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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
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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
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phocyte count is greater than 1 × 10 /L; however, if chronic GVHD is capillary permeability and arteriolar dilatation causing a fall in systemic
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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
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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
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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-
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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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