing to identify complex antibodies and provide compatible blood for transfusion can be very time consuming (algorithm 1). Therefore, communication between the clinician and the transfusion physician is crucial in this setting:
●Laboratory personnel must let the clinician know the complexity of the laboratory testing, the estimated timeframe required to complete the testing, and what kind of patient history would be helpful to find possible causes of the incompatibility.
●The clinician must let the laboratory know the clinical urgency of transfusion, detailed pertinent history, and a treatment plan related to managing anemia and other concurrent medical problems.
The best scenario occurs when the patient with an incompatible crossmatch is not in need of urgent transfusion. This allows for a complete immunohematologic evaluation and provision of compatible blood.
However, for patients who are profoundly anemic and in urgent need of transfusion, a decision must be made based on an abbreviated laboratory evaluation. While this is being accomplished, the clinician can modify patient care (eg, oxygen supplementation, bed rest to decrease oxygen demand) while waiting for the availability of compatible blood [3]. A discussion of procedures that may be employed during this interim period can be found elsewhere. (See "The approach to the patient who declines blood transfusion", section on 'The actively bleeding patient'.)
Patient history — The patient's medical history is very important and may provide clues to the cause of the incompatibility.
●A history of use of certain drugs (eg, methyldopa, procainamide, fludarabine) suggests that the patient may have drug-induced autoimmune hemolytic anemia (AIHA) [4,5].
●A history of a lymphoproliferative disorder (particularly chronic lymphocytic leukemia), autoimmune disease (particularly systemic lupus erythematosus), or immune deficiency disorder (particularly AIDS) suggests secondary AIHA. (See "Warm autoimmune hemolytic anemia (AIHA) in adults".)
●A history of pregnancy or prior transfusion raises the possibility of multiple RBC alloantibodies [6-8]. If there is no history of transfusion in a man or a child, the likelihood that the patient has a significant RBC alloantibody is extremely low, if not impossible. (See "Pretransfusion testing for red blood cell transfusion", section on 'Interpretation of pretransfusion testing results'.)
●A history of difficulties in finding blood for family members suggests the presence of an alloantibody against a high frequency antigen. (See 'Alloantibodies to high frequency antigens' below.)
●A history of recent transfusion raises the possibility of a delayed hemolytic transfusion reaction. (See "Hemolytic transfusion reactions", section on 'Delayed hemolytic transfusion reactions and delayed serologic transfusion reactions'.)
Immediate management — Given the time required to perform the appropriate testing, the severity of the patient's condition determines clinical management during the laboratory evaluation. Thresholds for transfusion are discussed in detail separately. However, the use of thresholds is not appropriate in patients with active bleeding whose blood loss outpaces serial hemoglobin measurements; clinical judgment must be used regarding the urgency of transfusion in such settings. (See "Indications and hemoglobin thresholds for red blood cell transfusion in the adult".)
The patient's ability to withstand severe anemia while awaiting transfusion can be maximized by enforced bed rest to decrease oxygen demand and the administration of supplemental oxygen to optimize dissolved oxygen in the plasma. In critical situations other options may be available. These are described separately. (See "The approach to the patient who declines blood transfusion", section on 'The actively bleeding patient'.)
A detailed history regarding prior transfusions and pregnancies is very important. If the patient has never been exposed to any foreign RBCs in the past, it is highly unlikely that an alloantibody could be present. With this vital information, transfusion can proceed more quickly with ABO matched blood [8,9]. The remainder of the work-up can be completed after issue of the unit of blood.
For patients who require urgent or emergent transfusion, joint decision making by the clinician and transfusion medicine physician should occur [1]. Importantly, no patient should be denied a lifesaving transfusion because of difficulties in finding compatible blood.
For patients with an urgent need for transfusion, blood can be issued under a nonstandard release that is approved by a physician or as an emergency release. Patients with a confirmed ABO type can receive uncrossmatched, type-specific blood, and patients without an available ABO type can receive type O blood. (See "Pretransfusion testing for red blood cell transfusion", section on 'Emergency release blood for life-threatening anemia or bleeding'.)
Massive transfusion is a special case of urgent/emergency transfusion in a patient with a massive hemorrhage, in which predetermined blood ordering protocols are used to provide sufficient numbers of RBC units and other blood components. Many institutions have massive transfusion protocols for specific clinical settings such as labor and delivery. This subject is discussed in detail separately. (See "Massive blood transfusion".)
Emergency transfusion with incompatible blood may be necessary in patients with severe bleeding who have multiple alloantibodies, alloantibodies to high-frequency antigens, autoantibodies, or ABO discrepancy. (See 'Alloantibodies' below and 'Autoantibodies' below and 'ABO discrepancies' below.)
We urge that the best practice for attempting to transfuse these patients safely is to infuse blood slowly while carefully observing the patient for signs and symptoms of an acute hemolytic transfusion reaction (eg, fever, chills, respiratory distress, or pain in the chest or back). In the event of such signs or symptoms, the transfusion should be discontinued immediately.
ALLOANTIBODIES — Alloantibodies against RBC antigens can be produced by patients who have been exposed to foreign RBCs by transfusion or pregnancy. Particular difficulty in providing compatible blood is encountered when such patients form either multiple alloantibodies or an antibody to a high frequency RBC antigen [8-10].
Common alloantibodies — Whenever the antibody screening test is positive, the blood bank will perform studies to identify the specificity of the offending antibody or antibodies (figure 1). The most common alloantibodies detected are anti-E, anti-Le(a), anti-K, anti-D, and anti-Le(b) [11]. Only antibodies that are capable of causing a hemolytic transfusion reaction or hemolytic disease of the fetus and newborn are considered clinically significant. Fortunately not all alloantibodies are clinically important. The following is a list of the common alloantibodies and their clinical significance [12].
●Antibodies that are ALWAYS considered to be potentially clinically significant include: ABO (A, B), Rh (D, C, c, E, e), Duffy (Fya, Fyb), Kidd (Jka, Jkb), Kell (K, k), SsU (S, s, U), and Lutheran (Lub)
●Antibodies that are rarely or never considered to be clinically significant include: Lewis (Lea, Leb), MN, Lutheran (Lua), P1, Xga, Cartwright (Yta), Bg, York (Yka), Chido/Rodgers (Cha/Rga), Sda, and HTLA (high titer low avidity)
In four series, the most frequent clinically significant alloantibodies encountered included anti-E, anti-K, anti-c, anti-Jk(a), and anti-Fy(a) [9,13-15].
Alloantibody persistence and evanescence — Of importance, the titer of some acquired alloantibodies decreases with time, often to the point of evanescence or complete disappearance [16]. This is a less common finding with antibodies directed against Rh antigens, but is frequent among those developing anti-Jk(a), consistent with the large relative number of delayed hemolytic transfusion reactions mediated by anti-Jk(a). As an example, in a long-term study of the transfusion records of 304 male veterans with one or more alloantibodies and at least one follow-up alloantibody screening test, anti-D and anti-C alloantibodies were persistent in 94 and 86 percent, whereas anti-Jk(a) alloantibodies were persistent in only 21 percent [17].
Multiple alloantibodies — After initial alloimmunization, 20 to 25 percent of non-hematology-oncology patients and 22 to 33 percent of hematology-oncology patients may develop additional red cell alloantibodies after subsequent transfusions [13,18]. As examples:
●In one 10-year retrospective study of 564 patients with malignant hematologic disease, of the 51 patients who developed alloantibodies, 34, 14, and 3 produced one, two, and three different alloantibodies, respectively [13].
●In a study of 390 alloimmunized pregnant women who had delivered 455 infants, a combination of two to four different alloantibodies was detected in 27 percent of the women [19]. Combinations of alloantibody specificities appeared to be more harmful to the fetus/infant than single specificities, suggesting a potentially synergistic effect.
●In a review of transfusion records at a Veterans Affairs medical center, multiple alloimmunization occurred in 21.7 percent of alloimmunized patients [20]. The most common alloantibody pairs were anti-K/-E, anti-D/-C, and anti-E/-c.
If massive bleeding occurs in patients with multiple alloantibodies, the hemolytic potential of each specificity should be considered.
Sickle cell disease — A similar situation occurs in patients with sickle cell disease (SCD) who require multiple transfusions during their lifetime. Approximately 25 percent of adults and 10 percent of children with SCD have multiple alloantibodies [21]. This situation arises due to genetic differences among different ethnic populations in terms of the frequency of RBC antigens (table 1) [12].
Patients with SCD are often of African descent, while most blood donors are of European descent, resulting in unusually excessive exposure to certain antigens. The most common antibodies encountered in SCD patients are anti-E (21 percent), -C (14 percent), -K (14 percent), -Fy(a) (7 percent), -Jk(b) (5 percent), -S (4 percent), and –D (4 percent) [21]. (See "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques", section on 'RBC antigen matching'.)
Once these patients produce multiple alloantibodies, it is very difficult to provide compatible blood for transfusion. To avoid this situation, there is a recommendation for hospital blood banks to complete an extended red cell phenotype or genotype with SCD patient's RBCs and to provide prophylactic red cell ABO, Rh, and Kell antigen-matched blood in an effort to prevent alloimmunization [22,23]. (See "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques", section on 'RBC antigen matching'.)
Even though the transfused RBCs are not completely matched with the patient's phenotype, patients rarely become alloimmunized to any RBC antigen when using this approach [24]. However, the mechanism of prevention of all alloantibody production by matching for only certain antigens is not well understood.
Alloantibodies to high frequency antigens — High frequency antigens, such as U, Vel, k, Lu(b), and Yt(a) are present in more than 99.8 percent of the population. If a patient lacks a high frequency antigen, the patient can make an alloantibody against this antigen. Because these antigens are present on almost all donor RBCs, crossmatches will be positive with virtually all randomly selected units of blood. A family history of difficulty in finding compatible blood for transfusion is a valuable clue to this diagnosis.
Identification of antibodies to high frequency antigens requires rare reagent RBCs lacking these antigens. Such reagent RBCs are not available at the average hospital blood bank; a reference laboratory must be consulted in order to identify these rare antibodies. In such cases, significant delays can be expected in securing safe, compatible units of blood for transfusion. For patients with an urgent need for transfusion, blood can be issued under a nonstandard release that is approved by a clinician or as an emergency release. (See "Pretransfusion testing for red blood cell transfusion", section on 'Emergency release blood for life-threatening anemia or bleeding'.)
Delayed hemolytic transfusion reaction — If a recently transfused patient is suspected of active red cell destruction based on clinical symptoms and laboratory parameters consistent with hemolysis and has a positive direct antiglobulin test (DAT, Coombs test), the consideration for delayed hemolytic transfusion reaction should be entertained. If the antibody identification test demonstrates a new alloantibody in the patient's plasma and the same alloantibody is also present in an eluate prepared from the patient's RBCs (figure 1), a diagnosis of delayed hemolytic transfusion reaction (DHTR) can be made and compatible blood can be provided. (See "Hemolytic transfusion reactions", section on 'Delayed hemolytic transfusion reactions and delayed serologic transfusion reactions' and "Pretransfusion testing for red blood cell transfusion".)
Identification of blood for transfusion — The goal of all of the above procedures is to arrive at the proper diagnosis, identify the offending antibody(s) and provide compatible blood for transfusion. Finding compatible blood for patients with multiple RBC alloantibodies or antibodies against high frequency antigens may be very time consuming and is dependent upon the availability of blood lacking the corresponding antigens to which the patient has formed antibodies.
Patients with multiple alloantibodies — For patients with multiple antibodies, finding compatible units can be challenging and depends on the antigen frequency in the donor population [25]. For example, if a patient is Type O RhD negative with anti-K, anti-Jk(b), and anti-Fy(a), in order to find one compatible unit of RBCs (a unit that is K, Jk(b), and Fy(a) negative), the calculated theoretical chance is 0.006, or one out of 167 units (table 2). In these situations, the hospital must work with the community blood center in order to obtain sufficient units of compatible blood for the patient. The blood center may also wish to store frozen units of blood for future transfusion needs of the patient; these can be stored up to 10 years.
Alloantibody to a high frequency antigen — Another difficult-to-transfuse patient is one with an antibody to a high frequency antigen found on the majority of RBCs in the general population. Among these rare antibodies, some are clinically significant and some are not. Tests such as the monocyte monolayer assay (MMA) and the chemiluminescence test have been used in predicting the clinical significance of RBC alloantibodies [26-28].
The MMA is a highly technical and time consuming test. Both tests are only available in reference laboratories. If the alloantibody is not clinically significant, multiple random units can be crossmatched with the patient's plasma. The most compatible units can be safely transfused. If the alloantibody is clinically significant, the following options are available:
●A rare donor file may be contacted for compatible blood, usually via the regional blood center. Identification and delivery of compatible blood may take several days.
●The patient's close family members, especially siblings, may be tested to determine if one or more of them also lack the same RBC antigen in question and may serve as blood donors.
●The patient may serve as his or her own source of fully compatible RBCs by virtue of autologous donations, when the need can be anticipated, such as prior to elective surgery. (See "Surgical blood conservation: Preoperative autologous blood donation".)
AUTOANTIBODIES — There are three types of autoantibodies that may be responsible for causing incompatible crossmatches: warm reactive autoantibodies (usually IgG), cold reactive autoantibodies (usually IgM), and drug-induced autoantibodies [29]. Importantly, no patient with autoantibodies should be denied a lifesaving transfusion because of difficulties in finding compatible blood for transfusion, because such patients are likely to tolerate serologically incompatible blood without significant complications [8,9].
Warm autoimmune hemolytic anemia — Warm autoimmune hemolytic anemia (AIHA) is the most common type of AIHA. In one study, warm AIHA represented 70.3 percent of the cases of AIHA that were encountered [29]. Warm AIHA can be idiopathic or secondary to the presence of an underlying disease, such as a lymphoproliferative, autoimmune, or immune deficiency disorder [30].
In warm AIHA the autoantibody reacts optimally with human RBCs at 37°C and usually is IgG, but rarely may be IgM or IgA. The direct antiglobulin test (DAT, Coombs test) will be positive in patients with AIHA, but this is a nonspecific test that can be positive in as many as 10 percent of hospitalized patients who do not have hemolytic anemia associated with the presence of autoantibodies. The incidence of true AIHA is 1 in 80,000 in most published reports [29]. (See "Warm autoimmune hemolytic anemia (AIHA) in adults", section on 'Diagnosis'.)
Cold agglutinin disease — The autoantibody in cold agglutinin disease (CAD) shows optimal reactivity at 4 to 30ºC and usually is an IgM antibody. The DAT is positive, due to coating of the patient's RBCs with complement components. Patients with this disorder suffer episodic anemia upon exposure to cold. (See "Cold agglutinin disease", section on 'Pathogenesis'.)
Drug-induced AIHA — Drug-induced AIHA shows similar findings in the laboratory as warm AIHA, but the anemia recovers when the implicated drug is discontinued, and may recur if the same drug is readministered [5]. Examples of drugs that may be implicated include methyldopa, procainamide, and fludarabine. (See "Drug-induced hemolytic anemia", section on 'Immune-mediated'.)
AIHA and concurrent alloantibodies — The greatest concern in transfusing patients with AIHA involves detection of concurrent alloantibodies in the patient's plasma [31]. The presence of a masking autoantibody makes alloantibody detection and identification more difficult. As an example of their prevalence in this setting, one study indicated that 31 percent of subjects with a warm autoantibody also had at least one alloantibody.
Several techniques can be used to detect an underlying alloantibody [32-35]. The most powerful test is the autoadsorption method (figure 2) [6,7,10,32]. The autoantibody coating the patient's RBCs is driven off the cells by an elution method. The patient's own eluted RBCs are then mixed with the patient's plasma. These cells will adsorb the autoantibodies from the plasma, but alloantibodies cannot be adsorbed since the patient does not have the corresponding antigen on his or her own RBCs. Mixing is continued multiple times until all of the autoantibody is removed from the plasma. If the patient has an alloantibody, it can now be detected and identified. There are, however, several drawbacks to this method:
●It cannot be used in a recently transfused patient
●The autoantibody may be difficult to adsorb, either because the antibody titer is too high or the patient's RBCs are too fragile for any manipulation
●It is very time consuming
●There is often a requirement for more blood samples from an already anemic patient
When autoadsorption is not possible, an alternate method called allogeneic adsorption is available by using allogeneic RBCs of varying phenotypes to adsorb autoantibody from the patient's plasma, leaving behind the alloantibody, if present, for subsequent identification [6,7,32,35,36]. Details of these methods are beyond the scope of this discussion.
Identification of blood for transfusion — The provision of blood for patients with cold-reacting antibodies may not present a major challenge as long as all testing and crossmatching is performed at 37°C [6,7,9]. However, in warm AIHA the patient has autoantibodies which react at 37°C and are panagglutinins directed against a common RBC antigen present on the patient's and virtually all RBCs. Therefore, it is impossible to provide "crossmatch compatible" blood for these patients. Fortunately, these patients generally tolerate transfusion of such incompatible blood without suffering serious hemolytic reactions [8,9,37].
Although the survival of these transfused RBCs is shortened, it is not significantly different from the survival of the patient's own RBCs. One report, for example, described 53 patients who received blood transfusions because of decompensated AIHA [8]. No patient had a definite increase in hemolysis, even when the transfused RBCs were serologically incompatible.
In an effort to provide the greatest degree of compatibility, there are several approaches the laboratory can take:
●Crossmatch a number of units (10 to 20) and select the most appropriate blood components (ie, among all the crossmatched units, select the units with the weakest positive reactions). This approach is especially useful in the situation where the patient is urgently in need of blood transfusion and no time is available to wait for a complete laboratory workup.
●Phenotype or genotype the patient's RBCs. If the patient's extended RBC phenotype is known, transfusion can be accomplished safely by providing phenotypically matched RBCs [38,39]. In most cases, this information is not available to the blood bank. If phenotyping is to be pursued, this should be done prior to the initial transfusion. Since the patient's RBCs are coated in vivo with autoantibody, techniques such as the EDTA-glycine acid method or chloroquine method need to be employed to dissociate autoantibody from the patient's RBCs before phenotyping. If the patient's extended RBC phenotype is not known, partially phenotypically matched RBCs for Rh and Kell may be provided to reduce the risk of alloimmunization and delayed hemolytic and/or serologic transfusion reactions. Genotyping tests have become available in reference laboratories that can be performed on patients who have had recent transfusion [40]. The genotype provides an extended RBC antigen profile to select antigen-negative RBC units for transfusion. However, these techniques are not available in most hospital blood banks.
●Perform autoadsorption to remove autoantibodies from the patient's plasma and then use the adsorbed plasma to crossmatch donor RBC units. This is the best method for finding a compatible unit of blood (figure 2). (See 'AIHA and concurrent alloantibodies' above.)
In vivo crossmatch — In vivo crossmatch procedures are of historical interest only. These approaches used radiolabeled RBCs or in vivo assessment of hemolysis following a small infusion of RBCs [41,42].
ABO DISCREPANCIES — Even though ABO typing is a simple test with 100 percent accuracy being required, there are occasional difficulties in determining the patient's true ABO type. Such ABO discrepancies may cause positive crossmatches with some or all units of donor blood. Most issues can be resolved after careful laboratory investigation. If the patient is in need of urgent transfusion, type O blood can be safely transfused.
The following are the common causes of ABO discrepancies:
●Type A subgroups – Among all type A patients, 80 percent are type A1 and 20 percent are either type A2 or another subtype of A. Patients who are a subgroup of A can have anti-A1 antibodies that will result in positive crossmatches with A1 donor units. Type O blood should be provided to these patients. DNA-based red cell genotyping may be of value in such cases by providing optimally matched donations [43].
●Acquired B phenotype – When group A patients are infected with certain Gram negative bacteria, bacterial enzymes can remove an N-acetyl group from N-acetylgalactosamine on the red cell surface, resulting in galactosamine that is similar to the group B antigen's terminal galactose. ABO typing will show a weak B antigen on the patient's RBCs with strong anti-B in the plasma (normally type B patients should not have anti-B in their plasma). If the patient's plasma is crossmatched with type B donor units, the results will be incompatible. The patient's RBCs can be correctly typed by acidifying the anti-B typing reagent, which will not recognize this "acquired B antigen" and resolve the problem. (See "Red blood cell antigens and antibodies", section on 'ABO antigens'.)
●Patients who have received ABO mismatched bone marrow or stem cell transplants will have a different ABO type than is indicated in their historical medical records. This causes confusion in ABO typing and can result in positive crossmatches. For example, type O patients who receive stem cell transplants from type A donors will have type A RBCs after engraftment, but may transiently continue to have anti-A in their plasma produced by their residual lymphocytes (normal type A patient should not have anti-A in the plasma). If the patient's plasma is crossmatched against a type A donor unit, a positive result will be obtained. In this case, type O blood should be provided. (See "Donor selection for hematopoietic cell transplantation", section on 'ABO and Rh status'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Transfusion and patient blood management".)
SUMMARY AND RECOMMENDATIONS
●Given the time required to perform red blood cell (RBC) compatibility testing, the severity of the patient's condition determines clinical management during the laboratory evaluation. No patient with autoimmune hemolytic anemia should be denied a lifesaving transfusion because of difficulties in finding compatible blood for transfusion; such patients will tolerate serologically incompatible blood. (See 'Initial evaluation and management' above.)
●Three major clinical situations that may lead to difficulty in providing crossmatch compatible blood include the presence of alloantibodies, autoantibodies reacting with common RBC antigens in immune hemolytic anemia, and ABO discrepancies.
•Alloantibodies can be produced by patients who have been exposed to foreign RBCs by transfusion or pregnancy. Particular difficulty is encountered when such patients form either multiple alloantibodies or an antibody to a high frequency RBC antigen. Finding compatible blood for such patients may be very time consuming and is dependent upon the availability of blood lacking the corresponding antigens to which the patient has formed antibodies. (See 'Alloantibodies' above.)
•Autoantibodies can be produced in patients with warm reactive autoantibodies (usually IgG), cold reactive autoantibodies (usually IgM), and drug-induced autoantibodies. The greatest concern in transfusing patients with such autoantibodies involves detection of concurrent alloantibodies in the patient's plasma. (See 'Autoantibodies' above.)
•ABO discrepancies can occur in patients with type A subgroups, in group A patients infected with Gram negative bacteria, and following ABO mismatched hematopoietic cell transplantation. (See 'ABO discrepancies' above.)
ACKNOWLEDGMENTS — We are saddened by the death of Dennis Goldfinger, MD, who passed away in September 2021. The UpToDate editorial staff acknowledges Dr. Goldfinger's past work for many years as an author for this topic.
The UpToDate editorial staff also acknowledges extensive contributions of Arthur J Silvergleid, MD to earlier versions of this topic review.
UpToDate also acknowledges Qun Lu, MD, who contributed to earlier versions of this topic review.
