Prevention of potential delayed hemolytic transfusion reaction in two sickle cell patients using intravenous immunoglobulins and steroids before and after red blood cell exchange with antigen positive units and review literature.

Emergent Red Blood Cell (RBC) exchange is indicated in sickle cell disease (SCD) patients with severe acute chest syndrome. However, fully matched RBC units may not be available for patients with multiple RBC antibodies. Intravenous immunoglobulin (IVIG) and steroids were reported for preventing potential delayed hemolytic transfusion reaction (HTR) in simple transfusion of antigen-positive RBCs. We investigated the efficacy and safety of IVIG and steroids in two SCD patients presented with acute chest syndrome receiving RBC exchange with multiple incompatible units. The first patient had multiple historical alloantibodies, including anti-Jsb, although none of them were reactive. IVIG (1 g/kg) was given before and after RBC exchange with methylprednisolone (500 mg IV) one hour before exchange. Her sickle hemoglobin (HbS) was reduced from 89.4% to 17.4% after the exchange with five Jsb-positive units. The patient improved clinically without acute or delayed hemolysis. The second patient had reactive anti-Jsb on two different admissions 18 months apart. Only one of the sixteen units used in the exchanges was Jsb negative. He received the same IVIG regimen during both admissions but 100 mg IV hydrocortisone instead of methylprednisolone. His HbS was reduced from 63.4% to 22.4% after the first exchange. Significant clinical improvements were achieved after both exchanges. No delayed HTR was observed. Our experience of these two patients suggested that IVIG and steroids may be used in preventing potential delayed HTR in some SCD patients with rare antibodies receiving large amounts of antigen-positive RBC products.

Utility of hemoglobin electrophoresis to distinguish between severe delayed hemolytic transfusion reaction versus hyperhemolysis syndrome.

Delayed hemolytic transfusion reaction (DHTR) and hyperhemolysis syndrome (HHS) are both complications of red blood cell transfusions in patients with sickle cell disease.Clinically, both present with hemolysis and can be difficult to differentiate. Hemoglobin electrophoresis may aid in the diagnosis. Herein we describe a case in which a patient with hemoglobin SC disease presented with features of severe hemolysis several days after initiation of red blood cell exchange. Increase in reticulocyte count and complete absence of hemoglobin A on electrophoresis during this event supported the diagnosis of severe DHTR, indicating a rapid and selective destruction of the transfused red blood cells. Ability to interpret the hemoglobin electrophoresis can help clinicians distinguish between these two severe transfusion complications in patients living with sickle cell disease. It is important to identify the presence or absence of concomitant HHS, as patients with HHS tend to have a worse prognosis and there is a higher rate of recurrence of HHS with subsequent transfusions. Accurate diagnosis can lead to prompt management and decrease morbidity and mortality.

Advancing in vivo assessment of red blood cell transfusions: A call for radiation-free methods in transfusion medicine.

RBC transfusions are a vital clinical therapy to treat anemic patients. The in vivo assessment of red blood cell (RBC) quality post-transfusion is critical to ensuring that the introduction of new RBC products meet established regulatory and clinical quality requirements. Although in vitro quality control testing is routinely performed by blood manufacturers, it is crucial that in vivo tests are performed during the evaluation and regulatory process of new RBC products. This article reviews existing in vivo techniques, like chromium-51 labelling and biotinylation, for determining the circulation and survival of RBCs, and advocates for a move to radiation-free methods. The timely need for radiation-free methods to assess emerging non-DEHP container systems is just one example of why efforts to improve the methods available for in vivo quality assessment is important in transfusion medicine. This review aims to advance our understanding of RBC transfusion in vivo quality assessment and enhance transfusion practices.

A perspective on exogenous redox regulation mediated by transfused RBCs subject to the storage lesion.

Granted with a potent ability to interact with and tolerate oxidative stressors, RBCs scavenge most reactive oxygen and nitrogen species (RONS) generated in circulation. This essential non-canonical function, however, renders RBCs susceptible to damage when vascular RONS are generated in excess, making vascular redox imbalance a common etiology of anemia, and thus a common indication for transfusion. This accentuates the relevance of impairments in redox metabolism during hypothermic storage, as the exposure to chronic oxidative stressors upon transfusion could be exceedingly deleterious to stored RBCs. Herein, we review the prominent mechanisms of the hypothermic storage lesion that alter the ability of RBCs to scavenge exogenous RONS as well as the associated clinical relevance.

Optimization of single-needle red cell exchange in patients with sickle cell disease.

The hypercoagulable state associated with sickle cell disease (SCD) can be challenging for apheresis procedures. Among 62 single-needle red cell exchanges (SN-RCEs) performed over a 15-month period, 4 patients experienced 6 hemolytic events with a discolored plasma layer, elevated plasma/RBC interface in the centrifuge, and accompanying alarms of "Cells were detected in plasma line from centrifuge" or "AIM system detected RBC at top of connector." The hemolysis originated from the apheresis instrument because samples from the apheresis belt but not the patients' peripheral blood were positive for hemolysis. Further analysis showed the alarms occurred more often in SN-RCEs (20.4%) than double-needle RCEs (2.7%), and the hemolysis was probably secondary to clumping. To optimize SN-RCE, we increased the anticoagulant dosage by changing Inlet/AC ratio from 13 to 8 and lowered the inlet rate to the level comparable to double-needle RCE. The adjustments were well-tolerated with no more hemolysis.

Effect of Minimization of Early Blood Sampling Losses Among Extremely Premature Neonates: A Randomized Clinical Trial.

OBJECTIVE: To evaluate the effect of blood sampling stewardship on transfusion requirements among infants born extremely preterm. STUDY DESIGN: In this single-center, randomized controlled trial (RCT), infants born at <28 weeks of gestation and birth weight of <1000 g were randomized at 24 hours of age to two different blood sampling approaches: restricted sampling (RS) vs conventional sampling (CS). The stewardship intervention in the RS group included targeted reduction in blood sampling volume and frequency and point of care testing methods in the first 6 weeks after birth. Both groups received early recombinant erythropoietin from day three of age. Primary outcome was the rate of early red blood cell (RBC) transfusions in the first six postnatal weeks. RESULTS: A total of 102 infants (mean gestational age: 26 weeks; birth weight: 756 g) were enrolled. Fidelity to the sampling protocol was achieved in 95% of the infants. Sampling losses in the first 6 weeks were significantly lower in the RS group (16.8 ml/kg vs 23.6 ml/kg, P < .001). The RS group had a significantly lower rate of early postnatal RBC transfusions (41% vs 73%, RR: 0.56 [0.39-0.81], P = .001). The hazard of needing a transfusion during neonatal intensive care unit (NICU) stay was reduced by 55% by RS. Mortality and neonatal morbidities were similar between the two groups. CONCLUSION: Minimization of blood sampling losses by approximately one-third in the first 6 weeks after birth leads to substantial reduction in the early red blood cell transfusion rate in infants born extremely preterm and weighing <1000 g at birth. TRIAL REGISTRATION: http://www.ctri.nic.in (CTRI/2020/01/022  964).

Current concepts in the use of cell salvage in obstetrics.

PURPOSE OF REVIEW: The worldwide leading cause of maternal death is severe maternal hemorrhage. Maternal hemorrhage can be profound leading to an entire loss of blood volume. In the past two decades, Patient Blood Management has evolved to improve patient's care and safety. In surgeries with increased blood loss exceeding 500 ml, the use of cell salvage is strongly recommended in order to preserve the patient's own blood volume and to minimize the need for allogeneic red blood cell (RBC) transfusion. In this review, recent evidence and controversies of the use of cell salvage in obstetrics are discussed. RECENT FINDINGS: Numerous medical societies as well as national and international guidelines recommend the use of cell salvage during maternal hemorrhage. SUMMARY: Intraoperative cell salvage is a strategy to maintain the patient's own blood volume and decrease the need for allogeneic RBC transfusion. Historically, cell salvage has been avoided in the obstetric population due to concerns of iatrogenic amniotic fluid embolism (AFE) or induction of maternal alloimmunization. However, no definite case of AFE has been reported so far. Cell salvage is strongly recommended and cost-effective in patients with predictably high rates of blood loss and RBC transfusion, such as women with placenta accreta spectrum disorder. However, in order to ensure sufficient practical experience in a multiprofessional obstetric setting, liberal use of cell salvage appears advisable.

Impact of peri-operative red blood cell transfusions for treatment of anemia on acute rejection in renal transplant recipients.

INTRODUCTION: Anemia occurs before and after kidney transplantation. Determining the impact of perioperative transfusion on post-transplant outcomes can help determine best management of anemia. PROJECT AIM: The current study aims to describe clinical outcomes associated with packed red blood cell transfusions in the peri-operative management of anemia after transplantation. DESIGN: This was a single-center, retrospective study of adult kidney recipients with anemia at the time of transplantation. 1271 patients were stratified by donor-type due to the potential variability in underlying recipient and transplant characteristics; living donor (n = 698, 62%) or deceased donor (n = 573, 38%). RESULTS: Living donor recipients that received blood during the index hospitalization were more likely to experience rejection within 30 days (18% vs. 10%, p = 0.008) and 1 year of transplant (32% vs. 16%, p = 0.038). In multivariate analysis, receiving both blood and darbepoetin (HR: 1.89 [1.20,3.00], p = 0.006), age at transplant (HR: 0.98 [0.97, 0.99], p = 0.02), number of HLA mismatches (HR: 1.17 [1.05,1.30], p = 0.003), and whether the case was a repeat transplant (HR: 2.77 [1.93,3.97], p < 0.01) were significantly associated with hazard of rejection. For deceased donor recipients, there were no differences in acute rejection, graft failure or mortality at 30 days or 1 year. When analyzing hazard of rejection in a multivariate model, treatment received was not found to be significantly associated with rejection. CONCLUSION: Our findings suggest there may be a role for more aggressive pre-transplant treatment of anemia for those patients undergoing living donor transplants.

Red cell transfusion thresholds in outpatients with myelodysplastic syndromes: Results of a pilot randomized trial RBC-ENHANCE.

BACKGROUND: The optimal hemoglobin (Hb) threshold for red blood cell transfusions in adult patients with myelodysplastic syndromes (MDS) has not been defined. STUDY DESIGN AND METHODS: We conducted a pilot randomized multi-center study of two transfusion algorithms (liberal, to maintain Hb 110-120 g/L, transfuse 2 units if Hb < 105 g/L and 1 unit if Hb 105-110 g/L vs. restrictive, 85-105 g/L, transfuse 2 units when Hgb < 85 g/L). Primary objectives were 70% compliance in maintaining the q2 week hemoglobin within the targeted range and the achievement of a 15 g/L difference in pre-transfusion Hb. Secondary outcomes included measures of quality of life (QOL), iron studies and safety. RESULTS: Twenty-eight patients were randomized between February 2015-2020, 13 to the restrictive arm and 15 to the liberal arm in three tertiary care centers. The compliance was 66% and 45% and the mean pre-transfusion Hb thresholds were 86 (standard deviation [SD] 8) and 98 g/L (SD 10) in the restrictive and liberal arms, (mean difference 11.8 g/L, p < .0001), respectively. Patients in the liberal arm experienced a mean of 3.4 (SD 2.6) more transfusion visits and received a mean of 5.3 (SD 5.5) more units of blood during the 12-week study. Ferritin increased by 1043 (SD 1516) IU/L and 148 (SD 1319) IU/L in the liberal and restrictive arms, respectively. Selected QOL scores were superior pre-transfusion and more patients achieved clinically important improvements in the liberal arm compared with the restrictive arm for selected symptoms and function domains. CONCLUSION: The results establish that policies for transfusion support can be delivered in practice at multiple hospitals, but further research is required to understand the full clinical effects and safety of liberal transfusion policies in MDS outpatients.

Association of initial lactate levels and red blood cell transfusion strategy with outcomes after severe trauma: a post hoc analysis of the RESTRIC trial.

BACKGROUND: The appropriateness of a restrictive transfusion strategy for those with active bleeding after traumatic injury remains uncertain. Given the association between tissue hypoxia and lactate levels, we hypothesized that the optimal transfusion strategy may differ based on lactate levels. This post hoc analysis of the RESTRIC trial sought to investigate the association between transfusion strategies and patient outcomes based on initial lactate levels. METHODS: We performed a post hoc analysis of the RESTRIC trial, a cluster-randomized, crossover, non-inferiority multicenter trials, comparing a restrictive and liberal red blood cell transfusion strategy for adult trauma patients at risk of major bleeding. This was conducted during the initial phase of trauma resuscitation; from emergency department arrival up to 7 days after hospital admission or intensive care unit (ICU) discharge. Patients were grouped by lactate levels at emergency department arrival: low (< 2.5 mmol/L), middle (≥ 2.5 and < 4.0 mmol/L), and high (≥ 4.0 mmol/L). We compared 28 days mortality and ICU-free and ventilator-free days using multiple linear regression among groups. RESULTS: Of the 422 RESTRIC trial participants, 396 were analyzed, with low (n = 131), middle (n = 113), and high (n = 152) lactate. Across all lactate groups, 28 days mortality was similar between strategies. However, in the low lactate group, the restrictive approach correlated with more ICU-free (ß coefficient 3.16; 95% CI 0.45 to 5.86) and ventilator-free days (ß coefficient 2.72; 95% CI 0.18 to 5.26) compared to the liberal strategy. These findings persisted even after excluding patients with severe traumatic brain injury. CONCLUSIONS: Our results suggest that restrictive transfusion strategy might not have a significant impact on 28-day survival rates, regardless of lactate levels. However, the liberal transfusion strategy may lead to shorter ICU- and ventilator-free days for patients with low initial blood lactate levels.

Euvolemic automated transfusion to treat severe anemia in sickle cell disease patients at risk of circulatory overload.

BACKGROUND: Red blood cell (RBC) transfusion remains a major treatment for sickle cell disease (SCD). Patients with SCD have a high prevalence of renal impairment and cardiorespiratory disease, conferring risk of transfusion-associated circulatory overload (TACO). STUDY DESIGN AND METHODS: We describe an approach, titled euvolemic automated transfusion (EAT), to transfuse SCD patients with severe anemia who are at risk of TACO. In EAT, plasmapheresis is performed using donor RBCs, rather than albumin or plasma, as replacement fluid. Euvolemia is maintained. A retrospective analysis was conducted of patients with SCD who underwent EAT at our institution over a 10-year period, to evaluate the efficacy and safety of EAT. RESULTS: Eleven SCD patients underwent 109 EAT procedures (1-59 procedures per patient). The median age was 42 years (IQR = [30-49]) and 82% (n = 9) were female. Most (82%; n = 9) patients had severe chronic kidney disease and 55% (n = 6) had heart failure. One (9%) patient had a history of life-threatening TACO. Mean pre- and post-procedure Hct values were 19.8% (SD ± 1.6%) and 29.1% (SD ± 1.4%), respectively. The average Hct increment was 3.2% per RBC unit. Only two EAT-related complications were recorded during the 109 procedures: central line-associated infection and citrate toxicity (muscle cramping). EAT used an average of two RBC units less than that projected for standard automated RBC exchange. CONCLUSION: Our findings suggest that EAT is safe and effective to treat patients with SCD and severe anemia, who are at risk for TACO. EAT requires fewer RBC units compared to automated RBC exchange.

Optimal dose of cryoprecipitate in massive transfusion following trauma.

BACKGROUND: While cryoprecipitate (Cryo) is commonly included in massive transfusion protocols for hemorrhagic shock, the optimal dose of Cryo transfusion remains unknown. We evaluated the optimal red blood cell (RBC) to RBC to Cryo ratio during resuscitation in massively transfused trauma patients. METHODS: Adult patients in the American College of Surgeon Trauma Quality Improvement Program (2013-2019) receiving massive transfusion (≥4 U of RBCs, ≥1 U of fresh frozen plasma, and ≥1 U of platelets within 4 hours) were included. A unit of Cryo was defined as a pooled unit of 100 mL. The RBC:Cryo ratio was calculated for blood products transfused within 4 hours of presentation. The association between RBC:Cryo and 24-hour mortality was analyzed with multivariable logistic regression adjusting for the volume of RBC, plasma and platelet transfusions, global and regional injury severity, and other relevant variables. RESULTS: The study cohort included 12,916 patients. Among those who received Cryo (n = 5,511 [42.7%]), the median RBC and Cryo transfusion volume within 4 hours was 11 U (interquartile range, 7-19 U) and 2 U (interquartile range, 1-3 U), respectively. Compared with no Cryo administration, only RBC:Cryo ratios ≤8:1 were associated with a significant survival benefit, while lower doses of Cryo (RBC:Cryo >8:1) were not associated with decreased 24-hour mortality. Compared with the maximum dose of Cryo administration (RBC:Cryo, 1:1-2:1), there was no difference in 24-hour mortality up to RBC:Cryo of 7:1 to 8:1, whereas lower doses of Cryo (RBC:Cryo, >8:1) were associated with significantly increased 24-hour mortality. CONCLUSION: One pooled unit of Cryo (100 mL) per 7 to 8 U of RBCs could be the optimal dose of Cryo in trauma resuscitation that provides a significant survival benefit while avoiding unnecessary blood product transfusions. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level IV.

Blood Product Transfusions for Children in the Perioperative Period and for Critically Ill Children.

BACKGROUND: Approximately 1% to 2% of all hospitalized children receive a transfusion of blood products, in Germany as in other countries. High-quality scientific evidence on transfusions in children is scarce. The available evidence is discussed in this review. METHODS: This review is based on publications on blood product transfusions in children that were retrieved by a literature search, including clinical studies, international guideline recommendations, the recommendations of the German cross-sectional guideline, and results of other recent, relevant publications. RESULTS: A restrictive transfusion strategy is recommended for all children, including those who are critically ill. Randomized controlled trials have shown that a restrictive strategy for erythrocyte concentrate transfusion in the intensive care unit is safe for children, including neonates. No robust data are available to enable the definition of a suitable threshold for the intraoperative administration of red blood cell concentrates in children undergoing extracardiac surgery. On the basis of studies from pediatric intensive care units, transfusions for hemodynamically stable children with a hemoglobin concentration of more than 7 g/dL are recommended only in exceptional cases. Therapeutic plasma is not recommended as volume replacement, except in massive transfusion. Platelet concentrate transfusions are indicated in case of active hemorrhage, and only rarely for prophylaxis. CONCLUSION: There is a broad lack of evidence from randomized controlled trials concerning the indications for transfusions in children. A restrictive transfusion strategy, which has been found safe in the intensive-care setting, is favored by the guidelines in the perioperative setting as well. Further studies are needed to evaluate transfusion triggers and indications for all types of blood products, especially therapeutic plasma. Until more evidence is available, physicians should be aware of what the current evidence supports, and blood products should be given restrictively, and not prophylactically.

Maintaining a whole blood-centered transfusion improves survival in hemorrhagic resuscitation.

BACKGROUND: Whole blood (WB) transfusion has been shown to improve mortality in trauma resuscitation. The optimal ratio of packed red blood cells (pRBC) to WB in emergent transfusion has not been determined. We hypothesized that a low pRBC/WB transfusion ratio is associated with improved survival in trauma patients. METHODS: We analyzed the 2021 Trauma Quality Improvement Program (TQIP) database to identify patients who underwent emergent surgery for hemorrhage control and were transfused within 4 hours of hospital arrival, excluding transfers or deaths in the emergency department. We stratified patients based on pRBC/WB ratios. The primary outcome was mortality at 24 hours. Logistic regression was performed to estimate odds of mortality among ratio groups compared with WB alone, adjusting for injury severity, time to intervention, and demographics. RESULTS: Our cohort included 17,562 patients; of those, 13,678 patients had only pRBC transfused and were excluded. Fresh frozen plasma/pRBC ratio was balanced in all groups. Among those who received WB (n = 3,884), there was a significant increase in 24-hour mortality with higher pRBC/WB ratios (WB alone 5.2%, 1:1 10.9%, 2:1 11.8%, 3:1 14.9%, 4:1 20.9%, 5:1 34.1%, p = 0.0001). Using empirical cutpoint estimation, we identified a 3:1 ratio or less as an optimal cutoff point. Adjusted odds ratios of 24-hour mortality for 4:1 and 5:1 groups were 2.85 (95% confidence interval [CI], 1.19-6.81) and 2.89 (95% CI, 1.29-6.49), respectively. Adjusted hazard ratios of 24-hour mortality were 2.83 (95% CI, 1.18-6.77) for 3:1 ratio, 3.67 (95% CI, 1.57-8.57) for 4:1 ratio, and 1.97 (95% CI, 0.91-4.23) for 5:1 ratio. CONCLUSION: Our analysis shows that higher pRBC/WB ratios at 4 hours diminished survival benefits of WB in trauma resuscitation. Further efforts should emphasize this relationship to optimize trauma resuscitation protocols. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

The selection and preparation of red cell components for intrauterine transfusion: A national survey.

BACKGROUND AND OBJECTIVES: The practice regarding the selection and preparation of red blood cells (RBCs) for intrauterine transfusion (IUT) is variable reflecting historical practice and expert opinion rather than evidence-based recommendations. The aim of this survey was to assess Canadian hospital blood bank practice with respect to red cell IUT. MATERIALS AND METHODS: A survey was sent to nine hospital laboratories known to perform red cell IUT. Questions regarding component selection, processing, foetal pre-transfusion testing, transfusion administration, documentation and traceability were assessed. RESULTS: The median annual number of IUTs performed in Canada was 109 (interquartile range, 103-118). RBC selection criteria included allogeneic, Cytomegalovirus seronegative, irradiated, fresh units with most sites preferentially providing HbS negative, group O, RhD negative, Kell negative and units lacking the corresponding maternal antibody without extended matching to the maternal phenotype. Red cell processing varied with respect to target haematocrit, use of saline reconstitution (n = 4), use of an automated procedure for red cell concentration (n = 1) and incorporation of a wash step (n = 2). Foetal pre-transfusion testing uniformly included haemoglobin measurement, but additional serologic testing varied. A variety of strategies were used to link the IUT event to the neonate post-delivery, including the creation of a unique foetal blood bank identifier at three sites. CONCLUSION: This survey reviews current practice and highlights the need for standardized national guidelines regarding the selection and preparation of RBCs for IUT. This study has prompted a re-examination of priorities for RBC selection for IUT and highlighted strategies for transfusion traceability in this unique setting.

Reevaluation of the medical necessity of washed red blood cell transfusion in chronically transfused adults.

BACKGROUND: Washing red blood cell (RBC) units mitigates severe allergic transfusion reactions. However, washing reduces the time to expiration and the effective dose. Automated washing is time- and labor-intensive. A shortage of cell processor tubing sets prompted review of medical necessity for washed RBC for patients previously thought to require washing. STUDY DESIGN AND METHODS: A single-center, retrospective study investigated discontinuing wash RBC protocols in chronically transfused adults. In select patients with prior requirements for washing, due to a history of allergic transfusion reactions, trials of unwashed transfusions were performed. Patient demographic, clinical, laboratory, and transfusion data were compiled. The per-unit washing cost was the sum of the tubing set, saline, and technical labor costs. RESULTS: Fifteen patients (median age 34 years interquartile range [IQR] 23-53 years, 46.7% female) were evaluated. These patients had been transfused with a median of 531 washed RBC units (IQR 244-1066) per patient over 12 years (IQR 5-18 years), most commonly for recurrent, non-severe allergic reactions. There were no transfusion reactions with unwashed RBCs aside from one patient with one episode of pruritus and another with recurrent pruritus, which was typical even with washed RBC. We decreased the mean number of washed RBC units per month by 72.9% (104 ± 10 vs. 28.2 ± 25.2; p < .0001) and saved US $100.25 per RBC unit. CONCLUSION: Washing of RBCs may be safely reconsidered in chronically transfused patients without a history of anaphylaxis. Washing should be implemented judiciously due to potential lack of necessity and logistical/operational challenges.

Restrictive or Liberal Transfusion Strategy in Myocardial Infarction and Anemia.

BACKGROUND: A strategy of administering a transfusion only when the hemoglobin level falls below 7 or 8 g per deciliter has been widely adopted. However, patients with acute myocardial infarction may benefit from a higher hemoglobin level. METHODS: In this phase 3, interventional trial, we randomly assigned patients with myocardial infarction and a hemoglobin level of less than 10 g per deciliter to a restrictive transfusion strategy (hemoglobin cutoff for transfusion, 7 or 8 g per deciliter) or a liberal transfusion strategy (hemoglobin cutoff, <10 g per deciliter). The primary outcome was a composite of myocardial infarction or death at 30 days. RESULTS: A total of 3504 patients were included in the primary analysis. The mean (±SD) number of red-cell units that were transfused was 0.7±1.6 in the restrictive-strategy group and 2.5±2.3 in the liberal-strategy group. The mean hemoglobin level was 1.3 to 1.6 g per deciliter lower in the restrictive-strategy group than in the liberal-strategy group on days 1 to 3 after randomization. A primary-outcome event occurred in 295 of 1749 patients (16.9%) in the restrictive-strategy group and in 255 of 1755 patients (14.5%) in the liberal-strategy group (risk ratio modeled with multiple imputation for incomplete follow-up, 1.15; 95% confidence interval [CI], 0.99 to 1.34; P = 0.07). Death occurred in 9.9% of the patients with the restrictive strategy and in 8.3% of the patients with the liberal strategy (risk ratio, 1.19; 95% CI, 0.96 to 1.47); myocardial infarction occurred in 8.5% and 7.2% of the patients, respectively (risk ratio, 1.19; 95% CI, 0.94 to 1.49). CONCLUSIONS: In patients with acute myocardial infarction and anemia, a liberal transfusion strategy did not significantly reduce the risk of recurrent myocardial infarction or death at 30 days. However, potential harms of a restrictive transfusion strategy cannot be excluded. (Funded by the National Heart, Lung, and Blood Institute and others; MINT ClinicalTrials.gov number, NCT02981407.).

The impact of anemia and blood transfusion on mortality after open abdominal surgery in the elderly.

BACKGROUND: Major abdominal surgery is associated with considerable mortality in the elderly. Anemia has been linked to increased mortality in other types of surgery, such as hip and cardiac surgery. This study aimed to assess the impact of preoperative anemia on mortality in the elderly undergoing major abdominal surgery, and how allogeneic red cell blood transfusion influences mortality in these patients. MATERIALS AND METHODS: We conducted a single-center, register-based retrospective study on patients, who were aged beyond 60 years and underwent one of 81 open abdominal surgical procedures. Patients operated on during the period from January 1, 2000, to May 31, 2013, were consecutively identified in the Danish National Patient Registry. Plasma hemoglobin was measured within 30 days prior to surgery and the primary endpoint was 30-day postoperative mortality. Information about patient transfusions from the hospital blood bank was available from 1998 to 2010. RESULTS: A total of 3199 patients were included of whom 85% underwent emergency surgery. The total mortality after 30 days was 20%. The median preoperative hemoglobin value of survivors was 7.7 mmol/L vs 6.9 mmol/L in those who died. The difference in hemoglobin values, between those who survived or died, decreased from the pre- to the post-operative phase. The 30-day postoperative mortality was 28%, 20%, and 12% in patients with a preoperative hemoglobin level in the lower, median, and upper quartile respectively. Transfusion therapy was associated with higher postoperative mortality, except in patients with very low hemoglobin values. CONCLUSION: Preoperative anemia has a clear association with surgically related mortality. The distribution of hemoglobin values in patients with a fatal outcome differs significantly from that of survivors. Red cell transfusion is associated with increased mortality, except in patients with very low hemoglobin values which supports recent guidelines suggesting a restrictive transfusion strategy.

Transfusion of female blood in a rat model is associated with red blood cells entrapment in organs.

Transfusion of red blood cells (RBCs) has been associated with adverse outcomes. Mechanisms may be related to donor sex and biological age of RBC. This study hypothesized that receipt of female blood is associated with decreased post-transfusion recovery (PTR) and a concomitant increased organ entrapment in rats, related to young age of donor RBCs. Donor rats underwent bloodletting to stimulate production of new, young RBCs, followed by Percoll fractionation for further enrichment of young RBCs based on their low density. Control donors did not undergo these procedures. Male rats received either a (biotinylated) standard RBC product or a product enriched for young RBCs, derived from either male or female donors. Controls received saline. Organs and blood samples were harvested after 24 hours. This study found no difference in PTR between groups, although only the group receiving young RBCs from females failed to reach a PTR of 75%. Receipt of both standard RBCs and young RBCs from females was associated with increased entrapment of donor RBCs in the lung, liver, and spleen compared to receiving blood from male donors. Soluble ICAM-1 and markers of hemolysis were higher in recipients of female blood compared to control. In conclusion, transfusing RBCs from female donors, but not from male donors, is associated with trapping of donor RBCs in organs, accompanied by endothelial activation and hemolysis.