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2376 Part XIII: Transfusion Medicine Chapter 138: Blood Procurement and Red Cell Transfusion 2377
DELAYED TRANSFUSION REACTIONS RBC, platelet, and granulocyte units all contain some lymphocytes
Delayed Hemolytic Transfusion Reactions and therefore carry a risk of TA-GVHD; plasma and cryoprecipitate
are acellular and therefore pose no risk. To prevent TA-GVHD, lym-
DHTRs occur when a previously immunized patient receives red cells phocytes within a blood component must be eliminated or disabled.
containing the corresponding antigen but are compatible in the cross- Leukoreduction is not sufficient, as it reduces, but does not completely
match because of a low titer of circulating alloantibody. DHTRs occur eliminate white blood cells. Frozen units may also carry a risk, as the
in 0.2 to 2.6 percent of patients. It is vanishingly rare in infants younger lymphocytes may survive. Gamma and X-ray irradiation of components
than 4 months of age, and more common in chronically transfused are effective prophylaxis for TA-GVHD. A dose of at least 2500 cen-
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patients. tigray to the center of a cellular blood component and 1500 centigray
Approximately 30 to 40 percent of alloantibodies become unde- throughout the unit leaves lymphocytes intact but unable to proliferate.
tectable months to years after their initial identification. However, a This simple precaution prevents TA-GVHD.
patient previously immunized by transfusion or pregnancy may develop Irradiation at the indicated dose appears to damage the red cell
a secondary immune response after reexposure to a blood group anti- membrane. The damage does not affect the oxygen carrying capacity of
gen. Decreasing Hct or failure to see the typical 1 g/dL Hgb/3 percent the erythrocyte, but does allow potassium to leak from the cell. The level
Hct increment following transfusion may be noted within several days of extracellular potassium has been shown to increase with storage time.
to weeks of a blood transfusion, as well as an unexplained fever. Hemo- As a result, red cells may be stored for only 28 days after irradiation.
lysis from DHTR is typically extravascular, without dramatic clinical
symptoms and signs, although some classes of IgG bind complement
and will cause intravascular hemolysis. Hemolysis in DHTRs is usually POTENTIAL EFFECT OF AGE OF RED
mild and gradual, however, when antibodies are produced against anti-
gens in the Kidd blood system, the hemolysis may be rapid, intravascu- CELLS ON TRANSFUSION OUTCOME
lar, and may be severe.
The usual evidence of hemolysis is seen. The appearance of sphero- In the United States, RBC may be stored in additive solution for up to
cytes and reticulocytes on peripheral blood film, increases in total and 42 days. The criteria used to determine storage limits are based on in
unconjugated bilirubin, and increased LDH. The DAT is usually posi- vivo recovery and in vitro hemolysis data. During storage, RBC units
tive but may be negative if all the transfused RBCs have been eliminated develop a progressive “storage lesion.” Some of these changes include
from the circulation. The antibody screen is usually positive and the an increase in free Hgb which acts as a nitric oxide scavenger; a reduc-
antibody can be identified. No specific management is usually needed tion in 2,3-bisphophosglyceric acid (2,3-BPG), which leads to increased
as these reactions are usually subtle and clinically silent. In cases of oxygen affinity/decreased oxygen delivery; an increase in hydrogen ions
intravascular hemolysis, clinical support measures are similar to those in the supernatant causing a drop in the pH; an increase in microvesi-
described for an acute hemolytic transfusion reaction. If transfusion cles in the supernatant, creating a procoagulant effect and reduced RBC
is necessary donor red cells negative for the offending antigen may be membrane deformability. Each of these changes is a dynamic process,
selected. with some occurring on the first day of blood storage, and others taking
days or weeks to be evident. Aspects of the storage lesion have been
demonstrated in vivo using healthy volunteers who are transfused with
Posttransfusion Purpura autologous units that are stored for widely divergent time periods. In
Posttransfusion purpura is a rare immune-mediated disorder that is dis- three of these controlled experiments, no differences were found in
cussed in greater detail in Chap. 139. pulmonary function, nitric oxide-mediated hyperemic response to
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ischemia, or cognitive function. A fourth volunteer study found sig-
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nificant differences with in vivo iron-related parameters and signs of
IRON OVERLOAD hemolysis when fresh and older units were compared. 82
The clinical relevance of these in vitro and in vivo studies is not
One of the most common complications of chronic RBCs transfusion is clear. Some of the in vitro findings are reversed within 24 to 48 hours of
iron overload, which is further discussed in the chapters on congenital transfusion, and no adverse effects were reported in the volunteers used
hemoglobinopathies (Chaps. 48 and 49). for the in vivo studies; however, they were healthy and may be more able
to withstand insults to their system. Multiple retrospective and prospec-
tive studies have looked for an association between the storage age of a
TRANSFUSION-ASSOCIATED RBC unit and clinical outcomes. In one study, in more than 5000 car-
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GRAFT-VERSUS-HOST DISEASE diac surgery patients receiving more than 18,000 units of RBCs, patients
receiving blood that was stored for longer than 2 weeks were at a signifi-
Most cases of TA-GVHD are associated with HSCT. TA-GVHD is a very cantly higher risk of postoperative complications as well as short-term
rare complication that occurs when a susceptible patient is exposed to and long-term survival. Subsequently, a large number of retrospective
viable lymphocytes introduced in a blood transfusion. This can occur studies and a smaller number of prospective studies were performed. A
when transfusions from close relatives or other unintentionally genet- recent review summarizing the findings of 32 studies reported that 18
ically matched donors are administered to severely immunocompro- found a detrimental effect from prolonged RBC storage, while 14 stud-
mised recipients. The immunocompromised recipient is incapable of ies did not. 84,85 It is notable that the four prospective randomized trials
“rejecting” or mounting an attack against the lymphocytes in the trans- included in the review found no significant ill effect. A meta-analysis of
fused blood. In addition, cases of TA-GVHD have been reported in 21 studies, either observational studies or randomized controlled trials,
recipients with an intact immune system. 76,77 found that use of older stored blood is associated with a significantly
TA-GVHD may present with maculopapular rash, fever, watery increased risk of death. 85
diarrhea, liver dysfunction, and marrow failure within 8 to 10 days of The question of higher risk from transfusion of older units con-
transfusion. The mortality rate in is approximately 90 percent and the tinues to be studied in multiple, large prospective clinical trials. These
downhill course often rapid. studies are being conducted with ICU and cardiac surgery patients,
Kaushansky_chapter 138_p2365-2380.indd 2377 9/18/15 11:14 AM

