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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
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