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2374           Part XIII:  Transfusion Medicine                                                                                                               Chapter 138:  Blood Procurement and Red Cell Transfusion           2375




               Maintaining graft-versus-host disease (GVHD) prophylaxis with only a     ADVERSE EFFECTS OF RED CELL
               T-cell inhibitor, such as cyclosporine, without an accompanying B-cell
               inhibitor, is also considered a risk factor.              TRANSFUSIONS
                                                                      The precise risk of an adverse reaction is difficult to estimate; many reac-
               Transfusion-Transmitted Cytomegalovirus                tions may be wrongly attributed to the patient’s underlying illness, and
               CMV infection continues to be a serious complication following   approximately half of all transfusions are given to anesthetized patients
               HSCTs. Most CMV infections are likely the result of reactivation of   in the operating rooms where reactions may be blunted or more difficult
               virus from a previous infection rather than acquisition of a new strain.   to recognize. The incidence of some adverse reactions has fallen in the
               However, in CMV-antibody–negative patients there is a risk of devel-  past decade due to changes in component handling. Adverse reactions
               oping a transfusion-transmitted de novo CMV infection. To reduce   may occur soon after a transfusion begins, as seen with acute hemolytic
               this risk, one may use CMV-antibody-negative blood, or leukocyte-   reactions or acute lung injury, or within days to weeks of a transfusion,
               reduced components. A large controlled trial and a meta-analysis   as seen with delayed hemolytic reactions.  Fortunately, the majority
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               from 2007 showed that leukocyte-reduced components are as effec-  of acute transfusion reactions are mild and manageable. Many of the
               tive as antibody-negative components in preventing transfusion-   reported transfusion-related fatalities involve human errors which may
               transmitted CMV. 46,47  Two additional studies support the safety of using   be as much as 1:18,000 transfusions.
               only   leukoreduced blood in preventing transfusion transmission of
               CMV. 48,49  Both studies found 0 percent risk of transfusion-transmitted
               CMV infection. Nonetheless, the overall risk of transfusion transmis-  IMMEDIATE TRANSFUSION REACTIONS
               sion of CMV in leukoreduced components is not zero. CMV DNA was   In general, immediate transfusion reactions are more dangerous than
               found in 44 percent of newly seropositive blood donors, and the over-  delayed reactions. Severe complications, including death, can on rare
               all prevalence of CMV DNA was 0.13 percent in nearly 32,000 dona-  occasions develop within a few minutes of initiating transfusion. Close
                   50
               tions.  While blood products could be obtained from donors with   attention and early vital sign assessments are recommended at the
               a longstanding history of CMV-positive serology, a more practical   beginning and within 15 minutes of starting a transfusion.
               approach is to screen donated blood for CMV DNA or immunoglobu-
               lin (Ig) M antibodies, although we believe that the use of leukoreduced   Acute Hemolytic Transfusion Reactions
               blood components is adequate.                          Acute hemolytic transfusion reactions (AHTRs) are almost always
                                                                      caused by the immune-mediated destruction of ABO-incompatible
               Transfusion-Associated Graft-Versus-Host Disease       transfused blood. ABO incompatible transfusions are estimated to occur
               All HSCT patients should receive irradiated components from the time   in one in 38,000 to one in 70,000 RBC transfusions.  Isohemagglutinins
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               of initiation of conditioning chemotherapy, and for at least 1 year fol-  can activate the complement and coagulation systems. C3a and C5a can
               lowing transplantation to prevent TA-GVHD. However, many centers   activate white blood cells to release inflammatory cytokines (interleukin
               continue to provide irradiated products for the life of the patient. The   [IL]-1, IL-6, IL-8, and tumor necrosis factor-alpha [TNF-α]), contribut-
               British Committee for Standards in Haematology (BCSH) recommends   ing to fever, hypotension, wheezing, chest pain, nausea, and vomiting.
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               that allogeneic transplant recipients should receive irradiated com-  The presence of antigen-antibody complexes and activated complement
               ponents for 6 months posttransplantation, or until the patient’s lym-  on donor RBCs may lead to bradykinin generation. This can increase
                                          9
               phocyte count is greater than 1 × 10 /L; however, if chronic GVHD is   capillary permeability and arteriolar dilatation causing a fall in systemic
                                                            51
               present, then irradiated products should be given indefinitely.  Autol-  blood pressure. Activation of factor XII may initiate the coagulation
               ogous transplant patients should begin receiving irradiated compo-  cascade with formation of thrombin and lead to disseminated intravas-
               nents from the time of initiation of conditioning chemotherapy, but can   cular coagulation. Renal failure may also develop as a result of ischemia,
               revert to nonirradiated components 3 months after the transplantation.   hypotension, antigen-antibody complex deposition, and thrombosis.
               If autologous transplant patients received total-body irradiation, then   Although rare, AHTRs can also be seen because of other blood group
               the BCSH recommends extending the use of irradiated products for 6   antibodies, particularly those in the Kidd blood group system.
               months after the transplantation.                          Clinical Presentation  The most common presenting symptom is
                                                                      fever with or without chills or rigors. In mild cases, this may be accom-
                  SOLID-ORGAN TRANSPLANT                              panied with abdominal, chest, flank, or back pain, whereas dyspnea,
                                                                      hypotension, hemoglobinuria, and eventually shock can be seen in severe
               Patients awaiting a solid-organ transplant should have minimal expo-  cases.  Bleeding,  caused  by  the  consumptive  coagulopathy,  can  occur.
               sure to allogeneic blood products to reduce the risk of alloimmuniza-  Hematuria can be the first sign of intravascular hemolysis, particularly in
               tion. Leukoreduced components contain sufficient white blood cells   anesthetized or unconscious patients. The severity of AHTR is extremely
               to immunize a patient against class I and class II HLA molecules. The   variable and usually depends on the rate and total volume of blood
               risk of sensitization from a blood transfusion ranges from 2 to 21   administered. Approximately 47 percent of the recipients of ABO incom-
               percent.  Sensitization may increase the extent of alloimmunization,   patible blood show no effects, even after receiving a whole unit, 41 percent
                     52
               which contributes to delays in finding a compatible organ for trans-  show symptoms of AHTR, and mortality is approximately 2 percent. 55,56
               plantation. In fact, patients who have been transfused have an 11 per-  Laboratory Evaluation  Laboratory evaluation involves checking
               cent reduction in the likelihood of ever receiving a renal transplant.    for technical and identification errors, examine a posttransfusion spec-
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               Attempts to reduce alloimmunization by matching blood donors and   imen for hemolysis, and perform a DAT to detect antibody-coated red
               patients  or matching for the DR locus have shown no consistent   cells. If AHTR is strongly suspected, repeat ABO and Rh typing of the
                     53
               reduction.  Using a Hgb of 7 g/dL as a safe threshold for transfusions   patient and the transfused blood and repeat antibody screen and cross-
                       54
               can minimize exposure. In some patients the use of erythropoiesis-  match may be helpful. A negative DAT occurs in rare cases when all
               stimulating agents (ESA) may help decrease the number of RBC trans-  transfused RBCs are lysed.
               fusions; however, ESAs are contraindicated in patients with a history   Management  Immediate discontinuation of transfusion should
               of malignancy or stroke.                               always be the first step in any transfusion reaction. Maintaining vascular






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