Transfusion Of Older Blood Research Articles

Old, older, the oldest: red blood cell storage and the potential harm of using older red blood cell concentrates.

Over the last decades, clinical studies have suggested that transfusion of red blood cells (RBCs) might negatively impact patient outcomes. Even though large randomized clinical trials did not show differences in mortality when transfusing fresh versus standard-issue RBC units, data imply that RBCs at the very end of storage could elicit negative effects. Certain alterations of RBCs during cold storage -- such as an increase of potassium and lactate in the storage solution -- have been discovered a century ago. In recent years, proteomic and metabolomic studies have shed more light into pathophysiological changes of RBCs during storage and have helped to specify the definition of old blood. These advancements are now utilized to increase the quality of stored RBCs and devise therapeutic strategies (e.g. nitric oxide, haptoglobin, or reduction of the iron load) when transfusing old blood. Further research to improve the quality of RBC units and to study populations potentially at risk is warranted. Until the question whether transfusion of old blood is detrimental for specific patient populations has been answered, a deliberate use of RBC transfusion should be implemented.

290. Blood transfusions: does storage duration affect postoperative infection risk?

BACKGROUND CONTEXT In the US, approximately 5-10% of spine surgery patients require postoperative blood transfusions. It is unclear whether or not blood transfusions increase risk of postoperative infections in these patients. Interestingly, while current regulations allow for blood to be stored up to 42 days, recent studies have suggested that prolonged storage may influence postoperative infection risk. PURPOSE The purpose of this study was to compare effects of “old” and “fresh” blood transfusions on infection burden in a mouse model of spine implant infection. METHODS C57BL/6 mice were bled aseptically by cardiac puncture for blood collection. Blood was stored for 12 days (old blood) or 1 day (fresh blood) prior to transfusion (both samples were within acceptable transfusion criteria). To model a spine implant infection in C57BL/6 mice, a stainless-steel wire was surgically placed in the L4 spinous process and inoculated with a bioluminescent strain of Staphylococcus aureus. Mice were transfused immediately postoperatively and on postoperative day (POD) 1 with 200 microliters of either old blood, fresh blood, or no blood (saline). In vivo bioluminescent imaging (BLI) was used to quantify bacterial burden postoperatively. RESULTS All infected mice demonstrated increased BLI compared to sterile controls. On POD3, mice transfused with old and fresh blood had higher average BLI compared to mice who received no blood. On POD7 and POD10, mice transfused with old blood demonstrated higher average BLI than both fresh and no blood groups. CONCLUSIONS Transfusion of old blood in our mouse model of spine implant infection resulted in persistently elevated BLI compared to fresh blood and no blood groups. These findings suggest that storage duration of blood products may indeed increase infection burden and emphasize the need for further research in this area. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Age of transfused red blood cells and health outcomes in two surgical cohorts

RationaleRed blood cells (RBC) undergo morphologic and biochemical changes during storage which may lead to adverse health risks upon transfusion. In prior studies, the effect of RBC age on health outcomes has been conflicting. We designed the study to assess the effects of RBC units’ storage duration on health outcomes specifically for hospitalized patients undergoing hip fracture surgery or coronary artery bypass grafting (CABG) surgery. MethodsUsing International Classification of Diseases (ICD) 9 codes, hip fracture surgery and CABG surgery patients, who received RBC transfusions between 2008 and 2013, were retrospectively identified from the electronic medical records system. Hip fracture surgery and CABG cohorts were sub-divided into 3 blood age groups based upon RBC unit age at the time of transfusion: young blood (RBC units stored less than or equal to 14 days), old blood (RBC units were stored for greater than or equal to 28 days), or mixed blood for the remaining patients. Outcome variables were 30-day, 90-day, and inpatient mortality as well as hospital length of stay. ResultsA total of 3,182 patients were identified: 1,121 with hip fractures and 2,061 with CABG. Transfusion of old blood was associated with higher inpatient mortality in the hip fracture surgery cohort (OR 166.8, 95% CI 1.067-26064.7, p = 0.04) and a higher 30-day mortality in the CABG cohort (OR 4.55, 95% CI 1.01–20.49, p = 0.03). ConclusionsTransfusing RBC units stored for greater than or equal to 28 days may be associated with a higher mortality for patients undergoing hip fracture or CABG.

Transfusion of Older Red Blood Cells Increases the Risk of Acute Kidney Injury After Orthotopic Liver Transplantation: A Propensity Score Analysis.

Acute kidney injury (AKI) is a common and serious complication of orthotopic liver transplantation (OLT). Transfusion of older red blood cells (RBCs) has been implicated in poor outcomes in trauma, cardiac surgery, and critically ill patients. However, whether transfusion of older RBCs plays any role in post-OLT AKI remained unknown. The aim of this study was to investigate the effect of the age of transfused RBCs on post-OLT AKI. The clinical data of consecutive adult patients who received donation after cardiac death and underwent OLT from December 2011 to December 2015 were analyzed. These patients were divided into 2 groups: the newer blood group, who received exclusively RBCs that had been stored for <14 days; and the older blood group, who received RBCs that had been stored for 14 days or more. The incidence of post-OLT AKI, severe AKI, lengths of intensive care unit and hospital stay, and in-hospital mortality after OLT were analyzed. Postoperative AKI occurred in 65.1% of patients in the older blood group and 40.5% of patients in the newer blood group (P < .01). The incidence of severe AKI after OLT was significantly higher, and the duration of intensive care unit stay was significantly longer, in the older blood group. After adjustment by the multivariable regression logistic analysis, transfusion of older blood was independently associated with post-OLT AKI (odds ratio [OR] = 2.47 [95% confidence interval {CI}, 1.13-5.41]; P = .024) and severe AKI (OR = 5.88 [95% CI, 2.06-16.80]; P = .001). After adjustment by the inverse probability of treatment weighting analysis, patients in the older blood group still had significantly higher incidences of postoperative AKI (OR = 2.13 [95% CI, 1.07-4.22]; P = .030) and severe AKI (OR = 3.34 [95% CI, 1.47-7.60]; P = .003) than those in the newer blood group. Transfusion of older RBCs significantly increased the risk of postoperative AKI in liver transplant recipients.

Washing older blood units before transfusion reduces plasma iron and improves outcomes in experimental canine pneumonia

AbstractIn a randomized controlled blinded trial, 2-year-old purpose-bred beagles (n = 24), with Staphylococcus aureus pneumonia, were exchanged-transfused with either 7- or 42-day-old washed or unwashed canine universal donor blood (80 mL/kg in 4 divided doses). Washing red cells (RBC) before transfusion had a significantly different effect on canine survival, multiple organ injury, plasma iron, and cell-free hemoglobin (CFH) levels depending on the age of stored blood (all, P < .05 for interactions). Washing older units of blood improved survival rates, shock score, lung injury, cardiac performance and liver function, and reduced levels of non-transferrin bound iron and plasma labile iron. In contrast, washing fresh blood worsened all these same clinical parameters and increased CFH levels. Our data indicate that transfusion of fresh blood, which results in less hemolysis, CFH, and iron release, is less toxic than transfusion of older blood in critically ill infected subjects. However, washing older blood prevented elevations in plasma circulating iron and improved survival and multiple organ injury in animals with an established pulmonary infection. Our data suggest that fresh blood should not be washed routinely because, in a setting of established infection, washed RBC are prone to release CFH and result in worsened clinical outcomes.

P15: Nitric oxide scavenging by red blood cell microparticles

Cell derived Microparticles (MPs) are small phospholipid vesicles released from a variety of cells, such as platelets, red blood cells (RBCs) and white blood cells, or endothelial cells. Accumulating evidence shows that MPs are involved in many biological diseases. The clinical significance of MPs has been studied for years. Our studies focus on red blood cell MPs that are released during blood storage and post-transfusion. We have reviously shown that these MPs scavenge NO almost as fast as cell free hemoglobin, about 1000 times faster than red cell encapsulated hemoglobin. Reduced NO scavenging by cell-free hemoglobin compared to red cells is due limitations of external diffusion of NO to the red cell (including that through a cell-free zone that forms in the blood vessel pushing the red cells away from the endothelium where NO is made) and by finite red cell membrane permeability of NO. We have now explored the relative role of cell-free hemoglobin and hemoglobin encapsulated in microparticles formed during blood storage in scavenging NO. We have measured the NO consuming ability of free HbA and MPs in plasma of different age stored blood using a chemiluminescence-based assay. Our results show that both hemoglobin concentrations of free HbA and MPs increase along with blood aging. The proportion of hemoglobin concentration in MPs increases compared to cell-free hemoglobin as the blood ages. To explore the extent of NO scavenging by MP-encapsulated hemoglobin (MP-HbA) during blood transfusion, we have also modeled Nitric Oxide (NO) uptake by RBCs and MPs within a blood vessel using computer simulations. We found that membrane permeability appears to influence the rate of NO uptake by RBCs and MPs. In addition, the appearance of MPs in RBC cell free zone may significantly reduce NO bioavailability. To determine whether MPs do enter the cell-free zone, we have studied the effect of MPs on NO-mediated vasodilation with and without intravascular flow by using isolated micro vessels in a myograph apparatus. The data show that, similar to the case of cell-free hemoglobin and dissimilar to the case of red blood cells, flow does not substantially influence vessel tone when MP-HbA is present. Thus, MP-HbA probably does enter the cell-free zone. These data suggest that as little as 5 μ M MP-HbA can reduce NO bioavailability upon transfusion of old blood, an amount that would be present after transfusion of just 1–2 U. [Supported by HL098032]. Disclosure Nothing to disclose.

In reply to “Transfusion of older blood and risk of death: unanswered questions”

In reply to “Transfusion of older blood and risk of death: unanswered questions”

Old blood bad? Either the biggest issue in transfusion medicine or a nonevent

Old blood bad? Either the biggest issue in transfusion medicine or a nonevent

Red blood cell storage lesion and adverse clinical outcomes: post hoc ergo propter hoc?

Red blood cell storage lesion and adverse clinical outcomes: post hoc ergo propter hoc?

The age of transfused blood predicts hematocrit response among critically ill surgical patients

BackgroundIn vitro data suggest that erythrocytes undergo storage time-dependent degradation, eventuating in hemolysis. We hypothesize that transfusion of old blood, as compared with newer blood, results in a smaller increment in hematocrit. MethodsWe performed an analysis of packed red blood cell transfusions administered in the surgical intensive care unit. Age of blood was analyzed as continuous, dichotomized at 14 days (old vs new), and grouped by weeks old. ResultsA total of 136 U of packed red blood cells were given to 52 patients; 110 (80.9%) were 14 days old or more. A linear, inverse correlation was observed between the age of blood and the increment in hematocrit (r2 = −.18, P = .04). The increment in hematocrit was greater after transfusion of new as compared with old blood (5.6% vs 3.5%, respectively; P = .005). A linear relationship also was observed between the age of transfused blood in weeks and the increment in hematocrit (P = .02). ConclusionsThere is an inverse relationship between the age of blood and the increment in hematocrit. The age of blood should be considered before transfusion of surgical patients with intensive care unit anemia.

The Association Between the Transfusion of Older Blood and Outcomes After Trauma

Allogeneic packed red blood cells (PRBCs) suppress immunity and influence outcomes. The influence of blood on the risk of infection and death may be related to the duration of storage. We sought to determine whether blood storage duration was associated with infection or death in a large cohort of injury victims. We reviewed a cohort of trauma patients transfused at least 1 U of PRBCs within 24 h of admission to a level 1 trauma center. The outcomes of interest were complicated sepsis and mortality. We compared the amount of older blood (>14 days storage) given to patients who did or did not develop the outcomes of interest using univariate and multivariate methods. A total of 820 patients were included. Patients who died (n = 117) received more units of older blood than those who lived (5 U [inter quartile range {IQR}, 2-9] vs. 3 U [IQR, 2-6]; P < 0.001). Patients with complicated sepsis (n = 244) received a greater volume of older blood than those without complicated sepsis (6 U [IQR, 2-10] vs. 3 U [IQR, 1-5]; P < 0.001). After adjusting for clinical factors, including the total amount of blood transfused, patients receiving greater than or equal to 7 U of older blood had a higher risk of complicated sepsis than patients receiving 1 or fewer units (odds ratio, 1.9; P = 0.03). The risk for complicated sepsis and death in trauma victims who are transfused blood is high. The amount of older blood transfused is associated with complicated sepsis. Although the best strategy to minimize the effects of allogeneic blood is to avoid unnecessary transfusions, it may be particularly important to avoid transfusing multiple units of older blood.

Prestorage Leukoreduction Ameliorates the Effects of Aging on Banked Blood

Previous studies have demonstrated that the transfusion of older blood is independently associated with higher rates of infectious complications, multiple organ failure, and mortality. Putative mechanisms implicate leukocytes in stored blood that generate immunomodulatory mediators as the stored blood ages. The purpose of this retrospective cohort study was to describe the effect of prestorage leukoreduction (PS-LR) on the detrimental clinical effects of increasing age on blood products used in trauma patients. All patients receiving >or=6 units of packed red cells and surviving >or=48 hours since May 1999 when institutional universal PS-LR was begun were identified. Transfusion requirements, demographic data, and causes of death were collected. Blood bank records were reviewed to determine the age of each unit of blood transfused. Multivariate logistic regression was used to determine the relationship between the age of PS-LR transfused blood and mortality after adjusting for total transfusion requirement, patient age, Injury Severity Score, head Abbreviated Injury Score, mechanism of injury, and gender. A subgroup analysis was performed excluding those patients in whom care was withdrawn at 48 hours to 72 hours postinjury for brain death or neurologic devastation. A total of 399 patients, receiving 6,603 units of blood, met inclusion criteria. Mortality analysis showed that increasing Injury Severity Score, patient age, head Abbreviated Injury Score, and number of units of packed red cells transfused were all independently associated with an increased risk of death. When mean age of blood was analyzed as a continuous variable, a significant reduction in the risk of death with increasing mean age of transfused PS-LR blood was noted (odds ratio [OR], 0.959; 95% confidence interval [CI], 0.924-0.996). Both of these findings persisted when the mean age of blood was dichotomized at 14 days (OR, 0.426; 95% CI, 0.182-0.998) and 21 days (OR, 0.439; 95% CI, 0.225-0.857). The area under the curve for the receiver operating characteristics of our mortality model was 0.90. After excluding 13 patients in whom care was withdrawn 48 hours to 72 hours postinjury for brain death or neurologic devastation, the mortality analysis still showed that increasing injury severity, number of units of packed red cells transfused, and age were all independently associated with an increased risk of death. The protective effect of receiving older blood seen in the all-cause mortality analysis disappeared because no association was found between odds of dying and increasing age of packed red blood cells units transfused. This was true whether the mean age of transfused blood was dichotomized at 14 days (OR, 0.93; CI, 0.30-2.83) or at 21 days (OR, 0.54; CI, 0.25-1.16). Our data suggest that the deleterious effects of aging on banked blood are ameliorated by PS-LR. We are currently conducting a prospective observational study in an effort to duplicate the findings of this retrospective investigation.

The red blood cell storage lesion: a method to the madness

The red blood cell storage lesion: a method to the madness

Transfusion of Aged Packed Red Blood Cells Results in Decreased Tissue Oxygenation in Critically Injured Trauma Patients

Blood transfusion is a common event in the treatment of injured patients. The effect of red blood cell transfusion on tissue oxygenation is unclear. The transfusion of older blood has been shown to be detrimental in retrospective studies. This study aims to study the effect of the age of the blood transfused on the tissue oxygenation using near infrared spectroscopy. Thirty-two critically injured trauma patients for whom a blood transfusion had been ordered were recruited. Each patient had a transcutaneous probe placed on the thenar eminence. The probe was placed 1 hour before the transfusion and left in place until 4 hours after transfusion. Tissue oxygen saturation (Sto2) was recorded every 2 minutes. The Sto2 area under the curve (AUC) over time periods was calculated. A control group (n = 16), not transfused, was recruited. The transfusion group was divided into two groups by blood age. One group received blood less than 21 days old, (new blood, n = 15) and the other received blood 21 days old or greater (old blood, n = 17). The data were analyzed for significance with Kendall's W and Wilcoxon's signed rank test (p < 0.05). Baseline characteristics such were not significantly different between groups. The baseline AUC did not differ between groups. The old blood group demonstrated a significant decline in Sto2 comparing its baseline period to its transfusion period (p < 0.05). There was no similar decline in the control group or the new blood group. The posttransfusion period AUC for the old blood group was also lower versus baseline (p = 0.06). There was a moderate correlation between increasing age of blood and decrease in oxygenation (r = 0.5). There was a decrease in peripheral tissue oxygenation in patients receiving older red blood cells. There was no oxygenation decrease in patients receiving blood less than 21 days. This indicates that factors in stored blood may influence the peripheral vasculature and oxygen delivery.

Increased rate of infection associated with transfusion of old blood after severe injury : P.J. Offner, E.E. Moore, W.L. Biffl, et al. Arch Surg 137:711–717, 2002

Increased rate of infection associated with transfusion of old blood after severe injury : P.J. Offner, E.E. Moore, W.L. Biffl, et al. Arch Surg 137:711–717, 2002

Increased rate of infection associated with transfusion of old blood after severe injuryP.J. Offner, E.E. Moore, W.L. Biffl, et al. Arch Surg 137:711–717, 2002

Increased rate of infection associated with transfusion of old blood after severe injuryP.J. Offner, E.E. Moore, W.L. Biffl, et al. Arch Surg 137:711–717, 2002

Increased rate of infection associated with transfusion of old blood after severe injury.

Blood components undergo changes during storage that may affect the recipient, including the release of bioactive agents, with significant immune consequences. We hypothesized that transfusion of old blood increases infection risk in severely injured patients. Prospective cohort study. Urban level I regional trauma center. Sixty-one trauma patients with an Injury Severity Score greater than 15, age older than 15 years, and survival longer than 48 hours who were transfused with 6 to 20 U of red blood cells in the first 12 hours after injury were studied. By means of blood bank records, the age of each unit of blood was determined. Transfusion of allogeneic red blood cells. Major infectious complications. The early (<12 hours) transfusion requirement was 12 +/- 0.6 U, with a mean age 27 +/- 1 days. Major infections developed in 32 patients (52%). Age and Injury Severity Score were not significantly different between patients who developed infections and those who did not (age, 39 +/- 4 vs 36 +/- 3 years; Injury Severity Score, 33 +/- 1.5 vs 29 +/- 1.5). Transfusion of older blood was associated with subsequent infection; patients who developed infections received 11.7 +/- 1.0 and 9.9 +/- 1.0 U of red blood cells older than 14 and 21 days, respectively, compared with 8.7 +/- 0.8 and 6.7 +/- 0.08 in patients who did not develop infections (both P<.05, t test). Multivariate analysis confirmed age of blood as an independent risk factor for major infections. Transfusion of old blood is associated with increased infection after major injury. Other options, such as leukocyte-depleted blood or blood substitutes, may be more appropriate in the early resuscitation of trauma patients requiring transfusion.

Prospective, randomized trial of the safety and efficacy of a limited donor exposure transfusion program for premature neonates

We investigated the safety and efficacy of using a single unit of packed red blood cells until its expiration date (35 days) to meet the transfusion needs of infants weighing <1.5 kg. Unit concentration of potassium and infants' hematocrit value, K + level, pH, and base excess were measured before and after transfusion. Compared with control infants, study infants had similar transfusion needs, but received blood from significantly fewer donors. The age of the blood received by study infants was significantly older and had a higher plasma K + level. However, the change in infants' serum K + levels before and after a transfusion was not significantly different in the two groups, and no adverse effects from transfusion of older blood were observed. We conclude that a protocol that allows use of an assigned unit of packed red blood cells preserved with citrate- phosphate-dextrose-adenine anticoagulant until its expiration date is safe, minimizes donor exposures, and meets the transfusion needs of low birth weight neonates. (J P EDIATR 1994;125:92-6)