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Orthopaedic Trauma and Anemia: Conservative versus Liberal Transfusion Strategy: A Prospective Randomized Study
Mullis, B. H., Mullis, L. S., Kempton, L. B., Virkus, W., Slaven, J. E., Bruggers, J.
Journal of orthopaedic trauma. 2024;38(1):18-24
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Editor's Choice
Abstract
OBJECTIVES To determine whether it is safe to use a conservative packed red blood cell transfusion hemoglobin (Hgb) threshold (5.5 g/dL) compared with a liberal transfusion threshold (7.0 g/dL) for asymptomatic musculoskeletal injured trauma patients who are no longer in the initial resuscitative period. METHODS Design: Prospective, randomized, multicenter trial. SETTING Three level 1 trauma centers. PATIENT SELECTION CRITERIA Patients aged 18-50 with an associated musculoskeletal injury with Hgb less than 9 g/dL or expected drop below 9 g/dL with planned surgery who were stable and no longer being actively resuscitated were randomized once their Hgb dropped below 7 g/dL to a conservative transfusion threshold of 5.5 g/dL versus a liberal threshold of 7.0 g/dL. OUTCOME MEASURES AND COMPARISONS Postoperative infection, other post-operative complications and Musculoskeletal Functional Assessment scores obtained at baseline, 6 months, and 1 year were compared for liberal and conservative transfusion thresholds. RESULTS Sixty-five patients completed 1 year follow-up. There was a significant association between a liberal transfusion strategy and higher rate of infection (P = 0.01), with no difference in functional outcomes at 6 months or 1 year. This study was adequately powered at 92% to detect a difference in superficial infection (7% for liberal group, 0% for conservative, P < 0.01) but underpowered to detect a difference for deep infection (14% for liberal group, 6% for conservative group, P = 0.2). CONCLUSIONS A conservative transfusion threshold of 5.5 g/dL in an asymptomatic young trauma patient with associated musculoskeletal injuries leads to a lower infection rate without an increase in adverse outcomes and no difference in functional outcomes at 6 months or 1 year. LEVEL OF EVIDENCE Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
PICO Summary
Population
Musculoskeletal trauma patients with planned surgery (n= 99).
Intervention
Liberal transfusion threshold of 7.0 g/dL (n= 49).
Comparison
Conservative transfusion threshold of 5.5 g/dL (n= 50).
Outcome
Overall, 46/49 (93.9%) of the liberal group had a transfusion versus 23/50 (46.0%) of the conservative group had a transfusion after resuscitation and after enrollment in this study. Following resuscitation and enrollment in the study, patients in the liberal group received a median of 1 unit of blood transfused (range 0–12) and patients in the conservative group received a median of 0 units of blood (range 0–14). Sixty-five patients completed 1- year follow-up. There was a significant association between a liberal transfusion strategy and higher rate of infection, with no difference in functional outcomes at 6 months or 1 year.
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Red cell transfusion thresholds in outpatients with myelodysplastic syndromes: Results of a pilot randomized trial RBC-ENHANCE
Buckstein, R., Callum, J., Prica, A., Bowen, D., Wells, R. A., Leber, B., Heddle, N., Chodirker, L., Cheung, M., Mozessohn, L., et al
Transfusion. 2024
Abstract
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.
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The role of preoperative transfusion in sickle cell disease, a systematic review and meta-analysis
Abdu, Y., Rahhal, A., Ahmed, K., Adli, N., Abdou, M., Ali, E. A. H., Al-Kindi, S., Al Rasheed, M., Altooq, J., Bougmiza, I., et al
Blood reviews. 2024;:101183
Abstract
This systematic review and meta-analysis aimed to provide guidance on preoperative blood transfusion strategies for patients with sickle cell disease (SCD). We included all randomized controlled and observational studies exploring the clinical outcomes of preoperative blood transfusion among patients with SCD compared to the conservative transfusion strategy until 14/09/2022. Sixteen studies involving 3486 participants were analysed. The findings revealed a significantly higher bleeding rate in patients who received preoperative transfusion than those who followed a conservative strategy (RR = 4.32, 95% CI 1.75-10.68, P = 0.002, I2 = 0%). However, the two strategies had no significant differences in other clinical outcomes, such as acute chest syndrome, painful crisis, fever, neurological complications, thrombosis, ICU admission, and mortality. It is important to note that all the included studies had a moderate risk of bias. Preoperative transfusion in SCD was associated with a higher bleeding risk but a similar risk in other outcomes compared to conservative strategies. Notably, the increased bleeding risk observed seldom had clinical significance. We recommend individualizing management strategies, considering the overall positive impact of transfusions in reducing complications. Further high-quality studies are needed to refine recommendations.
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Early Results of Orthopaedic Trauma and Anemia: Conservative Versus Liberal Transfusion Strategy
Mullis, B. H., Mullis, L. S., Kempton, L. B., Virkus, W., Slaven, J. E., Bruggers, J.
The Journal of the American Academy of Orthopaedic Surgeons. 2023
Abstract
INTRODUCTION The purpose of this study was to determine whether it is safe to use a conservative packed red blood cell transfusion hemoglobin threshold (5.5 g/dL) compared with a liberal transfusion threshold (7.0 g/dL) for asymptomatic patients with musculoskeletal-injured trauma out of the initial resuscitative period. METHODS This was a multicenter, prospective, nonblinded, randomized study done at three level 1 trauma centers. One hundred patients were enrolled. One patient was inappropriately enrolled, withdrawn from the study, and excluded from analysis leaving 99 patients (49 liberal and 50 conservative) with 30-day follow-up. After initial resuscitation, patients were enrolled and randomized to either a liberal or a conservative transfusion strategy. This strategy was followed throughout the index hospitalization. The primary outcome of the study was infection. Superficial infection was defined as clinical diagnosis of cellulitis or other superficial infection treated with oral antibiotics only. Deep infection was defined as clinical diagnosis of fracture-related infection requiring IV antibiotics and/or surgical débridement. RESULTS Ninety-nine patients were successfully followed for 30 days with 100% follow-up during this time. Seven infections (14%) occurred in the liberal group and none in the conservative group (P < 0.01). Five deep infections (10%) occurred in the liberal group and none in the conservative group (P = 0.03). Three superficial infections (6%) occurred in the liberal and none in the conservative group, which was not a significant difference (P = 0.1). No difference was observed in length of stay between groups. DISCUSSION Transfusing young healthy asymptomatic patients with orthopaedic trauma for hemoglobin <7.0 g/dL increases the risk of infection. No increased risk of anemia-related complications was identified with a conservative transfusion threshold of 5.5 g/dL. DATA AVAILABILITY AND TRIAL REGISTRATION NUMBERS Data are available on request. IRB protocol number is 1402557771. This study was registered with Clinicaltrials.gov identifier NCT02972593. LEVEL OF EVIDENCE Level 2, unblinded prospective randomized multicenter study.
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Association of Trauma Molecular Endotypes With Differential Response to Transfusion Resuscitation Strategies
Thau MR, Liu T, Sathe NA, O'Keefe GE, Robinson BRH, Bulger E, Wade CE, Fox EE, Holcomb JB, Liles WC, et al
JAMA surgery. 2023
Abstract
IMPORTANCE It is not clear which severely injured patients with hemorrhagic shock may benefit most from a 1:1:1 vs 1:1:2 (plasma:platelets:red blood cells) resuscitation strategy. Identification of trauma molecular endotypes may reveal subgroups of patients with differential treatment response to various resuscitation strategies. OBJECTIVE To derive trauma endotypes (TEs) from molecular data and determine whether these endotypes are associated with mortality and differential treatment response to 1:1:1 vs 1:1:2 resuscitation strategies. DESIGN, SETTING, AND PARTICIPANTS This was a secondary analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) randomized clinical trial. The study cohort included individuals with severe injury from 12 North American trauma centers. The cohort was taken from the participants in the PROPPR trial who had complete plasma biomarker data available. Study data were analyzed on August 2, 2021, to October 25, 2022. EXPOSURES TEs identified by K-means clustering of plasma biomarkers collected at hospital arrival. MAIN OUTCOMES AND MEASURES An association between TEs and 30-day mortality was tested using multivariable relative risk (RR) regression adjusting for age, sex, trauma center, mechanism of injury, and injury severity score (ISS). Differential treatment response to transfusion strategy was assessed using an RR regression model for 30-day mortality by incorporating an interaction term for the product of endotype and treatment group adjusting for age, sex, trauma center, mechanism of injury, and ISS. RESULTS A total of 478 participants (median [IQR] age, 34.5 [25-51] years; 384 male [80%]) of the 680 participants in the PROPPR trial were included in this study analysis. A 2-class model that had optimal performance in K-means clustering was found. TE-1 (n = 270) was characterized by higher plasma concentrations of inflammatory biomarkers (eg, interleukin 8 and tumor necrosis factor α) and significantly higher 30-day mortality compared with TE-2 (n = 208). There was a significant interaction between treatment arm and TE for 30-day mortality. Mortality in TE-1 was 28.6% with 1:1:2 treatment vs 32.6% with 1:1:1 treatment, whereas mortality in TE-2 was 24.5% with 1:1:2 treatment vs 7.3% with 1:1:1 treatment (P for interaction = .001). CONCLUSIONS AND RELEVANCE Results of this secondary analysis suggest that endotypes derived from plasma biomarkers in trauma patients at hospital arrival were associated with a differential response to 1:1:1 vs 1:1:2 resuscitation strategies in trauma patients with severe injury. These findings support the concept of molecular heterogeneity in critically ill trauma populations and have implications for tailoring therapy for patients at high risk for adverse outcomes.
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Preoperative Transfusion in Sickle Cell Disease Children Undergoing Adenotonsillectomy
Kanotra, S., Muller, S. H., Kanotra, J., Gardner, R., Kanotra, S. P.
Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India. 2023;75(2):227-235
Abstract
OBJECTIVE To perform a systematic review and meta-analysis comparing two pre-operative transfusion regimens (conservative versus aggressive) in children with sickle cell disease(SCD) undergoing adenotonsillectomy in terms of post-operative complications, complications related to SCD and transfusion related complications. DATA SOURCES AND REVIEW METHODS A literature review was performed through PubMed, EMBASE, Cochrane, and Ovid databases using the following phrases: (Adenotonsillectomy OR Tonsillectomy) AND (Sickle Cell Disease OR Sickle Cell Trait). Using predetermined inclusion and exclusion criteria, seven articles were selected for systemic review and two control trials were included in meta-analysis. RESULTS Out of a total of 3,146 results, seven articles were selected for review and two controlled trials were included in the meta-analysis. There was no statistically significant difference in the rate of primary and secondary hemorrhage between the aggressive and conservative transfusion regimens (RR = 3.1, CI = 0.84-11.4, p-value = 0.089). The rate of sickle cell disease related complications including vaso-occlusive crisis and acute chest syndrome was also not statistically significant between the two transfusion groups (RR = 1.4, CI = 0.7-2.8, p-value = 0.339). Even though, the transfusion related complications did not reach statistical significance, there was a higher complication rate in the group receiving aggressive blood transfusion. CONCLUSION In SCD children undergoing adenotonsillectomy, an aggressive transfusion regimen that focuses on reducing the Hemoglobin S ratio to below 30% has not been shown to be more effective in reducing post-operative complications when compared to a conservative transfusion regimen. Therefore, it is reasonable to utilize a conservative transfusion regimen, thereby reducing the transfusion-associated risks.
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Evidence-based interventions for reducing sickle cell disease-associated morbidity and mortality in sub-Saharan Africa: A scoping review
Arji, E. E., Eze, U. J., Ezenwaka, G. O., Kennedy, N.
SAGE open medicine. 2023;11:20503121231197866
Abstract
OBJECTIVE Sickle cell disease is a lifelong illness affecting millions of people globally, but predominantly burdensome in sub-Saharan Africa, where most affected children do not live to adulthood, despite available evidence-based interventions that reduce the disease burden in high-income countries. METHOD We reviewed studies evaluating evidence-based interventions that decrease sickle cell disease-related morbidity and mortality among children living in sub-Saharan Africa. We used the Joanna Briggs scoping review methodological framework and grouped identified evidence-based interventions into preventative pharmacotherapeutic agents, newborn screening and comprehensive healthcare, disease-modifying agents, nutritional supplementation, systemic treatment, supportive agents and patient/carer/population education. RESULTS We included 36 studies: 18 randomized controlled trials, 11 observational studies, 5 before-and-after studies and 2 economic evaluation studies, with most of the studies performed in West African countries. Included studies suggest evidence-based interventions effectively to reduce the common morbidities associated with sickle cell disease such as stroke, vaso-occlusive crisis, acute chest syndrome, severe anaemia and malaria infection. Evidence-based interventions also improve survival among study participants. Specifically, our review shows hydroxyurea increases haemoglobin and foetal haemoglobin levels, a finding with practical implications given the challenges with blood transfusion in this setting. The feasibility of implementing individual interventions is hampered by challenges such as affordability, accessibility and the availability of financial and human resources. CONCLUSION Our review suggests that regular use of low-dose hydroxyurea therapy, sulphadoxine-pyrimethamine chemoprophylaxis, L-arginine and Omega-3 fatty acid supplementation and establishment of specialist stand-alone sickle cell clinics could reduce the sickle cell disease-associated morbidity and mortality in sub-Saharan Africa countries.
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Preoperative hemoglobin and perioperative blood transfusion in major head and neck surgery: a systematic review and meta-analysis
Ali, M., Dort, J. C., Sauro, K. M.
Journal of Otolaryngology - Head & Neck Surgery = Le Journal D'oto-Rhino-Laryngologie Et De Chirurgie Cervico-Faciale. 2023;52(1):3
Abstract
BACKGROUND There is a growing concern with inappropriate, excessive perioperative blood transfusions. Understanding the influence of low preoperative hemoglobin (Hgb) on perioperative blood transfusion (PBT) in head and neck cancer (HNC) surgery with free flap reconstruction may help guide clinical practice to reduce inappropriate treatment among these patients. The objective is to synthesize evidence regarding the association between preoperative Hgb and PBT among major HNC free flap surgeries. METHODS Terms and synonyms for HNC surgical procedures, Hgb and PBT were used to search MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials and Cochrane Database of Reviews from inception to February 2020. Reference lists of included full texts and studies reporting the preoperative Hgb, anemia or hematocrit (exposure) and the PBT (outcome) in major HNC surgery with free flap reconstruction were eligible. Studies examining esophageal, thyroid and parathyroid neoplasms were excluded; as were case reports, case series (n < 20), editorials, reviews, perspectives, viewpoints and responses. Two independent, blinded reviewers screened titles, abstracts and full texts in duplicate. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses was followed. A random-effects model was used to pool reported data. The primary outcome was the proportion of patients who had a PBT. Subgroup analysis examined sources of heterogeneity for perioperative predictors of PBT (age, sex, flap type, flap site and preoperative Hgb). We also examined mean preoperative Hgb in the PBT and no PBT groups. RESULTS Patients with low preoperative Hgb were transfused more than those with normal Hgb (47.62%, 95% CI = 41.19-54.06, I(2) = 0.00% and 13.92%, 95% CI = 10.19-17.65, I(2) = 20.69%, respectively). None of the predictor variables explained PBT. The overall pooled mean preoperative Hgb was 12.96 g/dL (95% CI = 11.33-14.59, I(2) = 0.00%) and was 13.58 g/dL (95% CI = 11.95-15.21, I(2) = 0.00%) in the no PBT group and 12.05 g/dL (95% CI = 10.01 to 14.09, I(2) = 0.00%) in the PBT group. CONCLUSIONS The heterogeneity between studies, especially around the trigger for PBT, highlights the need for additional research to guide clinical practice of preoperative Hgb related to PBT to enhance patient outcomes and improve healthcare stewardship.
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Frequency of red blood cell transfusions in preterm neonates in Brazil: A systematic review and meta-analysis
Valete, C. O. S., Angelica Luiz Ferreira, E., Montenegro, C. P., Pilati, M. C. A., Rodrigues Wilde, M. O. D., Witkowski, S. M.
Vox sanguinis. 2023
Abstract
BACKGROUND AND OBJECTIVES Red blood cell transfusions are frequent in preterm neonates. The proportion of preterm neonates transfused in Brazil remains unknown. We systematically reviewed the literature to estimate the frequency of red blood cell transfusions in preterm neonates in Brazil. MATERIALS AND METHODS The LILACS, EMBASE, Cochrane, SciELO, MEDLINE (PubMed), Web of Science, Scopus, BDTD and 27 national university institutional databases were searched for studies that analysed red blood cell transfusion in preterm neonates in Brazil without period restriction. The Preferred Reporting Items in Systematic Reviews and Meta-Analyses guidelines were followed, and the GRADE methodology was applied. A random-effects model along with the restricted maximum likelihood method was used, and the Freeman-Tukey transformed proportion was used to estimate effect size. RESULTS Nine studies, representing 6548 preterm neonates, were included in the qualitative and quantitative analyses. The mean gestational age ranged from 26.0 to 31.6 weeks. Most of the studies were from the Southeast region. The pooled estimated frequency of red blood cell transfusions was 58.0% (95% confidence interval = 52.0%-64.0%, p < 0.001) with low certainty. There was statistically significant heterogeneity among studies (I(2) = 92.5%, p < 0.001). CONCLUSION In this current meta-analysis of the evidence available, which included moderate and extremely preterm neonates, the observed frequency of red blood cell transfusions in preterm neonates in Brazil was 58.0% and this estimate can help health programming. Some Brazilian regions were not included in this study, and further research is needed to provide a more representative overview of Brazil.
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10.
Pegcetacoplan controls hemolysis in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria
Wong RSM, Navarro-Cabrera JR, Comia NS, Goh YT, Idrobo H, Kongkabpan D, Gómez-Almaguer D, Al-Adhami M, Ajayi T, Alvarenga P, et al
Blood advances. 2023
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Editor's Choice
Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease characterized by complement-mediated hemolysis. Pegcetacoplan is the first C3-targeted therapy approved for adults with PNH (United States), adults with PNH with inadequate response to or intolerance of a C5 inhibitor (Australia), and adults with anemia despite C5-targeted therapy for 3 months (European Union). PRINCE was a phase 3, randomized, multicenter, open-label, controlled study to evaluate efficacy and safety of pegcetacoplan versus control (supportive care only; eg, blood transfusions, corticosteroids, and supplements) in complement inhibitor-naive patients with PNH. Eligible adults receiving supportive care only for PNH were randomized and stratified based on their number of transfusions (<4, ≥4) 12 months before screening. Patients received pegcetacoplan 1080 mg subcutaneously twice weekly or continued supportive care (control) for 26 weeks. Coprimary endpoints were hemoglobin stabilization (avoidance of >1-g/dL decrease in hemoglobin levels without transfusions) from baseline through week 26 and lactate dehydrogenase (LDH) change at week 26. Overall, 53 patients received pegcetacoplan (n=35) or control (n=18). Pegcetacoplan was superior to control for hemoglobin stabilization (pegcetacoplan, 85.7%; control, 0; difference, 73.1% [95% CI: 57.2, 89.0]; P <0.0001) and change from baseline in LDH (least-square mean change: pegcetacoplan, -1870.5 U/L; control -400.1 U/L; difference, -1470.4 U/L [95% CI: -2113.4, -827.3]; P <0.0001). Pegcetacoplan was well tolerated. No pegcetacoplan-related adverse events were serious, and no new safety signals observed. Pegcetacoplan rapidly and significantly stabilized hemoglobin and reduced LDH in complement inhibitor-naive patients and had a favorable safety profile. This trial was registered at www.clinicaltrials.gov as #NCT04085601.
PICO Summary
Population
Adult patients with paroxysmal nocturnal haemoglobinuria enrolled in the PRINCE trial conducted in 22 centres in Hong Kong, Malaysia, Philippines, Singapore, Thailand, Colombia, Mexico and Peru (n= 53).
Intervention
Subcutaneous infusions of pegcetacoplan (pegcetacoplan group, n= 35).
Comparison
Supportive care including transfusions, anticoagulants, corticosteroids, and supplements (control group, n= 18).
Outcome
Pegcetacoplan was superior to control for haemoglobin stabilization (pegcetacoplan, 85.7%; control, 0; difference, 73.1%, 95% CI [57.2, 89.0]) and change from baseline in lactate dehydrogenase, (least-square mean change: pegcetacoplan, -1870.5 U/L; control -400.1 U/L; difference, -1470.4 U/L, 95% CI [-2113.4, -827.3]). Pegcetacoplan was well tolerated. No pegcetacoplan-related adverse events were serious, and no new safety signals were observed.