Red blood cell use outside the operating theater: a prospective observational study with modeling of potential blood conservation during severe blood shortages

BACKGROUND: National guidance recommends planning for future blood shortages, but few studies have evaluated how reduced demand could be achieved acutely.
STUDY DESIGN AND METHODS: A trained observer collected data concerning red blood cell (RBC) transfusion events outside the operating theater during 68 hours of blood bank monitoring over 7 weeks. Data were gathered at the patients' bedside from clinical staff and charts. Transfusions were classified according to the presence of bleeding and medical specialty (medical, surgical, other). Hemoglobin (Hb) transfusion triggers, RBCs transfused, and posttransfusion Hb values were collected. Evidence-based scenarios were used to model the potential RBC savings that could be achieved if acute shortages occurred, incorporating ischemic heart disease as a potential decision modifier.
RESULTS: A total of 83 patients received 100 transfusion events, comprising 207 RBC units, during the sampling periods. The relative use of RBC units across specialties was as follows: medical, 74%; surgical, 22%; and other, 4%. For medical and surgical patients, respectively, 31 and 10% of all RBC units were transfused for anemia without evidence of bleeding, and 38 and 12% were transfused for non–life-threatening bleeding. Eight-five percent of all patients who received transfusions had stable vital signs before transfusion. Our model suggested that only 11% of RBCs would be conserved by cancellation of major surgery, whereas 23% to 47% of all RBCs could be conserved by controlling transfusions to medical patients.
CONCLUSION: In institutions with patterns of blood use similar to ours, control of transfusions to medical patients is the most effective response to acute blood shortages.     

IMMUNOHEMATOLOGY: Storage of murine red blood cells enhances alloantibody responses to an erythroid‐specific model antigen

BACKGROUND: Red blood cell (RBC) alloimmunization can be a serious complication of blood transfusion, but factors influencing the development of alloantibodies are only partially understood. Within FDA‐approved time limits, RBCs are generally transfused without regard to length of storage. However, recent studies have raised concerns that RBCs stored for more than 14 days have altered biologic properties that may affect medical outcomes. To test the hypothesis that storage time alters RBC immunogenicity, we utilized a murine model of RBC storage and alloimmunization. STUDY DESIGN AND METHODS: Blood from transgenic HOD donor mice, which express a model antigen (hen egg lysozyme [HEL]) specifically on RBCs, was filter leukoreduced and stored for 14 days under conditions similar to those used for human RBCs. Fresh or 14‐day‐stored RBCs were transfused into wild‐type recipients. The stability of the HOD antigen and posttransfusion RBC survival were analyzed by flow cytometry. RBC alloimmunization was monitored by measuring circulating anti‐HEL immunoglobulin levels. RESULTS: Transfusion of 14‐day‐stored, leukoreduced HOD RBCs resulted in 10‐ to 100‐fold higher levels of anti‐HEL alloantibodies as detected by enzyme‐linked immunosorbent assay than transfusion of freshly collected, leukoreduced RBCs. RBC expression of the HOD antigen was stable during storage. CONCLUSIONS: These findings demonstrate that HOD murine RBCs become more immunogenic with storage and generate the rationale for clinical trials to test if the same phenomenon is observed in humans. Length of storage of RBCs may represent a previously unappreciated variable in whether or not a transfusion recipient becomes alloimmunized.     

The production of red blood cell alloantibodies in mice transfused with blood from transgenic Fyb-expressing mice

BACKGROUND: A murine model would be useful to identify which immune mechanisms could be manipulated to treat or prevent red blood cell (RBC) alloimmunization in patients who become sensitized to multiple or widely expressed antigens. STUDY DESIGN AND METHODS: Transgenic mice (B6CBAF1/J-Tg-Fy(b)) expressing the human Fy(b) antigen of the Duffy (Fy) blood group were donors. Recipient B6CBA-F1 mice received four weekly intravenous (IV) transfusions: either 0.3 mL of washed buffy coat-depleted RBCs or 0.3 mL of RBCs with spleen cells. Titers of immunoglobulin M (IgM) and immunoglobulin G (IgG) were measured in recipient serum samples by flow cytometry with RBCs from donor mice as target cells. Recipient serum samples were also tested against human RBCs of various Fy phenotypes. Additionally, RBC survival studies were performed in alloimmunized mice utilizing biotin-labeled Fy(b) transgenic mouse RBCs. RESULTS: B6CBA-F1 mice receiving washed buffy coat-depleted RBCs first made IgM, followed by IgG alloantibodies to transgenic mouse Fy(b)-positive RBCs. Recipients of Fy(b)-positive RBCs mixed with spleen cells also produced IgM and IgG alloantibodies, but at a slower rate than recipients of washed buffy coat-depleted RBCs. Serum samples showed specificity for Fy3, Fy(b), and Fy6. Decreased survival of transfused RBCs was evident at 24 hours after transfusion. CONCLUSIONS: It is possible to elicit the formation of anti-Fy alloantibodies by IV transfusion in mice that lack Fy antigens. The transfusion of RBCs alone was adequate to stimulate alloantibody production in B6CBA-F1 recipient mice. The survival of transfused Fy(b)-positive RBCs is diminished in sensitized mice. This model will be useful in further studies of RBC alloimmunization.     

Reduced deformability of stored red blood cells is associated with generation of extracellular vesicles

Throughout storage, red blood cells (RBCs) undergo detrimental changes in viability and their ability to effectively transport oxygen. RBC storage lesions are mediated, in part, by a progressive loss of cell deformability, and associated with the release of extracellular vesicles (EVs). Accumulation of EVs during the storage of RBCs correlates with a decrease in RBC surface area to volume ratio. Similarly, the loss of RBC-deformability is associated with loss of RBC surface area to volume ratio. In this study we thus tested whether loss of RBC-deformability is associated with increased RBC-EV production during blood storage.EVs obtained by differential centrifugation of stored RBCs (non-leukoreduced non-irradiated or leukoreduced γ-irradiated RBCs stored 35 or 28 days respectively) were enumerated by high-sensitivity flow cytometry. RBC deformability was quantified, using a cell-flow-properties-analyzer, by measuring the median cell elongation ratio (MER) and percentage of low and high deformable cells in the population (%, LDFC, and HDFC, respectively).The number of EVs was inversely correlated with the MER and positively correlated with the %LDFC with both measures showing highly significant logarithmic dependence with EV levels in stored RBCs. Considering how highly deformable cells did not correlate with EV formation as compared with low deformable RBCs we propose that the formation of EVs is a key factor leading to increased RBC-rigidity.     

Progress in modulating the RBC membrane to produce transfusable universal/stealth donor RBCs

Two approaches have been used to produce red blood cells (RBCs) that could be transfused, regardless of the ABO group of the donor and recipient, the so-called “universal donor” RBCs. The first approach has involved converting group A and B RBCs to group O by cleaving off the terminal immunodominant sugars; the second approach involves masking the A and B antigens with polyethylene glycol (PEG). The latter approach has also been used to mask all other blood group antigens on the RBC membrane, yielding so-called “stealth RBCs”; the hope is that such PEGylated RBCs (PEG-RBCs) will not react with any blood group antibodies and may not be recognized as foreign, thus not initiating an immune response. The former approach is well advanced. Clinical trials have shown that units of group B blood converted to group O, using a galactosidase, survived normally without any ill effects to recipients. Work is progressing on the efficient conversion of group A RBCs to group O. PEG-RBCs can be prepared that will not react with any blood group antibodies in vitro, but RBC survival in animals has not been good. Recent data show that PEG is immunogenic and can induce antibodies that shorten survival of transfused PEG-RBCs in rabbits.     

Insufficient nitric oxide bioavailability: a hypothesis to explain adverse effects of red blood cell transfusion

While transfusion of red blood cells (RBCs) is effective at preventing morbidity and mortality in anemic patients, studies have indicated that some RBC components have functional defects ("RBC storage lesions") that may actually cause adverse events when transfused. For example, in some studies patients transfused with RBCs stored more than 14 days have had statistically worse outcomes than those receiving "fresher" RBC units. Recipient-specific factors may also contribute to the occurrence of these adverse events. Unfortunately, these events have been difficult to investigate because up to now they have existed primarily as "statistical occurrences" of increased morbidity and mortality in large data sets. There are currently no clinical or laboratory methods to detect or study them in individual transfusion recipients. We propose a unifying hypothesis, centered on insufficient nitric oxide bioavailability (INOBA), to explain the increased morbidity and mortality observed in some patients after RBC transfusion. In this model, variables associated with RBC units (storage time; 2,3-diphosphoglycerate acid concentration) and transfusion recipients (endothelial dysfunction) collectively lead to changes in nitric oxide (NO) levels in vascular beds. Under certain circumstances, these variables are "aligned" such that NO concentrations are markedly reduced, leading to vasoconstriction, decreased local blood flow, and insufficient O(2) delivery to end organs. Under these circumstances, the likelihood of morbidity and mortality escalates. If the key tenets of the INOBA hypothesis are confirmed, it may lead to improved transfusion methods including altered RBC storage and/or processing conditions, novel transfusion recipient screening methods, and improved RBC-recipient matching.     

Emergency Supply Policy of Cryopreserved RBC and PLT: The Czech Republic Concept

Supply of blood for urgent substitution is a strategic logistical problem for the military medical services across the world. The limited shelf life of blood- derived bioproductsin the liquid state and the need for special transport and use conditions, apart from donor and donations availability are among the causes for concern. To solve these problems many national health-care authorities implemented the national emergency blood crisis policy, to get a large amount of blood at any time at any place in the case of disaster, terrorist attack or war. The civil therapeutic problems in immunohematolgy cases can also be solved by stocks of fresh and cryopreserved homologous or autologous blood for patients with rare RBCs antigens or HLA / HPA platelet refractoriness with no chance to use common blood. The short shelf life of fresh platelets limits their efficient inventory management and availability during a massive transfusion protocol. Building an inventory of frozen blood components can mitigate the risk of insufficient availability. Since the beginning of the century in the Czech Republic, used, like other countries, the use of of cryopreserved blood-derived bioproducts has become the current method used to overcome the shortages of a timely supply. The Military University Hospital, Prague, and its bank of cryopreserved blood have been operating under this policy since 2006. There is currently a stock of frozen RBCs for military reserve, for a national blood crisis and, also, a stock of rare RBC units. For crisis management there are also stored, frozen PLTs, which are used in the treatment of heavily bleeding polytrauma patients. Both the containment and research development mitigation policy programs are in place for civil / military emergency situations. Even pathogen reduced frozen PLTs and frozen RBCs were successfully investigated for clinical use if demands arose. Currently, it is possible to meet operational demand while reducing the number of resupply transports and loss of products due to expiration. A lesson has been learned from the current containment, reseach and mitigation programs of efficient blood supply management with cryopreserved blood and blood derived bioproducts.     

Comparative assessment of normal and methoxypolyethylene glycol-modified murine red cells on swimming endurance and hippocampal injury in hypoxic mice

BACKGROUND: Membrane grafting of methoxypolyethylene glycol (mPEG) provides a unique strategy in preventing the immunologic recognition in blood transfusion. mPEG‐modified red blood cells (mPEG‐RBCs) have acceptable in vitro properties and provide a useful solution to problems with clinical blood matching. The aim of this study was to demonstrate the physiologic normality of mPEG‐RBCs in mice. STUDY DESIGN AND METHODS: Mouse RBCs were withdrawn via cardiac bleed and modified with 1.0 mmol per L mPEG with succinimidyl propionate linker. The fluorescein‐labeled mPEG‐RBCs were then transfused into recipient mice for in vivo survival analysis. At the same time, the exsanguine mouse model was produced, and mice were transfused with mPEG‐RBCs. The effects of mPEG‐RBC transfusion on the hemoglobin (Hb) level, swimming endurance capacity, and hypoxic‐ischemic injury in hippocampal pyramidal cells of exsanguine mice were investigated. RESULTS: mPEG‐RBCs showed the same in vivo survival curve and t_½ as those of untreated RBCs. Transfusion of mPEG‐RBCs could elevate Hb level of exsanguine mice and improve their swimming endurance capacity, and histologic studies showed that mPEG‐RBCs could also restore the hypoxic‐ischemic injury of hippocampal pyramidal cells in exsanguine mice, which were similar with control RBCs. That is, mPEG‐RBCs functioned in a similar fashion to untreated RBCs in exsanguine mice. Therefore, these results revealed that mPEG‐RBCs had normal oxygen‐carrying capacity. CONCLUSION: In conclusion, the results confirmed that mPEG‐RBCs could perform their in vivo function of carrying O₂ and improve some physiologic indexes of exsanguine mice, and the physiologic normality of mPEG‐RBCs provides new findings for clinical use.     

In vitro clinical-grade generation of red blood cells from human umbilical cord blood CD34+ cells

BACKGROUND: There is no appropriate alternative source of red blood cells (RBCs) to relieve the worsening shortage of blood available for transfusion. Therefore, in vitro generation of clinically available RBCs from hematopoietic stem cells could be a promising new source to supplement the blood supply. However, there have been few studies about the generation of clinical‐grade RBCs by coculture on human mesenchymal stem cells (MSCs) and various cytokine supplements, even though the production of pure RBCs requires coculture on stromal cells and proper cytokine supplements. STUDY DESIGN AND METHODS: Umbilical cord blood (CB) CD34+ cells were cultured in serum‐free medium supplemented with two cytokine sets of stem cell factor (SCF) plus interleukin‐3 (IL‐3) plus erythropoietin (EPO) and SCF plus IL‐3 plus EPO plus thrombopoietin (TPO) plus Flt‐3 for 1 week, followed by coculture upon MSCs derived from bone marrow (BM) or CB for 2 weeks. RESULTS: Almost pure clinical‐grade RBCs could be generated by coculturing with CB‐MSCs but not BM‐MSCs. Expansion fold and enucleation rate were significantly higher in coculture with CB‐MSCs than BM‐MSCs. Despite a 2.5‐fold expansion of erythroblasts in the presence of TPO and Flt‐3 for 8 days, the final RBC count was higher without TPO and Flt‐3. CONCLUSIONS: This study is the first report on generating clinical‐grade RBCs by in vitro culture with human MSCs and compared effectiveness of several cytokines for RBC production. This provides a useful basis for future production of clinically available RBCs and a model of erythropoiesis that is analogous to the in vivo system.     

Anemia and blood transfusion in the critically ill patient: role of erythropoietin

Critically ill patients receive an extraordinarily large number of blood transfusions. Between 40% and 50% of all patients admitted to intensive care units receive at least 1 red blood cell (RBC) unit during their stay, and the average is close to 5 RBC units. RBC transfusion is not risk free. There is little evidence that 'routine' transfusion of stored allogeneic RBCs is beneficial to critically ill patients. The efficacy of perioperative recombinant human erythropoietin (rHuEPO) has been demonstrated in a variety of elective surgical settings. Similarly, in critically ill patients with multiple organ failure, rHuEPO therapy will also stimulate erythropoiesis. In a randomized, placebo-controlled trial, therapy with rHuEPO resulted in a significant reduction in RBC transfusions. Despite receiving fewer RBC transfusions, patients in the rHuEPO group had a significantly greater increase in hematocrit. Strategies to increase the production of RBCs are complementary to other approaches to reduce blood loss in the intensive care unit, and they decrease the transfusion threshold in the management of all critically ill patients.     

Application of a computer program to exclude additional unexpected antibodies

BACKGROUND : When a patient has produced red cell (RBC) antibodies in the past, he or she is at risk of producing additional antibodies after antigen challenge. The presence of these antibodies should be excluded before each transfusion. The following criteria are applied when using commercial test RBCs: RBCs should not express the antigen against which the previously documented antibody is directed. For other clinically significant antigens, at least one RBC sample should be from a donor who is homozygous for the encoding gene. The manual selection of such RBCs is tedious and requires experience. STUDY DESIGN AND METHODS : A computer program has been developed that generates exclusion panels (EPs) by selecting a minimum number of RBCs from commercial test panels complying with current criteria. When RBCs from a donor who is homozygous for the encoding gene are absent, the program selects, as a second-best option, RBCs from a donor who is heterozygous for that gene. The computer program developed for this study investigated the usefulness of commercially available panels from separate manufacturers in excluding the presence of additional antibodies. A list of 488 antibodies detected by a regional blood bank in 1994 was used as cases of antibodies documented in the past. RESULTS : In 61 percent of the cases, successful EPs (i.e., those complying with the criteria), consisting of three to four different phenotypes, were selected. In the remaining 39 percent of cases, it was impossible to generate successful EPs: 1 to 2 additional antibodies could not be excluded or could be excluded only by using RBCs from heterozygotes. Commercial panels differed only slightly in their efficiency in providing suitable RBCs. None of the commercial panels could provide suitable RBCs to exclude all additional antibodies in the presence of anti-c, anti-e, or anti-M. Increasing the number of RBCs from which to select EPs only slightly increased the percentage of success. CONCLUSION : Computer-aided construction of EPs quickly shows whether strict criteria can be met or whether alternative techniques should be used. It leads to a significant reduction in the number of RBC suspensions necessary to exclude additional antibodies. Results with various commercial panels differed only slightly.     

Recipient inflammation affects the frequency and magnitude of immunization to transfused red blood cells

BACKGROUND: Most alloantigens on transfused red blood cells (RBCs) are weakly immunogenic, with only a 2 to 6 percent overall immunization rate even in patients receiving multiple transfusions. Although recipient genetics may contribute to responder and/or nonresponder status, in most cases HLA type does not predict humoral response to RBC antigens. In contrast, rates of alloimmunization do correspond to the underlying disease status of transfusion recipients, suggesting that acquired host factors may play an important role. In this context, it was hypothesized that the inflammatory status of a transfusion recipient would influence immunization to transfused RBCs. STUDY DESIGN AND METHODS: A novel murine model for alloimmunization to RBC antigens was developed with the mHEL mouse, which expresses hen egg lysozyme (HEL) as a model blood group antigen. Leukoreduced mHEL RBCs were transfused into wild-type recipient mice, and anti-HEL responses were monitored. To test the stated hypothesis, some recipient animals were injected with polyinosinic polycytidylic acid (poly(I:C)), a synthetic double-stranded RNA molecule that induces viral-like inflammation. RESULTS: Similar to the immunogenicity of most RBC antigens in humans, transfusion of mHEL RBCs into uninflamed mice was only a weak immunogen. In contrast, poly(I:C)-treated mice had a significant increase in both the frequency and the magnitude of alloimmunization to the mHEL antigen. CONCLUSIONS: These findings demonstrate that recipient inflammation with poly(I:C) significantly enhances humoral immunization to transfused alloantigens in a murine model. Moreover, these data suggest that the inflammatory status of human transfusion recipients may regulate the immunogenicity of transfused RBCs.     

Modeling red cell procurement with both double-red-cell and whole-blood collection and the impact of European travel deferral on units available for transfusion

BACKGROUND: In 1997 the FDA approved the first double-red-blood-cell (2RBC) collection device. Soon after, travel deferral for variant Creutzfeldt-Jakob disease (vCJD) risk was adopted. To show the importance of including 2RBCs in predictive models of the blood supply, an existing whole-blood (WB) model was updated to include 2RBC collection and then run to simulate the effect of vCJD deferral on total RBC availability. STUDY DESIGN AND METHODS: The model simulates donation of allogeneic WB and 2RBCs, with donors stratified into eight age and sex groups. The model was updated with 2003 donation and economic data from 16 blood centers. RESULTS: The distribution of donations by demographic group differed both within and between WB and 2RBCs. Overall, 2RBC donation made up 24 percent of transfusable RBC units, at a lower per-unit acquisition cost from both the blood bank and the societal perspectives. Component fees from hospitals would alter this interpretation. The model predicts that vCJD travel deferral led to a 3.3 percent (95% confidence interval [CI], 2.3-4.1) decrease in the total number of RBC units, which was more than offset by 2RBC collection, resulting in a 10.4 percent (95% CI, 9.8%-11.1%) net increase in RBC units. Modeled 2RBC results match operational records, whereas vCJD deferral is overestimated. CONCLUSION: Shifting to 2RBC collection led to a substantial gain in available RBCs: even with policies that adversely affect the quantity of RBCs in the supply, 2RBC collection results in a net gain. The economics of 2RBC collection are not as clear, however.     

Investigation of red cell size distribution histograms of normal male and female subjects

Size distribution histograms characterizing the red blood cell (RBC) populations of normal subjects are provided. Separate haemocytometric reference ranges were established for apparently healthy male and female adults by using an Ortho ELT 800 Hematology Analyzer, which is based on the principle of measuring light scattering intensity (LSI). Effects of sphering RBCs on some characteristics of size distribution histograms were also investigated. The absolute distribution width at half peak height (ADW0.5) of RBC size distribution histograms of sphered RBCs is shown to be approximately 40% lower than for unsphered RBCs. The mean RBC size distribution histogram determined for the group of female subjects was shown to be significantly shifted to the right in comparison with the mean size distribution histogram calculated for males, indicating a sex-related difference. The shift is concordant with a significantly higher fraction of microcytes in male subjects, as well as with lower mean corpuscular volume (MCV) values in males compared with females.     

The role of erythropoietin therapy in the critically ill

Critically ill patients receive an extraordinarily large number of blood transfusions. Between 40% and 50% of all patients admitted to intensive care units (ICUs) receive at least one allogeneic red blood cell (RBC) unit and average close to 5 U of RBCs during their ICU admission. RBC transfusion is not risk-free, and there is little evidence that "routine" transfusion of stored allogeneic RBCs is beneficial to critically ill patients. It is clear that most critically ill patients can tolerate hemoglobin levels as low as 7 g/dL, and therefore, a more conservative approach to RBC transfusion is warranted. Anemia of critical illness is a distinct clinical entity characterized by blunted erythropoietin (EPO) production and abnormalities in iron metabolism identical to what is commonly referred to as anemia of chronic disease. As such, the bone marrow in many of these patients responds to the administration of exogenous EPO, in spite of their underlying critical illness. The efficacy of perioperative recombinant human erythropoietin (rHuEPO) has been demonstrated in a variety of elective surgical settings. Similarly, in critically ill patients, rHuEPO therapy will also stimulate erythropoiesis. In randomized placebo-controlled trials, therapy with rHuEPO resulted in a significant reduction in allogeneic RBC transfusions. Strategies to increase the production of RBCs are complementary to other approaches to reduce blood loss in the ICU and decrease the transfusion threshold in the management of all critically ill patients.     

Transfusion to blood group A and O patients of group B RBCs that have been enzymatically converted to group O

BACKGROUND: The transfusion of ABO-incompatible RBCs is the leading cause of fatal transfusion reactions. Group O RBCs, lacking terminal immunodominant A and B sugars to which humans are immunized, are safe for transfusion to persons of any ABO blood group. With the use of a recombinant alpha-galactosidase to remove terminal galactose from group B RBCs, the safety and efficacy of enzyme-converted group-B-to-group-O (ECO) RBC components were studied in transfusion-dependent patients. STUDY DESIGN AND METHODS: Twenty-four patients (blood groups A and O) were randomly assigned to receive transfusion(s) of either ECO or control group O RBCs. If a second transfusion was given, the other blood component was administered. RESULTS: Twenty-one patients were given ECO RBCs; 18 also underwent control transfusions. One patient received only a small aliquot for RBC survival studies, instead of a full-unit transfusion, because his serum was incompatible with ECO RBCs. No adverse events occurred. Both ECO and control transfusions resulted in appropriate Hb increments and comparable (51)Cr-labeled RBC survival studies. One patient developed a transient, weak-positive DAT, without hemolysis. Two weeks after transfusion, 5 of 19 evaluable ECO RBC recipients had increases in anti-B titers. CONCLUSION: ECO RBCs were comparable to group O cells for safety and efficacy in this study. The clinical significance of the increase in anti-B and of occasional serologic incompatibilities with ECO RBCs is unclear. If strategies can be developed to remove A epitopes, enzymatic conversion could be used to create a universal (group O) donor blood supply.     

Preoperative red cell production in patients undergoing weekly autologous blood donation

BACKGROUND: Modest autologous blood donation programs involving weekly phlebotomy and threshold hematocrits for blood donation higher than 33 percent are frequently used in patients scheduled for elective cardiac surgery. This study was performed to determine the gain in red cells (RBCs) obtained with such a program. STUDY DESIGN AND METHODS: The blood bank and medical records of 225 adult patients (194 men, 31 women; mean age, 57 years [range, 18–77]) who donated blood for autologous use in elective cardiac surgery during a 3-year period were reviewed. Preoperative RBC production was estimated by the total volume of RBCs donated minus the change in circulating RBC volume between the first donation and the day before surgery. RESULTS: A total of 604 blood units were donated (2.7 units/patient; range, 1–3). The mean volume of RBCs donated was 522 mL (range, 171–732). Mean RBC production (over baseline RBC production) was 351 mL (range, 9–719), or 19 percent (range, 0.5-40) of the circulating RBC volume at baseline. CONCLUSION: A modest autologous blood donation program using three phlebotomies at weekly intervals and a threshold hematocrit for blood donation of 36 percent yields an average of 351 mL (range, 9–719) of RBCs. This is equivalent to 2 units (range, 0.5-4) of allogeneic packed RBCs at 180 mL per unit.     

Innate Immune Activation After Transfusion of Stored Red Blood Cells

The transfusion of red blood cells (RBCs), although necessary for treatment of anemia and blood loss, has also been linked to increased morbidity and mortality. RBCs stored for longer durations and transfused in larger volumes are often cited as contributory to adverse outcomes. The potential mechanisms underlying deleterious effects of RBC transfusion are just beginning to be elucidated. In this narrative review, we explore the hypothesis that prolonged RBC storage results in elaboration of substances which may function as danger associated molecular pattern molecules that activate the innate immune system with consequences unfavorable to healthy homeostasis. The nature of these chemical mediators and the biological responses to them offers insight into the mechanisms of these pathological responses. Three major areas of activation of the innate immune apparatus by stored RBCs have been tentatively identified: RBC hemolysis, recipient neutrophil priming, and reactive oxygen species production. The possible mechanisms by which each might perturb the innate immune response are reviewed in a search for potential novel pathways through which transfusion can lead to an altered inflammatory response.     

Coexistence of autoantibodies and alloantibodies to red blood cells due to blood transfusion

BACKGROUND: Autoantibodies (AUTO) to red blood cells (RBCs) are frequently associated with alloantibodies (ALLO). The mechanism for the coexistence of these antibodies is obscure. STUDY DESIGN AND METHODS: Between August 1998 and June 2006, all in- and outpatients of the Charité University Hospital, Berlin, with detectable AUTO were included in this study. Serologic examination was performed with standard techniques for the detection of RBC antibodies. RESULTS: A total of 717 patients were found to have AUTO, with ALLO observed in 200 of these patients (28%). The history of antibody production could be evaluated in 98 of the 200 patients. Both AUTO and ALLO were due to RBC transfusion in 73 cases (75%) and peripheral blood progenitor cell transplantation in 6 cases (6%). Nine (9%) patients were primarily alloimmunized and subsequently developed AUTO. The remaining 10 (10%) patients were primarily autoimmunized and later developed ALLO. Only 6 of these patients had chronic idiopathic autoimmune hemolytic anemia. CONCLUSION: The majority of AUTO associated with ALLO appears to be due to RBC transfusion that must be recognized as a major cause for autoimmunization.     

Effect of inositol hexaphosphate–loaded red blood cells (RBCs) on the rheology of sickle RBCs

BACKGROUND: The recent in vitro demonstration that inositol hexaphosphate–loaded red blood cells (IHP‐RBCs) may reduce the risks of sickling of sickle RBCs (SS RBCs) exposed to hypoxia make these modified RBCs potentially useful in transfused sickle cell anemia (SCA) patients. STUDY DESIGN AND METHODS: Hemorheologic properties of IHP‐RBCs, normal RBCs (AA RBCs), SS RBCs, SS RBCs plus AA RBCs, and SS RBCs plus IHP‐RBCs were compared under normoxia and/or after hypoxic challenges. RESULTS: Although IHP‐RBCs have reduced deformability compared with SS RBCs or AA RBCs, IHP‐RBCs exhibited lower aggregability than AA RBCs and SS RBCs and, when mixed with SS RBCs, the aggregation level was below the one of SS RBCs alone or SS RBCs plus AA RBCs. Blood viscosity of SS RBC plus IHP‐RBC suspension was lower than the viscosity of SS RBCs alone and greater than viscosity of SS RBCs plus AA RBCs. The hypoxic challenge was detrimental for deformability and viscosity of SS RBCs alone or SS plus AA RBC suspension but not for SS plus IHP‐RBC suspension. CONCLUSION: Our results support the fact that IHP‐RBCs could be useful in SCA by decreasing RBC aggregation and blunting the adverse effects of hypoxia on RBC deformability and blood viscosity.