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.     

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.     

Blood management in intensive care medicine: CRIT and ABC – what can we learn?

In 284 US intensive care units the CRIT study (Anemia and blood transfusion in the critically ill – Current clinical practice in the United States) assessed allogeneic red blood cell (RBC) transfusion and outcome in 4892 patients. As in the former European ABC study (Anemia and blood transfusion in the critically ill), the mean pretransfusion hemoglobin was approximately 8.5 g/dl and RBC transfusions were independently associated with an increased mortality. These studies were purely observational and, therefore, despite the finest statistical models indicating that RBC transfusions were independently associated with a higher mortality, it remains possible that this adverse outcome is not due to a harmful effect of RBC transfusion in itself, but merely reflects the fact that transfused patients were sicker to start with. The definitive call is still out, but one mechanism by which RBC transfusion might be harmful now appears less likely; namely, storage lesion. In the CRIT study, mortality was not increased in patients receiving 'old' RBCs (>14 days stored) versus 'fresh' RBCs. The effect of leukoreduction could not be assessed since mainly nonleukoreduced RBCs were transfused. The evidence is mounting, however, that RBC transfusions are efficacious only when oxygen delivery is compromised. What can be done to diminish the use of RBC transfusions, its costs and side effects in intensive care medicine? There are two important options available today: decreasing blood loss for diagnostic purposes using pediatric sampling tubes, and establishing restrictive multidisciplinary transfusion guidelines and implementing them in daily clinical practice.     

Clinical consequences of red cell storage in the critically ill

Red cell (RBC) transfusions are a potentially life-saving therapy employed during the care of many critically ill patients to replace losses in hemoglobin to maintain oxygen delivery to vital organs. During storage, RBCs undergo a series of biochemical and biomechanical changes that reduce their survival and function. Additionally, accumulation of other biologic by-products of RBC preservation may be detrimental to recipients of blood transfusions. Laboratory studies and an increasing number of observational studies have raised the possibility that prolonged RBC storage adversely affects clinical outcomes. In this article, the laboratory and animal experiments evaluating changes to RBCs during prolonged storage are reviewed. Subsequently, the clinical studies that have evaluated the clinical consequences of prolonged RBC storage are reviewed. These data suggest a possible detrimental clinical effect associated with the transfusion of stored RBCs; randomized clinical trials further evaluating the clinical consequences of transfusing older stored RBCs are required.     

Blood management in intensive care medicine: CRIT and ABC--what can we learn?

In 284 US intensive care units the CRIT study (Anemia and blood transfusion in the critically ill--Current clinical practice in the United States) assessed allogeneic red blood cell (RBC) transfusion and outcome in 4892 patients. As in the former European ABC study (Anemia and blood transfusion in the critically ill), the mean pretransfusion hemoglobin was approximately 8.5 g/dl and RBC transfusions were independently associated with an increased mortality. These studies were purely observational and, therefore, despite the finest statistical models indicating that RBC transfusions were independently associated with a higher mortality, it remains possible that this adverse outcome is not due to a harmful effect of RBC transfusion in itself, but merely reflects the fact that transfused patients were sicker to start with. The definitive call is still out, but one mechanism by which RBC transfusion might be harmful now appears less likely; namely, storage lesion. In the CRIT study, mortality was not increased in patients receiving 'old' RBCs (>14 days stored) versus 'fresh' RBCs. The effect of leukoreduction could not be assessed since mainly nonleukoreduced RBCs were transfused. The evidence is mounting, however, that RBC transfusions are efficacious only when oxygen delivery is compromised. What can be done to diminish the use of RBC transfusions, its costs and side effects in intensive care medicine? There are two important options available today: decreasing blood loss for diagnostic purposes using pediatric sampling tubes, and establishing restrictive multidisciplinary transfusion guidelines and implementing them in daily clinical practice.     

The Age of Blood Evaluation (ABLE) randomized controlled trial: study design

Red blood cells (RBCs) are transfused to treat anemia and to maintain oxygen delivery to vital organs during critical illness. Laboratory and observational studies have raised the possibility that prolonged RBC storage may adversely affect clinical outcomes. Compared with RBCs stored less than 1 week, there are no clinical data demonstrating that RBCs stored longer remain as effective at carrying or releasing oxygen, and observational studies have risen to possibility that prolonged RBC storage might result in harm to vulnerable patients requiring blood transfusions. The "Age of Blood Evaluation" (ABLE) study (ISRCTN44878718) is a double-blind, multicenter, parallel randomized controlled clinical trial. It will test the hypothesis that the transfusion of prestorage leukoreduced RBCs stored for 7 days or less (fresh arm) as compared with standard-issue RBCs stored, on average, 15 to 20 days (control arm) will lead to lower 90-day all-cause mortality and reduced morbidity in critically ill adults. We include adults in intensive care units (ICUs) who (1) have had a request for a first RBC unit transfusion during the first 7 days of ICU admission and (2) have an anticipated requirement for ongoing invasive and noninvasive mechanical ventilation exceeding 48 hours. Enrolled patients are randomized at the time of transfusion to receive either standard-issue RBC units or RBCs stored 7 days or less issued by the local hospital transfusion service. The primary outcome is 90-day all-cause mortality. Secondary outcomes include ICU and hospital mortality, organ failure, and serious nosocomial infections. With 2510 patients, we will be able to detect a 5% absolute risk reduction (from 25% to 20%). The ABLE study is currently enrolling patients in 23 university-affiliated and community-hospital ICUs across Canada; sites in France and United Kingdom are expected to start recruitment in 2011. Regardless of the results, ABLE study will have significant implications on the duration of RBC storage. A negative trial will reassure clinicians and blood bankers regarding the effectiveness and safety of standard-issue RBCs. A positive trial will have significant implications with respect to inventory management of RBCs given to critically ill adults with a high risk of mortality and will also prompt research to better understand the RBC storage lesion in the hopes of minimizing its clinical consequences through the development of better storage methods.     

2008 Emily Cooley Memorial Lecture: lessons learned from pediatric transfusion medicine clinical trials . . . a little child shall lead them

BACKGROUND: Many clinical practices in transfusion medicine are controversial and/or lack definitive guidelines established by sound clinical trials. Although recommendations based on results of clinical trials performed using infants and children may not always be applied directly to adults—and vice versa—lessons learned from pediatric trials can be useful when critically assessing the design/results/conclusions of adult trials.
STUDY DESIGN AND METHODS: Four randomized clinical trials (RCTs) studying pediatric patients were critically reviewed. They addressed two red blood cell (RBC) transfusion issues: 1) transfusion guidelines by which RBC transfusions are "triggered" by liberal (LIB; high pretransfusion patient hematocrit [Hct] levels) versus being "triggered" by restricted (RES; low pretransfusion Hct levels) and 2) transfusion of fresh RBCs (≤7 days' storage) versus RBCs (up to 42 days' storage).
RESULTS: Findings established by primary outcomes generally were firm (e.g., fewer RBC transfusions were given to infants/children managed by RES guidelines; transfusing small volumes of RBCs stored up to 42 days to preterm infants diminished allogeneic donor exposures and were equally efficacious and safe as fresh RBCs stored ≤7 days). Findings based on secondary outcomes, subset, and post hoc analyses were inconsistent (e.g., clinical outcomes were equivalent after LIB or RES transfusions in only two of three RCTs; in the third, more neurologic problems were found in neonates given RES transfusions).
CONCLUSIONS: Clinical practices should be based on data pertaining to the primary outcomes of RCTs, because trials are designed and statistically powered to address these issues. Clinical practices suggested by analysis of secondary outcomes, subsets of patients, and post hoc analyses should be applied cautiously until studied further—ideally, as primary outcomes in subsequent RCTs.     

Harmful effects of transfusion of older stored red blood cells: iron and inflammation

Retrospective studies suggest that the transfusion of older, stored red blood cells (RBCs) may be associated with increases in mortality, serious infections, multiorgan failure, thrombosis, and hospital length of stay. Our research is based on the overarching hypothesis that the adverse effects associated with transfusion of older, stored RBCs result from the acute delivery of hemoglobin iron to the monocyte-macrophage system. To test this "iron hypothesis," we are recruiting healthy human volunteers to donate double, leukoreduced, RBC units. We then transfuse them with one autologous fresh unit (i.e., after 3-7 days of storage) and one older, stored unit (i.e., at 40-42 days of storage). The primary study outcome will compare laboratory iron measures and proinflammatory cytokines after transfusion of fresh or older, stored RBCs. Similar studies using allogeneic RBC transfusions will be performed in chronically transfused patients with either sickle cell disease or β-thalassemia. Although prospective, randomized studies will ultimately determine the existence of adverse effects from transfusing older, stored RBCs, our goal is to determine the mechanism(s) for this potential effect.     

Transfusion of stored red blood cells adhere in the rat microvasculature

BACKGROUND: Ex vivo storage of red blood cells (RBCS) for transfusions is associated with a “storage lesion,” which decreases RBC deformability and increases RBC adhesiveness to vascular endothelium. This may impair microcirculatory flow with deleterious effects on oxygen delivery after transfusion. Previous studies have shown that human RBCs adhere to endothelial monolayers in vitro with prolonged storage and is reduced by prestorage leukoreduction (LR). The objective of this study was to determine whether duration of RBC storage and LR influence RBC adhesion in vivo in capillaries. STUDY DESIGN AND METHODS: Rat RBCs were collected and stored in CPDA‐1 under standard blood bank conditions. Three RBC products were compared: 1) fresh RBCs, less than 24 hours of storage (n = 6); 2) nonleukoreduced (NLR) RBCs stored for 7 days (n = 6); and 3) prestorage LR RBCs stored for 7 days (n = 6). RBCs were labeled with fluorescein isothiocyanate (FITC) 24 hours before transfusion and reinjected in an isovolemic manner into healthy rats. The FITC‐labeled RBCs were visualized in the extensor digitorum longus muscle using intravital video microscopy (20× magnification). The number of RBCs adherent in capillaries was counted 1 hour after transfusion in 10 random fields and the median values were compared with one‐way analysis of variance. RESULTS: Stored RBCs showed increased levels of adherence in capillaries compared to their fresh counterparts (p < 0.05). Prestorage LR decreased RBC adherence to levels equivalent to those of fresh RBCs (p < 0.05 for stored LR vs. stored NLR). CONCLUSION: Rat RBCs stored under conditions that closely mimicked clinical transfusion adhere in capillaries. The decreased RBC adherence with LR suggest a direct effect of white blood cells or their byproducts on RBC deformability and/or adhesiveness to microvascular endothelium. Further study will examine the mechanism of adherence and the impact it has on microcirculatory flow and oxygen delivery in the critically ill host.     

Controversies in the management of the anemia of prematurity using single-donor red blood cell transfusions and/or recombinant human erythropoietin

Many controversial questions regarding the practice of neonatal red blood cell (RBC) transfusions exist, so that practices and policies vary widely. This article will critically assess information pertaining to two of these controversies, namely, the transfusion of RBCs stored for up to 42 days after collection vs the transfusion of fresh RBCs stored 7 days or less after donation and the use of recombinant human erythropoietin (rHuEPO) in attempts to either diminish the severity of or to treat the anemia of prematurity. Based on both theoretical considerations and several published clinical trials, RBCs from one donor stored up to 42 days in extended storage preservative solutions can safely provide all RBCs needed by most infants for small-volume transfusions. Based on a large number of clinical trials and a meta-analysis of these trials, it is impossible to provide firm guidelines for the use of rHuEPO in the treatment of the anemia of prematurity. Clearly, rHuEPO has efficacy in stimulating erythropoiesis in preterm infants, but success in the elimination or marked reduction in the need for RBC transfusions has not been definitively demonstrated.     

Debate: transfusing to normal haemoglobin levels will not improve outcome

Recent evidence suggests that critically ill patients are able to tolerate lower levels of haemoglobin than was previously believed. It is our goal to show that transfusing to a level of 100 g/l does not improve mortality and other clinically important outcomes in a critical care setting. Although many questions remain, many laboratory and clinical studies, including a recent randomized controlled trial (RCT), have established that transfusing to normal haemoglobin concentrations does not improve organ failure and mortality in the critically ill patient. In addition, a restrictive transfusion strategy will reduce exposure to allogeneic transfusions, result in more efficient use of red blood cells (RBCs), save blood overall, and decrease health care costs.     

Debate: Transfusing to normal haemoglobin levels will not improve outcome

Recent evidence suggests that critically ill patients are able to tolerate lower levels of haemoglobin than was previously believed. It is our goal to show that transfusing to a level of 100 g/l does not improve mortality and other clinically important outcomes in a critical care setting. Although many questions remain, many laboratory and clinical studies, including a recent randomized controlled trial (RCT), have established that transfusing to normal haemoglobin concentrations does not improve organ failure and mortality in the critically ill patient. In addition, a restrictive transfusion strategy will reduce exposure to allogeneic transfusions, result in more efficient use of red blood cells (RBCs), save blood overall, and decrease health care costs.     

Metabolomics of ADSOL (AS-1) Red Blood Cell Storage

Population-based investigations suggest that red blood cells (RBCs) are therapeutically effective when collected, processed, and stored for up to 42 days under validated conditions before transfusion. However, some retrospective clinical studies have shown worse patient outcomes when transfused RBCs have been stored for the longest times. Furthermore, studies of RBC persistence in the circulation after transfusion have suggested that considerable donor-to-donor variability exists and may affect transfusion efficacy. To understand the limitations of current blood storage technologies and to develop approaches to improve RBC storage and transfusion efficacy, we investigated the global metabolic alterations that occur when RBCs are stored in AS-1 (AS1-RBC). Leukoreduced AS1-RBC units prepared from 9 volunteer research donors (12 total donated units) were serially sampled for metabolomics analysis over 42 days of refrigerated storage. Samples were tested by gas chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry, and specific biochemical compounds were identified by comparison to a library of purified standards. Over 3 experiments, 185 to 264 defined metabolites were quantified in stored RBC samples. Kinetic changes in these biochemicals confirmed known alterations in glycolysis and other pathways previously identified in RBCs stored in saline, adenine, glucose and mannitol solution (SAGM-RBC). Furthermore, we identified additional alterations not previously seen in SAGM-RBCs (eg, stable pentose phosphate pathway flux, progressive decreases in oxidized glutathione), and we delineated changes occurring in other metabolic pathways not previously studied (eg, S-adenosyl methionine cycle). These data are presented in the context of a detailed comparison with previous studies of SAGM-RBCs from human donors and murine AS1-RBCs. Global metabolic profiling of AS1-RBCs revealed a number of biochemical alterations in stored blood that may affect RBC viability during storage as well as therapeutic effectiveness of stored RBCs in transfusion recipients. These results provide future opportunities to more clearly pinpoint the metabolic defects during RBC storage, to identify biomarkers for donor screening and prerelease RBC testing, and to develop improved RBC storage solutions and methodologies.     

Pulmonary effects of red blood cell transfusion in critically ill,non‐bleeding patients

The aim of the study is to evaluate the effects of red blood cell (RBC) transfusions on pulmonary parameters in critically ill, non‐bleeding patients. Retrospective chart analysis was performed on critically ill patients without overt bleeding in the intensive care unit (ICU) of a university hospital. In 83 patients in a 5‐month period, who had received at least 1 RBC unit and stayed at least 24 h in the ICU, 199 transfusions of median 2 RBCs per transfusion (n = 504) were studied. Pulmonary parameters were retrieved during the period between 24 h before the start of transfusion and 24–48 h after transfusion. Outcome was assessed. The P_aO₂/F_IO₂ dose‐dependently decreased from 250 ± 105 at baseline to 240 ± 102 mmHg at 24 h after RBC transfusion (P = 0·003), irrespective of acute lung injury at baseline and RBC storage time. The lung injury score (LIS) also increased dose‐dependently, whereas, at 48 h, oxygenation and LIS largely returned to baseline. For every seven RBCs transfused, the LIS transiently increased by 1 unit. There were no changes in haemodynamics, lung mechanics or chest radiography. The total number of RBCs given in the ICU did not directly contribute to ICU and 1‐year mortality prediction. Transfusion of RBCs decreases oxygenation thereby increasing the LIS, dose‐dependently and transiently, in a heterogeneous population of critically ill, non‐bleeding patients, independent of prior cardiorespiratory status and RBC storage time. The effects are subtle, may go unseen and unreported and may represent subclinical transfusion‐related acute lung injury. They do not adversely affect outcome, even at 1‐year follow‐up.     

Anemia in the critically ill

The anemia of critical illness is a distinct clinical entity with characteristics similar to that of chronic disease anemia. Several solutions to the processes of anemia, such as blunted erythropoietin production and erythropoietin response and abnormalities in iron metabolism have been developed. The transfusion of RBCs provides immediate correction of low hemoglobin levels, which may be of value in patients with life-threatening anemia. Avoidance of RBC and blood component transfusion, however, is becoming increasingly important as data of adverse clinical outcomes in critically ill patients become clearer. Although the optimal hemoglobin in critically ill patients is not determined, this organ system has a generous reserve. Short-term compensated anemia is tolerated well, while exogenous erythropoietin allows patients to achieve higher hemoglobin concentrations without exposure to transfused blood/blood components. A recent randomized trial enrolled over 1300 critically ill patients to receive either 40,000 units of exogenous erythropoietin or placebo. These authors found that patients randomized to erythropoietin received significantly less allogeneic RBC transfusions and had significantly greater increases in hemoglobin. Although no differences were found between groups in gross clinical outcomes (ie, death, renal failure, myocardial infarction), this study did not have the power to identify small differences in outcomes. This and other studies of exogenous erythropoietin therapy in critically ill patients clearly demonstrate that the bone marrow in many of these patients will respond to the administration of erythropoietin despite their illness, suggesting a blunted production of erythropoietin rather than a blunted response to erythropoietin. Exogenous erythropoietin therefore represents a therapeutic option for treating anemia in critical illness. Acute events in medicine and surgery often lead to many patients becoming anemic. Solutions to this process of anemia should be focused on preventing such events. Anemia after surgery represents an area for prevention. Blood conservation strategies can be performed with adequate results. Monk et al randomized 79 patients undergoing radical prostatectomy to preoperative autologous donation (PAD), preoperative exogenous erythropoietin therapy plus ANH immediately following induction of general anesthesia, and ANH alone. This study concluded that all three techniques resulted in similar hemostasis outcomes (eg, bleeding and transfusion rates), but ANH alone was the least expensive, and ANH plus exogenous erythropoietin and ANH alone resulted in a higher ICU hematocrit compared with PAD. Regardless of these prophylactic strategies, patients still become anemic after surgery or during critical illness. This acute event anemia usually is treated with RBC transfusion; however, autologous blood recovery (cell salvage systems) has been shown to be effective in patients with acute bleeding-related anemia, and this may reduce patients' exposure to allogeneic blood in these patients. There are no universally accepted treatment guidelines for managing anemia, and practice differs between clinicians, hospitals, regions, and countries. Transfusion medicine is evolving and incorporating many new pharmacological agents into the armamentarium of anemia and bleeding therapy. Accumulating evidence suggests that anemia in critically ill patients is common and correlated with poor outcomes. The management of anemia can improve outcomes; however, the optimal management of anemia is not performed universally. New approaches, continued research, and an understanding of anemia may result in more consistent and improved outcomes for critically ill patients.     

Adverse blood transfusion outcomes: establishing causation

The transfusion of allogeneic red blood cells (RBCs) and other blood components is ingrained in modern medical practice. The rationale for administering transfusions is based on key assumptions that efficacy is established and risks are acceptable and minimized. Despite the cliché that, "the blood supply is safer than ever," data about risks and lack of efficacy of RBC transfusions in several clinical settings have steadily accumulated. Frequentist statisticians and clinicians demand evidence from randomized clinical trials (RCTs); however, causation for the recognized serious hazards of allogeneic transfusion has never been established in this manner. On the other hand, the preponderance of evidence implicating RBC transfusions in adverse clinical outcomes related to immunomodulation and the storage lesion comes from observational studies, and a broad and critical analysis to evaluate causation is overdue. It is suggested in several circumstances that this cannot wait for the design, execution, and conduct of rigorous RCTs. We begin by examining the nature and definition of causation with relevant examples from transfusion medicine. Deductive deterministic methods may be applied to most of the well-accepted and understood serious hazards of transfusion, with modified Koch's postulates being fulfilled in most circumstances. On the other hand, when several possible interacting risk factors exist and RBC transfusions are associated with adverse clinical outcomes, establishing causation requires inferential probabilistic methodology. In the latter circumstances, the case for RBC transfusions being causal for adverse clinical outcomes can be strengthened by applying modified Bradford Hill criteria to the plethora of existing observational studies. This being the case, a greater precautionary approach to RBC transfusion is necessary and equipoise that justifying RCTs may become problematic.     

Duration of red blood cell storage is associated with increased incidence of deep vein thrombosis and in hospital mortality in patients with traumatic injuries

Introduction  

In critically ill patients the relationship between the storage age of red blood cells (RBCs) transfused and outcomes are controversial. To determine if duration of RBC storage is associated with adverse outcomes we studied critically ill trauma patients requiring transfusion.     

Evidence-Based Red Blood Cell Transfusion Practices in Cardiac Surgery

Cardiac surgical patients are among the highest consumers of allogeneic red blood cells (RBCs) due to the prevalence of anemia and bleeding. Up until recently, there was a paucity of high-quality evidence informing transfusion decisions in this patient group which led to wide variability in transfusion decision making. The article reviews and critically analyzes the available evidence for RBC transfusion in cardiac surgery, focusing on trials of transfusion triggers and age of blood, and provides suggestions for future research. Observational studies analyzing outcomes in patients transfused vs those not transfused have consistently shown RBC transfusion to be associated with adverse outcomes. However, multiple sources of bias in these studies invalidate their conclusions. The best available evidence comes from randomized controlled trials which compare liberal vs restrictive transfusion thresholds. To date, 6 randomized controlled trials have been reported in cardiac surgical patients, and pooled analyses have shown no differences in clinical outcomes between the 2 strategies. Similarly, research into age of RBCs and adverse outcomes has failed to demonstrate a pathological effect attributable to the storage lesion; the recent multicenter Red Cell Storage Duration Study (RECESS) trial has demonstrated no difference in outcomes between patients receiving fresh or old RBCs. Future research needs to identify what a safe transfusion threshold may be, and how this differs for different patient groups and different stages of the perioperative journey. There is also a need to evaluate other physiological parameters which, coupled with hemoglobin concentration, can better inform those patients who need an RBC transfusion.     

Posttransfusion recovery of stored red blood cells in very low birth weight infants using a hemoglobin balance model

BACKGROUND: A Hb balance model was used in very low birth weight (VLBW) infants to predict posttransfusion Hb levels from which we inferred allogeneic RBC recovery after transfusion of RBCs stored for varying periods of time. STUDY DESIGN AND METHODS: Premature VLBW infants receiving RBC transfusions during the 1st month of life were evaluated retrospectively for RBC survival of stored donor blood. Actual Hb levels measured in infant blood 1 and 2 days after RBC transfusions were compared to those predicted using a Hb balance model based on factors affecting blood Hb loss and gain. Transfusions were subgrouped according to whether or not infants were clinically stable at the time of RBC transfusion. Model-predicted RBC recovery was also evaluated relative to duration of RBC storage. RESULTS: Model-predicted mean (+/- SD) Hb levels 2 days after transfusion among the 30 VLBW infants receiving a total of 57 RBC transfusions were only 4 percent higher than actual values observed (15.2 +/- 1.2 g/dL vs. 14.7 +/- 1.4, respectively; p < 0.05). The infant's clinical status at the time of transfusion did not affect predicted 1- and 2-day posttransfusion RBC recovery. Model-predicted recovery of transfused RBCs was modestly, but significantly, decreased with increasing duration of donor RBC storage (i.e., 10% lower by 42 days-the maximal allowed storage period for donor blood [p < 0.01]). CONCLUSIONS: Our model-predicted RBC survival results are consistent with-but not direct evidence of-hemolysis of donor blood after RBC transfusion. Although observed post-RBC Hb levels 2 days after transfusion averaged only 4 percent less than predicted, model-predicted survival of donor RBCs at 42 days suggested a modest decrease (i.e., by 10%).     

Transfusion of fresh murine red blood cells reverses adverse effects of older stored red blood cells

BACKGROUND: Although a subset of recent studies have suggested that red blood cell (RBC) storage length is associated with adverse patient outcomes, others have shown no such relationship. Adults may be transfused with RBC units of different storage lengths, and existing studies do not take into consideration that fresh RBCs may alter responses to concurrently transfused stored RBCs. To test this possibility, we utilized a murine model and investigated transfusion outcomes of fresh, stored, or fresh‐plus‐stored RBCs. STUDY DESIGN AND METHODS: Fresh, 14‐day‐stored or fresh plus 14‐day‐stored leukoreduced RBCs from HOD‐transgenic donors (with RBC‐specific expression of hen egg lysozyme, ovalbumin, and human Duffy^b) were transfused into naïve C57BL/6 recipients. Serum cytokines and anti‐HOD alloimmunization were evaluated after transfusion. RESULTS: In six of six experiments (n = 90 mice total), a proinflammatory serum cytokine storm of interleukin‐6, keratinocyte‐derived chemokine/CXCL1, and monocyte chemoattractant protein‐1 was observed in transfusion recipients of stored but not fresh RBCs, along with high degrees of anti‐HOD alloimmunization. However, concurrent transfusion of fresh HOD RBCs along with stored HOD RBCs significantly decreased these adverse outcomes (p < 0.05). CONCLUSIONS: These results are consistent with fresh murine HOD RBCs losing protective properties during storage, and introduce a previously unrecognized variable in RBC storage studies. If translatable to humans, uniform “old blood” groups may be needed in future clinical studies to more accurately investigate the biologic effects of older RBC units.