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p > 0.05: When compared to after induction of anesthesia and before transfusion values (within group analysis).
p > 0.05: When compared to before and after transfusion values (within group analysis).
#
p > 0.05: Between the groups.
B. Ayhan et al. / Transfusion and Apheresis Science 49 (2013) 212222 217
by higher levels of hemolysis, methemoglobin and lipid
peroxidation. In our daily practice, during preparation of
blood, RBCs were tested for osmotic fragility by our insti-
tute blood bank because of these effects of TGAM solution.
Therefore, we thought that using RBCs in TGAM additive
solution could not be inuenced our study results.
All data are presented as meanSD. TX: Transfusion
*p<0.001: When compared to baseline and before TX values in Group A (within group analysis)
**p<0.001:When compared to before and after TX values in Group A (within group analysis)
#p<0.001: When compared to baseline and before TX values in Group B (within group analysis)
##p>0.01: When compared to before and after TX values in Group B (within group analysis)
p<0.001: After TX, between the groups
Fig. 2. Changes in FCD values between time points.
All data are presented as meanSD. TX: Transfusion
*p<0.01: When compared to baseline and before TX values in Group A (within group analysis)
**p>0.05:When compared to before and after TX values in Group A (within group analysis)
#p<0.05: When compared to baseline and before TX values in Group B (within group analysis)
##p>0.05: When compared to before TX and after TX values in Group B (within group analysis)
p>0.05: After TX, between the groups
Fig. 3a. Changes in MFI values in small-sized vessels between time points.
218 B. Ayhan et al. / Transfusion and Apheresis Science 49 (2013) 212222
We compared blood stored for more than 21 days
against blood stored for less than 7 days in our study; ret-
rospective analysis has determined that a number of units
older than 21 days is an independent risk factor for multi-
ple organ failure [45].
There are conicting data on whether transfusion of old
or fresh RBCs increases tissue oxygenation because accu-
mulating evidence is showing that there can be a negative
relationship between the storage time and RBCs function.
Van Bommel et al. [46], using a rat haemorrhagic shock
model, evaluated the effect of RBC storage lesion on oxy-
gen delivery. They have found that transfusion of RBCs
stored for 28 days did not restore the microcirculatory oxy-
genation. Chin-Yee et al. [47] have also observed that old
(7 days storage) RBCs adhered to the vessel walls to signif-
icantly greater degree than the fresher cells (less than 24 h
of storage). Raat et al. [13] used human blood for transfu-
sion and they showed that old blood (56 weeks storage)
resulted in a 25% decrease in rats intestinal microvascular
oxygenation after transfusion, and it was not observed
with fresh blood (26 days). Collins and Stechenberg [48]
have studied the effect of the exchange transfusion of
90% of the original RBC mass in rats with blood stored
1 day or 1420 days to nal Hct of 36% (normal), 28%
(moderate anemia) and 17% (severe anemia). They have
found that survival being lower only for the rats transfused
with old RBCs at low Hct. In our study, although there were
no differences both pre-transfusion and post-transfusion
Hct levels in the between two groups, in the fresh blood
group, blood transfusion increased FCD and FCD remained
unaffected in the old blood group. And also, we found that
Hb values were different between the two groups after the
transfusion. In the old blood group, while post-transfusion
Hb levels were higher than the other group, FCD was not
affected. Windsant et al. [49] have demonstrated that pro-
longed storage signicantly increased free Hb concentra-
tions transiently and nitric oxide (NO) consumption.
Development of hemolysis during storage might contrib-
ute to release of free hemoglobin and a nitric oxide (NO)
scavenger. This may impair microcirculatory perfusion
after transfusion with old blood. Therefore, in our study,
FCD could not affected from blood transfusion in the old
blood group.
We know that decreased or remained FCD is related
with lowered perfusion pressure and observed with ische-
miareperfusion injury which has the complication of oxi-
dative stress [50]. On the other hand, Van der Lindan et al.
[51] demonstrated that fresh RBC transfusion and in-
creased blood ow (pump ow) are equally effective in
restoring tissue oxygenation in anaesthetized dogs under-
going cardiopulmonary bypass. These experimental stud-
ies conclude that fresh blood is a better resuscitation
uid than older [52,53]. But, unfortunately, experimental
studies in animal species have interspecies differences in
RBC metabolism and structure, therefore they do not fully
reproduce clinical conditions or replicate human
physiology.
Some of the prospective and retrospective studies that
evaluate the effect of RBC storage on patient outcomes in
cardiac surgery, trauma, and critical care [5457]. These
studies found mixed results with some showing worse out-
comes in patients who received older RBCs, whereas others
showed no difference. Kiraly et al. [58] have been exam-
ined the effect of the age of the blood transfused on the tis-
All data are presented as meanSD. TX: Transfusion.
*p>0.05: When compared to baseline and before TX values in Group A (within group analysis)
**p>0.05:When compared to before and after TX values in Group A (within group analysis)
#p>0.05: When compared to baseline and before TX values in Group B (within group analysis)
##p>0.05: When compared to before TX and after TX values in Group B (within group analysis)
p>0.05: After TX, between the groups
Fig. 3b. Changes in MFI values in medium-sized vessels between time points.
B. Ayhan et al. / Transfusion and Apheresis Science 49 (2013) 212222 219
sue oxygenation using near infrared spectroscopy in thirty-
two critically injured trauma patients. In this study, they
dened old blood as blood stored for 21 days or greater
and new blood as blood stored for less than 21 days.
They found that older RBCs decreased in peripheral tissue
oxygenation. On the other hand, Weiskopf et al. [59]
showed that erythrocytes stored for 3 weeks have similar
effects as erythrocytes stored for 3.5 h in reversing the
neurocognitive decit of acute anemia in nine healthy vol-
unteers donated. In addition most of the studies on blood
bankinginduced alterations in RBC ow properties have
shown that routine cold storage is associated with
reduction in RBC deformability [60], increased RBC ow,
elevation of their adherence to endothelial cells [61,62]
and increased aggregability [63]. Actually, if patients had
lower hematocrit, it may have improved microvascular
ow. In our study; while microvascular ow index (MFI)
remained unaffected in both groups, blood transfusion in-
creased FCD in only the fresh blood group. In addition,
there were no differences between the Hct values for both
groups. According to these results; RBC ow properties did
not effect from storage in our study.
We used RBCs that were prepared with the routine stor-
age procedures of our Faculty of University Blood Bank,
specically non-leukoreduced. Most studies have showed
that removal of white blood cells reduces storage-induced
damage to RBCs [6468]. The presence of leukocytes in
transfused blood may play an important role in quality of
transfused erythrocytes and responsible for the transmis-
sion of blood-borne infections. It is generally accepted that
universal leukocyte depletion include a reduction in the
incidence of non-hemolytic transfusion reactions, immu-
nosuppression [69], and mortality. On the other hand,
Weinberg et al. [57]. have been demonstrated that a mor-
tality association with older blood (>14 days) despite uni-
versal leukoreduction and leukoreduction on mortality is
doubtful. Nathens et al. [70] compared 1864 injured pa-
tients to receive leukoreduced versus standard non-leuko-
reduced transfusions during the hospitalization. They have
found that no difference in mortality or infectious morbid-
ity in the 268 patients. But, they did not evaluate the age of
transfused blood in their study design. Similarly, Englehart
et al. [71] showed that the use of leukoreduction blood
does not improve outcome in trauma patients. In our
study, we used non-leukoreduced blood transfusion in
our patients. To our study results, we thought that the
age of blood could be more important than the presence
of leukocytes in RBCs on microcirculation.
Our study has its limitations. First, we investigated a
relatively small number of patients so that we may have
missed minor differences attributable to measurements.
Second, we included patients who underwent different
kind of surgery that may have different microcirculation
properties. Lastly, we did not correlate microcirculation
parameters with any clinical outcome parameters like
long-term survival or morbidity and mortality rate in our
study.
In summary, we showed that the microvascular effects
of RBC transfusions are quite variable and are correlated
with the age of the transfused RBCs in major surgical pa-
tients. These effects cannot be predicted from systemic
hemodynamics or systemic blood parameters like Hb and
Hct variables. The risks and benets of RBC transfusion
should be assessed for every patient before transfusion
during major operation. These results will need to be
tested in selected populations under same kind of major
surgery that have similar microcirculation characteristics.
Acknowledgments
The authors would like to thank Academic Medical
Center in Amsterdam in Netherlands and Hacettepe Uni-
versity, Faculty of Medicine, Dept. of Anesthesiology and
Reanimation in Ankara in Turkey.
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