Restrictive versus liberal red blood cell transfusion strategies for people with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without haematopoietic stem cell support.

BACKGROUND: An estimated one-quarter to one-half of people diagnosed with haematological malignancies experience anaemia. There are different strategies for red blood cell (RBC) transfusions to treat anaemia. A restrictive transfusion strategy permits a lower haemoglobin (Hb) level whereas a liberal transfusion strategy aims to maintain a higher Hb. The most effective and safest strategy is unknown. OBJECTIVES: To determine the efficacy and safety of restrictive versus liberal RBC transfusion strategies for people diagnosed with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without a haematopoietic stem cell transplant (HSCT). SEARCH METHODS: We searched for randomised controlled trials (RCTs) and non-randomised studies (NRS) in MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1982), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2023, Issue 2), and eight other databases (including three trial registries) to 21 March 2023. We also searched grey literature and contacted experts in transfusion for additional trials. There were no language, date or publication status restrictions. SELECTION CRITERIA: We included RCTs and prospective NRS that evaluated restrictive versus liberal RBC transfusion strategies in children or adults with malignant haematological disorders receiving intensive chemotherapy or radiotherapy, or both, with or without HSCT. DATA COLLECTION AND ANALYSIS: Two authors independently screened references, full-text reports of potentially relevant studies, extracted data from the studies, and assessed the risk of bias. Any disagreement was discussed and resolved with a third review author. Dichotomous outcomes were presented as a risk ratio (RR) with a 95% confidence interval (CI). Narrative syntheses were used for heterogeneous outcome measures. Review Manager Web was used to meta-analyse the data. Main outcomes of interest included: all-cause mortality at 31 to 100 days, quality of life, number of participants with any bleeding, number of participants with clinically significant bleeding, serious infections, length of hospital admission (days) and hospital readmission at 0 to 3 months. The certainty of the evidence was assessed using GRADE. MAIN RESULTS: Nine studies met eligibility; eight RCTs and one NRS. Six hundred and forty-four participants were included from six completed RCTs (n = 560) and one completed NRS (n = 84), with two ongoing RCTs consisting of 294 participants (260 adult and 34 paediatric) pending inclusion. Only one completed RCT included children receiving HSCT (n = 6); the other five RCTs only included adults: 239 with acute leukaemia receiving chemotherapy and 315 receiving HSCT (166 allogeneic and 149 autologous). The transfusion threshold ranged from 70 g/L to 80 g/L for restrictive and from 80 g/L to 120 g/L for liberal strategies. Effects were reported in the summary of findings tables only for the trials that included adults to reduce indirectness due to the limited evidence contributed by the prematurely terminated paediatric trial. Evidence from RCTs Overall, there may be little to no difference in the number of participants who die within 31 to 100 days using a restrictive compared to a liberal transfusion strategy, but the evidence is very uncertain (three studies; 451 participants; RR 1.00, 95% CI 0.27 to 3.70, P=0.99; very low-certainty evidence). There may be little to no difference in quality of life at 0 to 3 months using a restrictive compared to a liberal transfusion strategy, but the evidence is very uncertain (three studies; 431 participants; analysis unable to be completed due to heterogeneity; very low-certainty evidence). There may be little to no difference in the number of participants who suffer from any bleeding at 0 to 3 months using a restrictive compared to a liberal transfusion strategy (three studies; 448 participants; RR 0.91, 95% CI 0.78 to 1.06, P = 0.22; low-certainty evidence). There may be little to no difference in the number of participants who suffer from clinically significant bleeding at 0 to 3 months using a restrictive compared to a liberal transfusion strategy (four studies; 511 participants; RR: 0.94, 95% CI 0.74 to 1.19, P = 0.60; low-certainty evidence). There may be little to no difference in the number of participants who experience serious infections at 0 to 3 months using a restrictive compared to a liberal transfusion strategy (three studies, 451 participants; RR: 1.20, 95% CI 0.93 to 1.55, P = 0.17; low-certainty evidence). A restrictive transfusion strategy likely results in little to no difference in the length of hospital admission at 0 to 3 months compared to a liberal strategy (two studies; 388 participants; analysis unable to be completed due to heterogeneity in reporting; moderate-certainty evidence). There may be little to no difference between hospital readmission using a restrictive transfusion strategy compared to a liberal transfusion strategy (one study, 299 participants; RR: 0.89, 95% CI 0.52 to 1.50; P = 0.65; low-certainty evidence). Evidence from NRS The evidence is very uncertain whether a restrictive RBC transfusion strategy: reduces the risk of death within 100 days (one study, 84 participants, restrictive 1 death; liberal 1 death; very low-certainty evidence); or decreases the risk of clinically significant bleeding (one study, 84 participants, restrictive 3; liberal 8; very low-certainty evidence). No NRS reported on the other eligible outcomes. AUTHORS' CONCLUSIONS: Findings from this review were based on seven studies and 644 participants. Definite conclusions are challenging given the relatively few included studies, low number of included participants, heterogeneity of intervention and outcome reporting, and overall certainty of evidence. To increase the certainty of the true effect of a restrictive RBC transfusion strategy on clinical outcomes, there is a need for rigorously designed and executed studies. The evidence is largely based on two populations: adults with acute leukaemia receiving intensive chemotherapy and adults with haematologic malignancy requiring HSCT. Despite the addition of 405 participants from three RCTs to the previous review's results, there is still insufficient evidence to answer this review's primary outcome. If we assume a mortality rate of 3% within 100 days, we would need a total of 1492 participants to have an 80% chance of detecting, at a 5% level of significance, an increase in all-cause mortality from 3% to 6%. Further RCTs are needed overall, particularly in children.

Peripheral perfusion index stratifies risk in patients with intraoperative anemia: A multicentre cohort study.

STUDY OBJECTIVE: Evidence for red blood cell (RBC) transfusion thresholds in the intraoperative setting is limited, and current perioperative recommendations may not correspond with individual intraoperative physiological demands. Hemodynamics relevant for the decision to transfuse may include peripheral perfusion index (PPI). The objective of this prospective study was to assess the associations of PPI and hemoglobin levels with the risk of postoperative morbidity and mortality. DESIGN: Multicenter cohort study. SETTING: Bispebjerg and Hvidovre University Hospitals, Copenhagen, Denmark. PATIENTS: We included 741 patients who underwent acute high risk abdominal surgery or hip fracture surgery. INTERVENTIONS: No interventions were carried out. MEASUREMENTS: Principal values collected included measurements of peripheral perfusion index and hemoglobin values. METHODS: The study was conducted using prospectively obtained data on adults who underwent emergency high-risk surgery. Subjects were categorized into high vs. low subgroups stratified by pre-defined PPI levels (PPI: > 1.5 vs. < 1.5) and Hb levels (Hb: > 9.7 g/dL vs. < 9.7 g/dL). The study assessed mortality and severe postoperative complications within 90 days. MAIN RESULTS: We included 741 patients. 90-day mortality was 21% (n = 154), frequency of severe postoperative complications was 31% (n = 231). Patients with both low PPI and low Hb had the highest adjusted odds ratio for both 90-day severe postoperative complications (2.95, [1.62-5.45]) and 90-day mortality (3.13, [1.45-7.11]). A comparison of patients with low PPI and low Hb to those with high PPI and low Hb detected significantly higher 90-day mortality risk in the low PPI and low Hb group (OR 8.6, [1.57-162.10]). CONCLUSION: High PPI in acute surgical patients who also presents with anemia was associated with a significantly better outcome when compared with patients with both low PPI and anemia. PPI should therefore be further investigated as a potential parameter to guide intraoperative RBC transfusion therapy.

Adjusting Current Hemoglobin Thresholds: A Way to Improve Outcome in Women Undergoing Major Surgery.

Background/Objective: In the perioperative setting, a suboptimal total hemoglobin (Hb) mass puts women and men at an unreasonable disadvantage. Anemia is an independent risk factor for transfusion, postoperative complications, and mortality. The Hb cut-off value for women was set at <12.0 g/dL by the World Health Organization (WHO) and has been rigorously debated for decades. The aim of this study was to elucidate the risk for postoperative complications in female patients with Hb levels < 12.0, 12.0-12.9, and ≥13.0 g/dL. Material and Methods: Single-center retrospective analysis of female patients undergoing major surgery. Results: In total, 6,516 patients ≥18 years of age had major surgery between 2018 and 2019 and 2,446 female patients were included in analysis. Mean age was 67.4 ± 16.6, 66.4 ± 15.6, and 64.5 ± 15.5 years in female patients with preoperative Hb levels <12.0, 12.0-12.9 and ≥13.0 g/dL, respectively. The transfusion rate of red blood cells (RBCs) was significantly higher in female patients with Hb <12.0 g/dL (53%) and with Hb 12.0-12.9 g/dL (31%) compared to female patients ≥13.0 g/dL (22%). Rates of pneumonia, acute kidney injury, and sepsis were significantly higher in patients with Hb <12.0 and 12.0-12.9 g/dL compared to patients with Hb ≥13.0 g/dL. Total length of hospital stay was significantly longer in female patients with Hb <12.0 g/dL than patients with Hb 12.0-12.9 g/dL and Hb ≥13.0 g/dL (10 days vs. 8 days). Conclusion: Taken together, our data show that Hb values below 12.9 g/dL are associated with increased probability of RBC transfusions and increased risk of postoperative complications. In addition, our results indicate that postoperative outcomes for women might be optimized by increasing cut-off values for anemia. The call to revise the anemia threshold for women by the WHO can no longer be disregarded.

Analysis of Anemia, Transfusions, and CABG Outcomes in The Society of Thoracic Surgeons National Database.

BACKGROUND: This study characterized the association of preoperative anemia and intraoperative red blood cell (RBC) transfusion on outcomes of elective coronary artery bypass grafting (CABG). METHODS: Data from 53,856 patients who underwent CABG included in The Society of Thoracic Surgeons (STS) Adult Cardiac Database in 2019 were used. The primary outcome was operative mortality. Secondary outcomes were postoperative complications. The association of anemia with outcomes was analyzed with multivariable regression models. The influence of intraoperative RBC transfusion on the effect of preoperative anemia on outcomes was studied using mediation analysis. RESULTS: Anemia was present in 25% of patients. Anemic patients had a higher STS Predicted Risk of Operative Mortality (1.2% vs 0.7%; P < .001). Anemia was associated with operative mortality (odds ratio [OR], 1.27; 99.5% CI, 1.00-1.61; P = .047), postoperative RBC transfusion (OR, 2.28; 99.5% CI, 2.12-2.44; P < .001), dialysis (OR, 1.58; 99.5% CI, 1.19-2.11; P < .001), and prolonged intensive care unit and hospital length of stay. Intraoperative RBC transfusion largely mediated the effects of anemia on mortality (76%), intensive care unit stay (99%), and hospital stay, but it only partially mediated the association with dialysis (34.9%). CONCLUSIONS: Preoperative anemia is common in patients who undergo CABG and is associated with increased postoperative risks of mortality, complications, and RBC transfusion. However, most of the effect of anemia on mortality is mediated through intraoperative RBC transfusion.

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.

Intraoperative transfusion practices and perioperative outcome in the European elderly: A secondary analysis of the observational ETPOS study.

The demographic development suggests a dramatic growth in the number of elderly patients undergoing surgery in Europe. Most red blood cell transfusions (RBCT) are administered to older people, but little is known about perioperative transfusion practices in this population. In this secondary analysis of the prospective observational multicentre European Transfusion Practice and Outcome Study (ETPOS), we specifically evaluated intraoperative transfusion practices and the related outcomes of 3149 patients aged 65 years and older. Enrolled patients underwent elective surgery in 123 European hospitals, received at least one RBCT intraoperatively and were followed up for 30 days maximum. The mean haemoglobin value at the beginning of surgery was 108 (21) g/l, 84 (15) g/l before transfusion and 101 (16) g/l at the end of surgery. A median of 2 [1-2] units of RBCT were administered. Mostly, more than one transfusion trigger was present, with physiological triggers being preeminent. We revealed a descriptive association between each intraoperatively administered RBCT and mortality and discharge respectively, within the first 10 postoperative days but not thereafter. In our unadjusted model the hazard ratio (HR) for mortality was 1.11 (95% CI: 1.08-1.15) and the HR for discharge was 0.78 (95% CI: 0.74-0.83). After adjustment for several variables, such as age, preoperative haemoglobin and blood loss, the HR for mortality was 1.10 (95% CI: 1.05-1.15) and HR for discharge was 0.82 (95% CI: 0.78-0.87). Pre-operative anaemia in European elderly surgical patients is undertreated. Various triggers seem to support the decision for RBCT. A closer monitoring of elderly patients receiving intraoperative RBCT for the first 10 postoperative days might be justifiable. Further research on the causal relationship between RBCT and outcomes and on optimal transfusion strategies in the elderly population is warranted. A thorough analysis of different time periods within the first 30 postoperative days is recommended.

Effect of Perioperative Intravenous Iron Supplementation for Complex Cardiac Surgery on Transfusion Requirements: A Randomized, Double-blinded Placebo-controlled Trial.

OBJECTIVES: We investigated whether routine perioperative intravenous iron replenishment reduces the requirement for packed erythrocytes (pRBC) transfusion. SUMMARY OF BACKGROUND DATA: Patients undergoing complex cardiac surgery are at high risk of developing postoperative iron deficiency anemia, thus requiring transfusion, which is associated with adverse outcomes. METHODS: Patients were randomized to receive either ferric derisomaltose 20 mg/kg (n = 103) or placebo (n = 101) twice during the perioperative period: 3 days before and after the surgery. The primary endpoint was the proportion of patients who received pRBC transfusion until postoperative day (POD) 10. Hemoglobin, reticulocyte count, serum iron profile, hepcidin, and erythropoietin were serially measured. RESULTS: pRBC was transfused in 60.4% and 57.2% of patients in the control and iron group, respectively (P = 0.651). Hemoglobin concentration at 3 weeks postoperatively was higher in the iron group than in the control group (11.6 ± 1.5 g/dL vs 10.9 ± 1.4 g/dL, P < 0.001). The iron group showed higher reticulocyte count [205 (150-267)×103/µL vs 164 (122-207)×103/µL, P = 0.003] at POD 10. Transferrin saturation and serum ferritin were significantly increased in the iron group than in the control group (P < 0.001). Serum hepcidin was higher in the iron group than in the control group at POD 3 [106.3 (42.9-115.9) ng/mL vs 39.3 (33.3-43.6) ng/mL, P < 0.001]. Erythropoietin concentration increased postoperatively in both groups (P = 0.003), with no between-group difference. CONCLUSIONS: Intravenous iron supplementation during index hospitalization for complex cardiac surgery did not minimize pRBC transfusion despite replenished iron store and augmented erythropoiesis, which may be attributed to enhanced hepcidin expression.

Donor genetic and nongenetic factors affecting red blood cell transfusion effectiveness.

BACKGROUNDRBC transfusion effectiveness varies due to donor, component, and recipient factors. Prior studies identified characteristics associated with variation in hemoglobin increments following transfusion. We extended these observations, examining donor genetic and nongenetic factors affecting transfusion effectiveness.METHODSThis is a multicenter retrospective study of 46,705 patients and 102,043 evaluable RBC transfusions from 2013 to 2016 across 12 hospitals. Transfusion effectiveness was defined as hemoglobin, bilirubin, or creatinine increments following single RBC unit transfusion. Models incorporated a subset of donors with data on single nucleotide polymorphisms associated with osmotic and oxidative hemolysis in vitro. Mixed modeling accounting for repeated transfusion episodes identified predictors of transfusion effectiveness.RESULTSBlood donor (sex, Rh status, fingerstick hemoglobin, smoking), component (storage duration, γ irradiation, leukoreduction, apheresis collection, storage solution), and recipient (sex, BMI, race and ethnicity, age) characteristics were associated with hemoglobin and bilirubin, but not creatinine, increments following RBC transfusions. Increased storage duration was associated with increased bilirubin and decreased hemoglobin increments, suggestive of in vivo hemolysis following transfusion. Donor G6PD deficiency and polymorphisms in SEC14L4, HBA2, and MYO9B genes were associated with decreased hemoglobin increments. Donor G6PD deficiency and polymorphisms in SEC14L4 were associated with increased transfusion requirements in the subsequent 48 hours.CONCLUSIONDonor genetic and other factors, such as RBC storage duration, affect transfusion effectiveness as defined by decreased hemoglobin or increased bilirubin increments. Addressing these factors will provide a precision medicine approach to improve patient outcomes, particularly for chronically transfused RBC recipients, who would most benefit from more effective transfusion products.FUNDINGFunding was provided by HHSN 75N92019D00032, HHSN 75N92019D00034, 75N92019D00035, HHSN 75N92019D00036, and HHSN 75N92019D00037; R01HL126130; and the National Institute of Child Health and Human Development (NICHD).

Topical tranexamic acid in hip fractures: a randomized, placebo-controlled double-blinded study.

BACKGROUND: Tranexamic acid (TXA) has been shown to reduce perioperative blood loss in elective orthopedic surgery. The safety of intravenous TXA in nonelective hip fracture surgery is uncertain. The purpose of this study was to evaluate the efficacy and safety of topical TXA in hip fracture surgery. METHODS: Adult patients presenting to a community hospital with a hip fracture requiring surgery were randomly assigned to receive topical TXA or placebo. Hemoglobin and troponin I levels were measured preoperatively and on postoperative days 1, 2 and 3. All postoperative blood transfusions were recorded. Complications, including acute coronary syndrome (ACS), venous thromboembolism (VTE), cerebrovascular accidents (CVA), surgical site infections (SSI) and 90-day mortality, were recorded. RESULTS: Data were analyzed for 65 patients (31 in the TXA group, 34 in the control group). Hemogloblin level was significantly higher on postoperative days 1 and 2 in the TXA group than in the control group. The difference in hemoglobin level between the groups was not statistically significant by postoperative day 3. Significantly fewer units of packed red blood cells were transfused in the TXA group (2 units v. 8 units); however, 2 of the units in the control group were given intraoperatively, and when these were excluded the difference was not significant. The incidence of ACS, CVA, VTE, SSI, transfusion and all-cause mortality at 90 days did not differ significantly between the groups. CONCLUSION: Topical TXA reduces early postoperative blood loss after hip fracture surgery without increased patient risk. TRIAL REGISTRATION: Clinicaltrials.gov, no. NCT02993341.

Transfusion practices for pediatric oncology and hematopoietic stem cell transplantation patients: Data from the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III (REDS-III).

BACKGROUND: To evaluate transfusion practices in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients. STUDY DESIGN AND METHODS: This is a multicenter retrospective study of children with oncologic diagnoses treated from 2013 to 2016 at hospitals participating in the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III. Transfusion practices were evaluated by diagnosis codes and pre-transfusion laboratory values. RESULTS: A total of 4766 inpatient encounters of oncology and HSCT patients were evaluated, with 39.3% (95% confidence interval [CI]: 37.9%-40.7%) involving a transfusion. Red blood cells (RBCs) were the most commonly transfused component (32.4%; 95% CI: 31.1%-33.8%), followed by platelets (22.7%; 95% CI: 21.5%-23.9%). Patients in the 1 to <6 years of range were most likely to be transfused and HSCT, acute myeloid leukemia, and aplastic anemia were the diagnoses most often associated with transfusion. The median hemoglobin (Hb) prior to RBC transfusion was 7.5 g/dl (10-90th percentile: 6.4-8.8 g/dl), with 45.7% of transfusions being given at 7 to <8 g/dl. The median platelet count prior to platelet transfusion was 20 × 109 /L (10-90th percentile: 8-51 × 109 /L), and 37.9% of transfusions were given at platelet count of >20-50 × 109 /L. The median international normalized ratio (INR) prior to plasma transfusion was 1.7 (10-90th percentile: 1.3-2.7), and 36.3% of plasma transfusions were given at an INR between 1.4 and 1.7. DISCUSSION: Transfusion of blood components is common in hospitalized pediatric oncology/HSCT patients. Relatively high pre-transfusion Hb and platelet values and relatively low INR values prior to transfusion across the studied diagnoses highlight the need for additional studies in this population.

Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization: the PASTIME protocol.

BACKGROUND: Multidisciplinary care of placenta accreta spectrum cases improves pregnancy outcomes, but the specific components of such a multidisciplinary collaboration varies between institutions. As experience with placenta accreta spectrum increases, it is crucial to assess new surgical techniques and protocols to help improve maternal outcomes and to advocate for hospital resources. OBJECTIVE: This study aimed to assess a novel multidisciplinary protocol for the treatment of placenta accreta spectrum that comprises cesarean delivery, multivessel uterine embolization, and hysterectomy in a single procedure within a hybrid operative suite. STUDY DESIGN: This was a matched prepost study of placenta accreta spectrum cases managed before (2010-2017) and after implementation of the Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization protocol (2018-2021) at a tertiary medical center. Historical cases were managed with internal iliac artery balloon placement in selected cases with the decision to inflate the balloons intraoperatively at the discretion of the primary surgeon. Intraoperative Embolization cases were compared with historical cases in a 1:2 ratio matched on the basis of placenta accreta spectrum severity and surgical urgency. The primary outcome was a requirement for transfusion with packed red blood cells. Secondary outcomes included estimated surgical blood loss, operative and postoperative complications, procedural time, length of stay, and neonatal outcomes. RESULTS: A total of 15 Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization cases and 30 matched historical cases were included in the analysis. There were no demographic differences noted between the groups. A median (interquartile range) of 0 units (0-2 units) of packed red blood cells were transfused in the Intraoperative Embolization group compared with 2 units (0-4.5 units) in the historical group (P=.045); 5 of 15 (33.3%) Intraoperative Embolization cases required blood transfusions compared with 19 of 30 (63.3%) cases in the historical group (P=.11). The estimated blood loss was significantly less in the Intraoperative Embolization group with a median (interquartile range) of 750 mL (450-1050 mL) compared with 1750 mL (1050-2500 mL) in the historical group (P=.003). There were no cases requiring massive transfusion (≥10 red blood cell units in 24 hours) in the Intraoperative Embolization group compared with 5 of 30 (16.7%) cases in the historical group (P=.15). There were no intraoperative deaths from hemorrhagic shock using the Intraoperative Embolization protocol, whereas this occurred in 2 of the historical cases. The mean duration of the interventional radiology procedure was longer in the Intraoperative Embolization group (67.8 vs 34.1 minutes; P=.002). Intensive care unit admission and postpartum length of stay were similar, and surgical and postoperative complications were not significantly different between the groups. The gestational age and neonatal birthweights were similar; however, the neonatal length of stay was longer in the Intraoperative Embolization group (median duration, 32 days vs 15 days; P=.02) with a trend toward low Apgar scores. Incidence of arterial umbilical cord blood pH <7.2 and respiratory distress syndrome and intubation rates were not statistically different between the groups. CONCLUSION: A multidisciplinary pathway including a single-surgery protocol with multivessel uterine embolization is associated with a decrease in blood transfusion requirements and estimated blood loss with no increase in operative complications. The Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization protocol provides a definitive surgical method that warrants consideration by other centers specializing in placenta accreta spectrum treatment.

Platelet to erythrocyte transfusion ratio and mortality in massively transfused trauma patients. A systematic review and meta-analysis.

BACKGROUND: Platelet transfusion during major hemorrhage is important and often embedded in massive transfusion protocols. However, the optimal ratio of platelets to erythrocytes (platelet-rich plasma [PLT]/red blood cell [RBC] ratio) remains unclear. We hypothesized that high PLT/RBC ratios, as compared with low PLT/RBC ratios, are associated with improved survival in patients requiring massive transfusion. METHODS: Four databases (Pubmed, CINAHL, EMBASE, and Cochrane) were systematically screened for literatures published until January 21, 2021, to determine the effect of PLT/RBC ratio on the primary outcome measure mortality at 1 hour to 6 hours and 24 hours and at 28 days to 30 days. Studies comparing various PLT/RBC ratios were included in the meta-analysis. Secondary outcomes included intensive care unit length of stay and in-hospital length of stay and total blood component use. The study protocol was registered in PROSPERO under number CRD42020165648. RESULTS: The search identified a total of 8903 records. After removing the duplicates and second screening of title, abstract, and full text, a total of 59 articles were included in the analysis. Of these articles, 12 were included in the meta-analysis. Mortality at 1 hour to 6 hours, 24 hours, and 28 days to 30 days was significantly lower for high PLT/RBC ratios as compared with low PLT/RBC ratios. CONCLUSION: Higher PLT/RBC ratios are associated with significantly lower 1-hour to 6-hour, 24-hour, 28-day to 30-day mortalities as compared with lower PLT/RBC ratios. The optimal PLT/RBC ratio for massive transfusion in trauma patients is approximately 1:1. LEVEL OF EVIDENCE: Systematic review and meta-analysis, therapeutic Level III.

Association of perioperative red blood cell transfusions with all-cause and cancer-specific death in patients undergoing surgery for gastrointestinal cancer: Long-term outcomes from a population-based cohort.

BACKGROUND: Red blood cell transfusions are common in patients undergoing gastrointestinal cancer surgery. Yet, to adequately balance their risks and benefits, clinicians must understand how transfusions may affect long-term outcomes. We aimed to determine if perioperative red blood cell transfusions are associated with a higher risk of all-cause and cancer-specific death among patients who underwent gastrointestinal cancer resection. METHOD: We identified a population-based cohort of patients who underwent gastrointestinal cancer resection in Ontario, Canada (2007-2019). All-cause death was compared between transfused and nontransfused patients using Cox proportional hazards regression, while cancer-specific death was compared with competing risk regression. RESULT: A total of 74,962 patients (mean age, 67.7 years; 55.4% male; 79.7% colorectal cancer) had gastrointestinal cancer surgery during the study period; 20.8% received perioperative red blood cell transfusions. Patients who received red blood cell transfusions had increased hazards of all-cause and cancer-specific death relative to patients who did not (hazard ratio: 1.39, 95% confidence interval 1.34-1.44; cause-specific hazard ratio: 1.36, 1.30-1.43). The adjusted risk of all-cause death was higher in early follow-up intervals (3-6 months postoperatively) but remained elevated in each interval over 5 years. The association persisted after restricting to patients without postoperative complications or bleeding and was robust to unmeasured confounding. CONCLUSION: Red blood cell transfusion among patients with gastrointestinal cancer is associated with increased all-cause death. This was observed long beyond the immediate postoperative period and independent of short-term postoperative morbidity and mortality. These findings should help clinicians balance the risks and benefits of transfusion before well-designed trials are conducted in this patient population.

Predictors for blood loss and transfusion frequency to guide blood saving programs in primary knee- and hip-arthroplasty.

Endoprosthetic surgery can lead to relevant blood loss resulting in red blood cell (RBC) transfusions. This study aimed to identify risk factors for blood loss and RBC transfusion that enable the prediction of an individualized transfusion probability to guide preoperative RBC provision and blood saving programs. A retrospective analysis of patients who underwent primary hip or knee arthroplasty was performed. Risk factors for blood loss and transfusions were identified and transfusion probabilities computed. The number needed to treat (NNT) of a potential correction of preoperative anemia with iron substitution for the prevention of RBC transfusion was calculated. A total of 308 patients were included, of whom 12 (3.9%) received RBC transfusions. Factors influencing the maximum hemoglobin drop were the use of drain, tranexamic acid, duration of surgery, anticoagulation, BMI, ASA status and mechanical heart valves. In multivariate analysis, the use of a drain, low preoperative Hb and mechanical heart valves were predictors for RBC transfusions. The transfusion probability of patients with a hemoglobin of 9.0-10.0 g/dL, 10.0-11.0 g/dL, 11.0-12.0 g/dL and 12.0-13.0 g/dL was 100%, 33.3%, 10% and 5.6%, and the NNT 1.5, 4.3, 22.7 and 17.3, while it was 100%, 50%, 25% and 14.3% with a NNT of 2.0, 4.0, 9.3 and 7.0 in patients with a drain, respectively. Preoperative anemia and the insertion of drains are more predictive for RBC transfusions than the use of tranexamic acid. Based on this, a personalized transfusion probability can be computed, that may help to identify patients who could benefit from blood saving programs.

Predictors of Red Blood Cell Transfusion in Bimaxillary Orthognathic Surgery: A Retrospective Study.

Background: Orthognathic surgery requires red blood cell (RBC) transfusions more frequently than other oral and maxillofacial surgeries. The purpose of this study was to identify reliable predictors for RBC transfusion during bimaxillary orthognathic surgery (BOS). Methods: This retrospective study reviewed 1,616 electronic medical records of patients who underwent BOS during a 5-year period at Seoul National University Dental Hospital. The perioperative variable data were collected from electronic medical records and analyzed by dividing patients into the two groups (non-transfusion and transfusion group). Results: Of the 1,616 patients, 1,311 patients were excluded. The remaining 305 patients were divided into non-transfusion (NTF, n = 256) and transfusion (TF, n = 49) groups. Univariate logistic regression analysis revealed that age, body mass index, the presence of several adjunctive surgeries (including genioplasty, extraction, and mandibular angle reduction), preoperative hemoglobin (Hb) and prothrombin time, surgical time, amount of fluid infusion and blood loss, and mean pulse rate during surgery were significant factors predicting RBC transfusion. Multivariate logistic regression analysis revealed that preoperative Hb and blood loss amount during surgery were significantly related to RBC transfusion in BOS patients. Conclusion: Since blood loss amounts could not be measured preoperatively, we found that the independent predictor associated with RBC transfusion during BOS was a low preoperative Hb level.

Effectiveness of Preoperative Iron Supplementation in Major Surgical Patients With Iron Deficiency: A Prospective Observational Study.

OBJECTIVE: To evaluate the effectiveness of routine intravenous iron in surgical patients with iron deficiency anemia (IDA). BACKGROUND: Anemia is the most common medical disease in the world and is an independent risk factor for morbidity and mortality. Iron deficiency (ID) is the main cause for anemia and constitutes a potentially preventable condition with great impact on surgical outcome. METHODS: In this prospective single-center observational study, surgical patients were screened for the presence of anemia and ID. Patients were assigned to 1 of 4 study groups: A- (no anemia); A-, ID+, T+ (no anemia, iron-deficient, iron supplementation); A+ (anemia); and A+, ID+, T+ (anemia, iron-deficient, iron supplementation) according to hemoglobin level, iron status, and supplementation with iron. RESULTS: Among 1728 patients, 1028 were assigned to A-; 55 to A-, ID+, T+; 461 to A+; and 184 to A+, ID+, T+. While all iron-supplemented IDA patients required less red blood cell (RBC) transfusion during the postoperative period (A+ 42.5% vs A+, ID+, T+ 31.5%), a reduced intraoperative transfusion rate was observed for ID and IDA patients only if iron was supplemented >7 days before surgery. Hospital stay was significantly reduced by 2.8 days in iron-supplemented patients (P < 0.01 comparing 13.9 ±â€Š0.8 days for A+, ID+, T+ vs. 16.7 ±â€Š0.7 days for A+). CONCLUSION: Preoperative IDA management with intravenous iron is effective in improving hemoglobin level, thereby reducing intraoperative RBC transfusion rate particular if iron is administrated >7 days before surgery. Hospital length of stay was reduced in all preoperatively iron-supplemented IDA patients.

Impact of perioperative allogeneic blood transfusion on the long-term prognosis of patients with different stage tumors after radical resection for hepatocellular carcinoma.

BACKGROUND: We previously reported that perioperative allogeneic blood transfusion (PABT) did not affect long-term survival after radical resection for hepatocellular carcinoma (HCC). This study aimed to investigate the effects of PABT on the prognosis of HCC patients with different stage tumors. METHODS: Patients with primary HCC who underwent curative liver resection between 2003 and 2012 were retrospectively enrolled and divided into the early-stage (stage I) and non-early-stage (stages II, III and IV) groups. The impacts of PABT on the long-term prognosis of patients in different groups after resection were investigated using propensity score matching (PSM) and multivariable Cox regression analyses. RESULTS: We enrolled 426 HCC patients, including 53 matched pairs of patients with early-stage tumors and 51 matched pairs of patients with non-early-stage tumors. Survival analyses of the patients with early-stage tumors showed that the recurrence-free survival (RFS) and overall survival (OS) rates of the transfusion group were significantly worse than those of the nontransfusion group both before and after PSM. Multivariable Cox analyses identified that PABT was an independent predictor of RFS and OS of the patients with early-stage tumors. However, survival analyses of the propensity-matched patients with non-early-stage tumors showed no significant differences in RFS and OS rates between the transfusion and nontransfusion groups (p = 0.296; p = 0.472). CONCLUSIONS: This study demonstrates that PABT has negative impacts on the long-term prognosis of patients with early-stage tumors after radical resection of HCC but has no impact on the long-term prognosis of patients with non-early-stage tumors.

Imetelstat Achieves Meaningful and Durable Transfusion Independence in High Transfusion-Burden Patients With Lower-Risk Myelodysplastic Syndromes in a Phase II Study.

PURPOSE: Patients with lower-risk (LR) myelodysplastic syndromes (MDS) who are RBC transfusion dependent and have experienced relapse after or are refractory to erythropoiesis-stimulating agent (ESA) have limited treatment options. High telomerase activity and human telomerase reverse-transcription expression in clonal hematopoietic cells have been reported in patients with MDS. Imetelstat, a first-in-class competitive inhibitor of telomerase enzymatic activity, targets cells with active telomerase. We report efficacy, safety, and biomarker data for patients with LR MDS who are RBC transfusion dependent and who were relapsed/refractory to ESAs. PATIENTS AND METHODS: In this two-part phase II/III study (MDS3001), the primary end point was 8-week RBC transfusion independence (TI) rate, with key secondary end points of 24-week RBC TI rate, TI duration, and hematologic improvement-erythroid. RESULTS: Data from the phase II part of the study are reported. Of 57 patients enrolled and treated (overall population), 38 were non-del(5q) and hypomethylating agent and lenalidomide naïve (subset population). The 8- and 24-week RBC TI rates in the overall population were 37% and 23%, respectively, with a median TI duration of 65 weeks. In the subset population, 8- and 24-week RBC TI rates were 42% and 29%, respectively, with a median TI duration of 86 weeks. Eight-week TI rate was observed across all subgroups evaluated. Cytogenetic and mutational data revealed a reduction of the malignant clones, suggesting disease modification activity. The most common adverse events were cytopenias, typically reversible within 4 weeks. CONCLUSION: Imetelstat treatment results in a meaningful, durable TI rate across a broad range of heavily transfused patients with LR MDS who are ineligible for or relapsed/refractory to ESAs. Biomarker analyses indicated effects on the mutant malignant clone.

The incidence and effect of resternotomy following cardiac surgery on morbidity and mortality: a 1-year national audit on behalf of the Association of Cardiothoracic Anaesthesia and Critical Care.

Over 30,000 adult cardiac operations are carried out in the UK annually. A small number of these patients need to return to theatre in the first few days after the initial surgery, but the exact proportion is unknown. The majority of these resternotomies are for bleeding or cardiac tamponade. The Association of Cardiothoracic Anaesthesia and Critical Care carried out a 1-year national audit of resternotomy in 2018. Twenty-three of the 35 centres that were eligible participated. The overall resternotomy rate (95%CI) within the period of admission for the initial operation in these centres was 3.6% (3.37-3.85). The rate varied between centres from 0.69% to 7.6%. Of the 849 patients who required resternotomy, 127 subsequently died, giving a mortality rate (95%CI) of 15.0% (12.7-17.5). In patients who underwent resternotomy, the median (IQR [range]) length of stay on ICU was 5 (2-10 [0-335]) days, and time to tracheal extubation was 20 (12-48 [0-2880]) hours. A total of 89.3% of patients who underwent resternotomy were transfused red cells, with a median (IQR [range]) of 4 (2-7 [1-1144]) units of red blood cells. The rate (95%CI) of needing renal replacement therapy was 23.4% (20.6-26.5). This UK-wide audit has demonstrated that resternotomy after cardiac surgery is associated with prolonged intensive care stay, high rates of blood transfusion, renal replacement therapy and very high mortality. Further research into this area is required to try to improve patient care and outcomes in patients who require resternotomy in the first 24 h after cardiac surgery.