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1710 Part XI Transfusion Medicine
Nevertheless, mouse models provide a molecular view of the disease TABLE
pathogenesis and generate many new hypotheses to further elucidate 111.4 Alternatives to Standard Allogeneic Transfusions
the mechanism of red cell alloimmunization.
Hemodilution
Intraoperative autologous transfusion
Red Blood Cell Alloimmunization Mitigation Strategies Perioperative blood salvage
Lower transfusion trigger
Blood transfusion is one of the most common therapies provided in Pharmacologic therapies
a hospital, and millions of blood products are transfused every year Pathogen inactivation
worldwide. Therefore, a carefully planned strategy to prevent red cell Red Cell Substitutes
alloimmunization is urgently needed. Reducing red cell alloimmuni- Stem cell derived RBCs
zation can occur in three areas: blood collection/manufacturing,
hospital transfusion services, and through patient care. At the blood
center, prestorage leukoreduction can effectively remove more than
99.99% of the original WBCs. This process minimizes the inflam- all require significant planning. Only virally inactivated components
matory or “danger” signals infused into recipients at the time of and red cell substitutes (both of which are still works in progress)
foreign red cell antigen exposure and thus may reduce subsequent would be available for unanticipated transfusion needs.
alloimmunization. Some blood centers have also begun to provide
non-ABO red cell antigen typing on RBC units to minimize transfus-
ing RBCs with mismatched red cell antigens. Clinical interventions Autologous Blood Transfusion
have also been proposed to reduce red cell alloimmunization risk.
Surgical splenectomy was shown in mouse models and observed in Advantages of Autologous Blood Transfusion
transfusion-dependent patients (e.g., thalassemia) to reduce the
alloimmunization rate; however, this procedure is not as effective if The substitution of autologous blood components for those collected
the initial antigen exposure occurred prior to spleen removal. Since from other (allogeneic) donors eliminates transfusion-transmitted
sickle cell patients develop asplenia at early ages, this finding may also diseases such as viral hepatitis and acquired immunodeficiency syn-
not be relevant to the high incidence of alloimmunization in sickle drome. Immunologic complications related to the transfusion of
cell anemia. Immunosuppression can also theoretically retard the red foreign cells, including hemolysis and febrile reactions to WBCs, are
cell alloimmunization rate. However, one must consider the adverse also prevented. Other advantages, though possible, are less clearly
clinical impact of these drugs. More studies on drug types and dosages established. For example, erythropoiesis may be sufficiently stimu-
are needed to refine this strategy. Finally, blood bank practice plays lated in the repeatedly bled autologous donor to hasten recovery from
a daily pivotal role in preventing red cell alloimmunization in hospital postoperative anemia. Intraoperatively salvaged red cells are spared
patients. Molecular/genetic typing can permit red cell antigen match- the acquired membrane defects (“storage lesion”) and 2,3-DPG
ing at a higher resolution and precision than traditional serologic red deficiencies of refrigerated red cells.
cell antigen typing. This additional testing is particularly helpful in An important drawback to these techniques is their increased
patients with hemoglobinopathies or high titer warm autoantibodies, expense in contrast to the simpler allogeneic transfusions they replace.
who are especially vulnerable to red cell alloantibody formation. In In addition, the availability of autologous components may result in
the current climate of medical care, patients often do not receive care their use in situations where transfusion might not have otherwise
at the same institution; therefore blood bank results may not fully been considered. Patients with suboptimal compensatory erythropoi-
and accurately transfer between hospitals. Recently, the National esis and donation-induced anemia at the time of surgery are also more
Patient Antibody Registry was developed to address this issue. By likely to be given transfusions. Based upon the current level of viral
integrating patient test results from hospital blood banks and blood safety in blood components in the developed world, the use of
centers within a region or across the nation, this shared database not autologous blood has dropped significantly from times when viral
only reduces blood issuing time, but can also facilitate the selection testing was not available or reliable.
of antigen-matched RBCs to prevent or mitigate alloimmunization.
Collectively, the approaches described above to reduce alloimmuniza-
tion were derived from clinical trials, observational studies, and Preoperative Autologous Blood Collection
studies using mouse-models. As many of these approaches incur
additional cost and effort, a validated cost-effective strategy is needed The typical volunteer allogeneic blood donor is allowed to give one
to further improve patient care and reduce red cell alloimmunization. unit of blood no more than once every 8 weeks, to prevent iron
In view of the high costs of finding antigen negative blood and the deficiency. However, provided that bone marrow erythropoiesis can
fact that many patients with sickle cell anemia do not become alloim- be stimulated and satisfactory iron supplies maintained, blood can be
munized, another strategy that remains reasonable until antigen collected as frequently as once a week from an autologous donor.
negative blood becomes more cost effective is to monitor patients Although the shelf-life of refrigerated RBCs is limited to 42 days,
carefully and switch to antigen matching after the first detection of frozen storage for up to 10 years is possible at less than 65°C using
a red cell antibody glycerol as a cryopreservative.
From a cardiovascular standpoint, phlebotomy is well tolerated by
ALTERNATIVES TO ALLOGENEIC RED a variety of seemingly high-risk donors, including the elderly, chil-
dren, pregnant women, and patients with coronary artery disease. By
CELL TRANSFUSIONS contrast, anemia frequently develops during the donation interval
and limits the number of autologous units that can be collected. In
There are many alternatives to standard allogeneic red cell transfu- addition to marginal iron stores, erythropoietin levels often do not
sions for a patient requiring elective surgery (Table 111.4). Potential increase during the donation interval, probably because the hemato-
alternatives include banking autologous units before the surgery, crit level of most donors is not allowed to fall to less than 30%. This
acute normovolemic hemodilution, pharmacologic therapies (i.e., situation may be improved by the administration of the recombinant
erythropoietin or fibrinolysis inhibitors), perioperative salvage, virally growth hormone erythropoietin to autologous donors. The use of
inactivated donor red cells, or blood substitutes. All current options preoperatively donated autologous blood has also been reported for
have their own unique benefits and drawbacks, and some of these a variety of surgical procedures, including radical prostatectomy;
alternatives are not yet available. In cases where an emergency transfu- hysterectomies and other gynecologic procedures; colorectal, biliary,
sion is needed, the first three options would not be possible as they and gastric surgery; orthopedic surgery, and neurosurgery. Since

