Page 1928 - Hematology_ Basic Principles and Practice ( PDFDrive )

1708 Part XI Transfusion Medicine

since they may receive units returned from smaller community 28 days. The definitions of age have not been based on either clinical
centers who did not expect to use them before their outdate. Hospitals or microcirculatory relevance or related to the feasibility and practi-
that have blood refrigerators outside the blood bank tend to age units cality of blood collection. Most studies have been designed for con-
in the refrigerators because it is cumbersome to rotate the units out venience and feasibility; a red cell storage age study with a definition
frequently. Hospitals with high crossmatched to transfused ratios also of an older RBC unit as greater than 14 days of storage is achievable
tend to have older units on their shelves. given current hospital inventories. Fourteen days is close to the
average age of RBCs stored in a blood bank, but from a blood col-
lection and inventory management perspective, an expiration time of
Red Blood Cell Storage Lesion 14 days would be disastrous for both hospitals and blood collection
facilities. Authorities have argued that studies should be designed to
The RBC storage lesion includes all the changes that occur to blood measure storage age differences between lengths of storage that would
components during blood bank storage. The lesion includes bio- actually be achievable given current inventory levels and difficulties
chemical and structural changes to the red cell, as well as changes in donor recruiting.
that occur in the storage supernatant. The structural changes include Published studies have focused on three patient groups that
red cell membrane loss that leads to the reversible evolution of the consume large numbers of RBC components: cardiac surgery, trauma,
shape of the red cell from a biconcave disc to a spheroechinocyte. and critical care patients. A publication on the effect of RBC storage
After this stage, further red cell membrane loss becomes irreversible, age on hematopoietic transplant recipients has also been recently
and microvesicles are produced. Red cell vesicles are quickly cleared published.
by macrophages due to exposed negatively charged lipids. The infu- The Age of RBCs in Premature Infants study, a double-blinded
sion of a large amount of red cell vesicles during a RBC transfusion study evaluating the effectiveness of RBCs stored no longer than
may overwhelm the reticuloendothelial system and cause a proinflam- seven days versus standard-issue RBCs in 377 neonates requiring
matory and prothrombotic response. The shape changes are also transfusions has been published. The primary outcome revealed that
associated with a rheologic effect, including increased viscosity and using fresh blood of less than 7 days old did not improve the clinical
reduced flow within the capillaries, leading to decreased tissue perfu- outcome of these vulnerable premature infants. Recently, the Red
sion. Many of the biochemical and structural changes, aside from Cell Storage Duration Study evaluated 1098 patients undergoing
vesiculation, are reversible when the RBCs enter human circulation complex cardiac surgical procedures who were likely to require RBC
where pH, ATP levels, and 2,3 DPG levels are normal. transfusion. Patients were randomized to receive RBC units stored
Older red cells become more susceptible to oxidative damage, for either 10 or fewer days or 21 or more days. The median storage
although this change generally occurs at a lower rate during in vitro times of the transfused RBCs were 7 days versus 28 days for the two
conditions than in vivo due to the lower storage temperature. groups. RBC storage duration was not associated with a change in
However, during a transfusion the human circulation is confronted the Multiple Organ Dysfunction Score (MODS) or the 28-day
by a bolus of equally damaged RBCs that may overwhelm the reticu- mortality. Adverse events did not differ between the groups, except
loendothelial system. The work of Hod and Spitalnik emphasized that hyperbilirubinemia was more common in the older storage age
that up to 25% of transfused RBCs with prolonged storage are cleared group.
within 24 hours. The rate of delivery of heme-iron to the reticuloen- The Age of Blood Evaluation study investigated the effect of
dothelial system may abruptly increase as much as 60-fold after leukoreduced RBCs stored 7 days or less versus leukoreduced
transfusion of even a single unit of RBCs. This can surpass the rate standard-issue RBCs on 90-day all-cause mortality. Investigators
of uptake by transferrin and produce circulating nontransferrin enrolled 2430 adult participants receiving their first RBC unit in an
bound iron that may in turn lead to the myriad of problems associ- intensive care unit. The study found that fresh versus standard-issue
ated with iron overload. red cells did not decrease 90-day mortality among critically ill adults.
Irradiated cells are exposed to additional oxidative stress that can Most recently, the Age of Blood in Children in Pediatric Intensive
damage red cell protein and lipid. WBCs in the component also break Care Units trial has been initiated to examine the effect of transfusing
down during storage and release proteases and lipases. Lysophospho- less than 7-day old blood (versus standard-issue age) in over 1500
lipids and glycosidases are produced. Glycosidases may remove sialic pediatric ICU patients requiring transfusion. The primary outcome
acid and other sugars from the red cell membrane and can cause is new or progressive MODS.
increased binding of stored red cells to endothelial cells and poten- Although the randomized prospective trial seems to be the only
tially contribute to endothelial inflammation. Increased lysophospho- option to determine the clinical consequences of the RBC storage
lipids, such as platelet activating factor, have been found in units that lesion, conducting a well-designed trial is not an easy task. Limited
have caused TRALI. blood bank inventories to supply the longer and shorter storage
duration arms, difficulty in consenting patients, and difficulty in
selecting outcome measures to study have made creating the ideal
Clinical Relevance of the Red Cell Storage Lesion study a formidable challenge.
The published studies evaluating whether adverse clinical conse-
Retrospective or prospective observational studies in many diverse quences are associated with prolonged RBC storage have yet to sat-
patient populations have suggested numerous adverse events that may isfactorily answer this important question in all patient populations.
be associated with prolonged RBC storage, including increased risk The current RBC inventory almost always meets hospital needs with
for mortality, postoperative infection, multiorgan failure, deep venous a 42 day RBC expiration period but is not currently equipped to
thrombosis, or increased length of stay in the ICU or hospital. The meet the needs of a less than 7 day inventory, or even a less than 21
observational studies on this topic have a number of significant limi- day inventory. Although it is logical to expect that there is a limit to
tations. First, larger volumes of RBC transfusion predict worse out- RBC storage, beyond which the risks of transfusion outweigh the
comes. Patients who are transfused larger volumes are statistically benefits of transfusion, none of the randomized studies described
more likely to receive older RBCs. Second, confounding factors may above is designed to determine this limit.
not be recognized and, as a result, are discounted in nonrandomized Animal studies have been able to provide additional information
studies. Third, individual methodologies in the presently available about the safety of RBCs stored for longer amounts of time than the
studies have varied markedly. Some studies have looked at the effect clinical trials in humans. Natanson et al found that older blood (42
of mean storage age of all units transfused on outcome and some have days of storage) increases the risk of transfusion (survival and multiple
broken storage time into categorical groups (i.e., is storage less than organ injury) in canine subjects with infection. In addition, in criti-
14 days safer than storage beyond 14 days). In addition, studies have cally ill dogs with infection, they showed a favorable risk-to-benefit
not used a single definition for “older” units; some have defined older ratio for washing older blood. However, fresh blood (7 days of
units as greater than 14 days, greater than 21 days, or greater than storage) was superior to older blood, whether washed or not.