Abstract

BACKGROUND Time to treatment matters in traumatic haemorrhage but the optimal prehospital use of blood in major trauma remains uncertain. We investigated whether use of packed red blood cells (PRBC) and lyophilised plasma (LyoPlas) was superior to use of 0·9% sodium chloride for improving tissue perfusion and reducing mortality in trauma-related haemorrhagic shock. METHODS Resuscitation with pre-hospital blood products (RePHILL) is a multicentre, allocation concealed, open-label, parallel group, randomised, controlled, phase 3 trial done in four civilian prehospital critical care services in the UK. Adults (age ≥16 years) with trauma-related haemorrhagic shock and hypotension (defined as systolic blood pressure <90 mm Hg or absence of palpable radial pulse) were assessed for eligibility by prehospital critial care teams. Eligible participants were randomly assigned to receive either up to two units each of PRBC and LyoPlas or up to 1 L of 0·9% sodium chloride administered through the intravenous or intraosseous route. Sealed treatment packs which were identical in external appearance, containing PRBC-LyoPlas or 0·9% sodium chloride were prepared by blood banks and issued to participating sites according to a randomisation schedule prepared by the co-ordinating centre (1:1 ratio, stratified by site). The primary outcome was a composite of episode mortality or impaired lactate clearance, or both, measured in the intention-to-treat population. This study is completed and registered with ISRCTN.com, ISRCTN62326938. FINDINGS From Nov 29, 2016 to Jan 2, 2021, prehospital critical care teams randomly assigned 432 participants to PRBC-LyoPlas (n=209) or to 0·9% sodium chloride (n=223). Trial recruitment was stopped before it achieved the intended sample size of 490 participants due to disruption caused by the COVID-19 pandemic. The median follow-up was 9 days (IQR 1 to 34) for participants in the PRBC-LyoPlas group and 7 days (0 to 31) for people in the 0·9% sodium chloride group. Participants were mostly white (62%) and male (82%), had a median age of 38 years (IQR 26 to 58), and were mostly involved in a road traffic collision (62%) with severe injuries (median injury severity score 36, IQR 25 to 50). Before randomisation, participants had received on average 430 mL crystalloid fluids and tranexamic acid (90%). The composite primary outcome occurred in 128 (64%) of 199 participants randomly assigned to PRBC-LyoPlas and 136 (65%) of 210 randomly assigned to 0·9% sodium chloride (adjusted risk difference -0·025% [95% CI -9·0 to 9·0], p=0·996). The rates of transfusion-related complications in the first 24 h after ED arrival were similar across treatment groups (PRBC-LyoPlas 11 [7%] of 148 compared with 0·9% sodium chloride nine [7%] of 137, adjusted relative risk 1·05 [95% CI 0·46-2·42]). Serious adverse events included acute respiratory distress syndrome in nine (6%) of 142 patients in the PRBC-LyoPlas group and three (2%) of 130 in 0·9% sodium chloride group, and two other unexpected serious adverse events, one in the PRBC-LyoPlas (cerebral infarct) and one in the 0·9% sodium chloride group (abnormal liver function test). There were no treatment-related deaths. INTERPRETATION The trial did not show that prehospital PRBC-LyoPlas resuscitation was superior to 0·9% sodium chloride for adult patients with trauma related haemorrhagic shock. Further research is required to identify the characteristics of patients who might benefit from prehospital transfusion and to identify the optimal outcomes for transfusion trials in major trauma. The decision to commit to routine prehospital transfusion will require careful consideration by all stakeholders. FUNDING National Institute for Health Research Efficacy and Mechanism Evaluation.

Abstract

OBJECTIVES Transfusion with washed packed red blood cells (PRBCs) may be associated with reduced transfusion-related pro-inflammatory cytokine production. This may be because of alterations in recipient immune responses. METHODS This randomised trial evaluated the effect of transfusion with washed compared with unwashed PRBCs on pro-inflammatory cytokines and endothelial activation in 154 preterm newborns born before 29 weeks' gestation. Changes in plasma cytokines and measures of endothelial activation in recipient blood were analysed after each of the first three transfusions. RESULTS By the third transfusion, infants receiving unwashed blood had an increase in IL-17A (P = 0.04) and TNF (P = 0.007), whereas infants receiving washed blood had reductions in IL-17A (P = 0.013), TNF (P = 0.048), IL-6 (P = 0.001), IL-8 (P = 0.037), IL-12 (P = 0.001) and IFN-γ (P = 0.001). The magnitude of the post-transfusion increase in cytokines did not change between the first and third transfusions in the unwashed group but decreased in the washed group for IL-12 (P = 0.001), IL-17A (P = 0.01) and TNF (P = 0.03), with the difference between the groups reaching significance by the third transfusion (P < 0.001 for each cytokine). CONCLUSION The pro-inflammatory immune response to transfusion in preterm infants can be modified when PRBCs are washed prior to transfusion. Further studies are required to determine whether the use of washed PRBCs for neonatal transfusion translates into reduced morbidity and mortality.

Abstract

BACKGROUND Restrictive blood transfusion is recommended by major guidelines for perioperative management, but requires objective assessment at 7-10 g/dl haemoglobin (Hb). A scoring system that considers the physiological needs of the heart may simply the practice and reduce transfusion. METHODS Patients (14-65 years of age) undergoing non-cardiac surgery were randomised at a 1:1 ratio to a control group versus a Perioperative Transfusion Trigger Score (POTTS) group. POTTS (maximum of 10) was calculated as 6 plus the following: adrenaline infusion rate (0 for no infusion, 1 for ≤0.05 μg·kg(-1) ·min(-1) , and 2 for higher rate), FiO(2) to keep SpO(2) at ≥95% (0 for ≤35%, 1 for 36%-50%, and 2 for higher), core temperature (0 for <38°C, 1 for 38-40°C, and 2 for higher), and angina history (0 for no, 1 for exertional, and 2 for resting). Transfusion is indicated when actual Hb is lower than the calculated POTTS in individual patients. Transfusion in the control group was based on the 2012 American Association for Blood Banks (AABB) guideline. The primary outcome was the proportion of the patients requiring transfusion of allogeneic red blood cells (RBCs) during the perioperative period (until discharge from hospital), as assessed in the intention-to-treat (ITT) population (all randomised subjects). RESULT A total of 864 patients (mean age 44.4 years, 244 men and 620 women) were enrolled from December 2017 to January 2021 (433 in the control and 431 in the POTTS group). Baseline Hb was 9.2 ± 1.8 and 9.2 ± 1.7 g/dl in the control and POTTS groups, respectively. In the ITT analysis, the proportion of the patients receiving allogeneic RBCs was 43.9% (190/433) in the control group versus 36.9% (159/431) in the POTTS group (p = 0.036). Lower rate of allogeneic RBCs transfusion in the POTTS group was also evident in the per-protocol analysis (42.8% vs. 35.5%, p = 0.030). Transfusion volume was 4.0 (2.0, 6.0) and 3.5 (2.0, 5.5) units (200 ml/unit) in the control and POTTS groups, respectively (p = 0.25). The rate of severe postoperative complications (Clavien-Dindo grade IIIa and higher) was 3.9% in the control group versus 1.2% in the POTTS group (p = 0.010). CONCLUSION Transfusion of allogeneic RBCs based on the POTTS was safe and reduced the transfusion requirement in patients undergoing non-cardiac surgery.

Abstract

INTRODUCTION Around 5% of the world's population is expected to have some degree and type of thalassaemia. Beta thalassaemia (BT) occurs due to a deficient production of the beta-globin chain of haemoglobin. Extramedullary haematopoiesis (EMH) is one of the complications of BT, mainly observed in minor/intermedia subtypes. EMH is the production of blood cells outside the marrow as a compensatory response to longstanding hypoxia. Due to chronic transfusions, it is not expected in patients with beta-thalassaemia major (BTM). However, there are increasingly reported cases of EMH in BTM. The incidence of EMH in BTM is thought to be <1%. We aim to pool the available data and provide cumulative evidence on the occurrence of EMH in BTM patients. METHODS This is a systematic review of case reports, series, and retrospective studies that presented data on the occurrence of EMH in BTM patients. Data were recorded and analyzed in Microsoft Excel 2016 and SPSS 26. The protocol has been registered in PROSPERO CRD42021242943. RESULTS Data from 253 cases of EMH in BTM patients were extracted with a mean age of 35.3 years. Mean haemoglobin at presentation with EMH was 8.2 mg/dL. Lower limb weakness was the most common presenting feature (N = 23) (paraspinal EMH). Magnetic resonance imaging (MRI) was the most widely used diagnostic modality (226). Overall, blood transfusion was the commonest reported treatment (30), followed by radiotherapy (20), surgery (15), hydroxyurea (12), steroids (6), and exchange transfusion (2). An outcome was reported in 20% of patients, all recovered, except one who died as a result of nosocomial infection. CONCLUSION EMH is rare in BTM and can occur in any organ system with varied clinical features. MRI can effectively diagnose EMH, and conservative management has similar results compared to invasive treatments. Larger studies, focussing on outcomes may enhance guidelines on preventive and therapeutic strategies for managing EMH in BTM.KEY MESSAGESExtramedullary haematopoiesis is a rare complication in beta thalassaemia. Although it is more common in non-transfusion dependent thalassaemia, increasingly reported cases suggest a higher prevalence of EMH in TDT than what is known before.There are no clear guidelines on the management of EMH in TDT, with reported patients showing similar outcomes with conservative invasive treatment modalities.More extensive and preferably prospectively designed studies are required focussing on the management of EMH and its outcomes in patients with TDT to formulate evidence-based guidelines.

Abstract

AIM: To estimate the cost effectiveness and cost utility ratios of a restrictive vs liberal transfusion strategy in acute myocardial infarction (AMI) patients with anemia. METHODS AND RESULTS Patients (n = 666) with AMI and hemoglobin between 7-8 and 10 g/dL recruited in 35 hospitals in France and Spain were randomly assigned to a restrictive (n = 342) or a liberal (n = 324) transfusion strategy with 1-year prospective collection of resource utilization and quality of life using the EQ5D3L questionnaire. The economic evaluation was based upon 648 patients from the per-protocol population. The outcomes were 30-day and 1-year cost-effectiveness, with major adverse cardiovascular event averted (MACE) as the effectiveness outcome; and 1-year cost utility ratio.The 30-day incremental cost-effectiveness ratio was €33,065€ saved per additional MACE averted with the restrictive versus the liberal strategy, with an 84% probability for the restrictive strategy to be cost-saving and MACE reducing (i.e.dominant). At 1-year, the point estimate of the cost-utility ratio was 191,500 € saved per QALY gained; however cumulated MACE were outside the pre-specified non-inferiority margin, resulting in a decremental cost effectiveness ratio with a point estimate of €72,000 saved per additional MACE with the restrictive strategy. CONCLUSION In patients with acute myocardial infarction and anemia, the restrictive transfusion strategy was dominant (cost-saving and outcome-improving) at 30 days. At 1 year, the restrictive strategy remained cost-saving but clinical noninferiority on MACE was no longer maintained. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02648113.

Abstract

Secondary spontaneous pneumothorax (SSP) patients sometimes have a persistent air leak (PAL) that leads to increased morbidity and increased hospital stay. Further, these patients also need pleurodesis to prevent a recurrence. Autologous blood patch pleurodesis (ABPP) has been successfully tried in post lobectomy air leak cases. However, its utility in SSP patients with PAL has not been widely established. In this context, we performed a non-blinded randomized control study to compare the efficacy of ABPP vs doxycycline pleurodesis in the closure of air leak in SSP patients. This study was a non-blinded randomized control study done in 38 SSP patients with PAL. They were randomized into doxycycline arm and ABPP arm. Post pleurodesis air leak was assessed every 12 hours for cessation. Success was considered when there was a complete cessation of air leak. Post-procedural complications were noted and patients were followed up for 28 days to look for recurrence. The median time for closure was 24 hours [interquartile range (12.24)] for ABPP and 36 hours [interquartile range (24.72)] for doxycycline pleurodesis. Success rate of ABPP vs doxycycline pleurodesis is 94.7% vs 84.2% (p=0.6). Post-procedure pain was more in doxycycline group (15% vs 73%) (p<0.01). On visual analogue scale, ABPP had a lesser pain as compared to doxycycline pleurodesis (average visual analogue scale value of 2 vs scale of 7). The recurrence rate was equal in both groups (5%). Though ABPP and doxycycline have similar success rates, ABPP has an early closure of air leak and greater patient tolerability. ABPP can be tried as an alternative to doxycycline pleurodesis in SSP patients with persistent air leaks.

Abstract

BACKGROUND Anemia is a known risk factor for ischemic heart disease and serves as an independent predictor of major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS). This meta-analysis pools data from randomized controlled trials (RCTs) to better define hemoglobin (Hb) thresholds for transfusion in this setting. RESULTS MEDLINE, EMBASE, and Cochrane databases were searched using the terms "Acute Coronary Syndrome" AND "Blood Transfusion" including their synonyms. A total of three randomized controlled trials were included. Restrictive transfusion strategy (RTS) was defined as transfusing for Hb ≤ 8 g/dl with a post-transfusion goal of 8 to 10 g/dl. Liberal transfusion strategy (LTS) was defined as Hb ≤ 10 g/dl and post-transfusion goal of at least 11 g/dl. The primary end point was 30-day mortality. Secondary outcomes included recurrent ACS events, new or worsening CHF within 30 days, and major adverse cardiac events (MACE). The primary analytic method used was random effects model. Out of 821 patients, 400 were randomized to LTS, and 421 to RTS. Mean age was 70.3 years in RTS versus 76.4 in LTS. There was no statistically significant difference for 30-day mortality in LTS compared to RTS [odds ratio (OR) 1.69; 95% CI 0.35 to 8.05]. Similarly, there was no difference in MACE (OR 0.74; 95% CI 0.21 to 2.63), CHF (OR 0.82; 95% CI 0.18 to 3.76), or the incidence of recurrent ACS (OR 1.21; 95% CI 0.49 to 2.95). CONCLUSIONS In the setting of ACS, there is no difference between LTS and RTS for the outcomes of mortality, MACE, recurrent ACS, or CHF at 30 days. Further evidence in the form of high-quality RCTs are needed to compare RTS and LTS.

Abstract

Postpartum hemorrhage (PPH) is a major cause of maternal death and morbidity worldwide. Throughout the years, there have not been many studies looking into the association of race and ethnicity with the occurrence of PPH. The goal of this study was to assess race and ethnicity as risk factors in the development of PPH in pregnant women. Following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) standards, we conducted the analysis and conducted a literature search using Google Scholar and PubMed. After applying our inclusion and exclusion criteria, the search technique yielded a total of eight articles. The analysis included seven observational studies and one randomized controlled trial. The incidence of PPH was chosen as the major outcome measure. An evaluation of eight studies revealed that although Hispanics, Asians, Native Hawaiians, and other Pacific Islanders (NHOPI) have a higher chance of developing PPH caused by uterine atony, Caucasians had a greater rate of transfusion than the other groups. In addition, compared to Caucasians, African Americans or African descendants had a lower risk of atonic PPH but increased odds of atonic PPH requiring interventions. On the other hand, compared to non-native groups, Native Americans had increased odds of uterine atony. The results showed that, in contrast to other races/ethnicities, Caucasians had the lowest risk of PPH. Additionally, it was shown that African Americans or those descended from Africans had a higher chance of PPH but a lower risk of atonic PPH.

Abstract

OBJECTIVES Primary objective is to determine if transfusion of short storage RBCs compared with standard issue RBCs reduced risk of delirium/coma in critically ill children. Secondary objective is to assess if RBC transfusion was independently associated with delirium/coma. DESIGN This study was performed in two stages. First, we compared patients receiving either short storage or standard RBCs in a multi-institutional prospective randomized controlled trial. Then, we compared all transfused patients in the randomized controlled trial with a single-center cohort of nontransfused patients matched for confounders of delirium/coma. SETTING Twenty academic PICUs who participated in the Age of Transfused Blood in Critically Ill Children trial. PATIENTS Children 3 days to 16 years old who were transfused RBCs within the first 7 days of admission. INTERVENTIONS Subjects were randomized to either short storage RBC study arm (defined as RBCs stored for up to seven days) or standard issue RBC study arm. In addition, subjects were screened for delirium prior to transfusion and every 12 hours after transfusion for up to 3 days. MEASUREMENTS AND MAIN RESULTS Primary outcome measure was development of delirium/coma within 3 days of initial transfusion. Additional outcome measures were dose-response relationship between volume of RBCs transfused and delirium/coma, and comparison of delirium/coma rates between transfused patients and individually matched nontransfused patients. We included 146 subjects in the stage I analysis; 69 were randomized to short storage RBCs and 77 to standard issue. There was no significant difference in delirium/coma development between study arms (79.5% vs 70.1%; p = 0.184). In the stage II analysis, adjusted odds for delirium in the transfused cohort was more than eight-fold higher than in the nontransfused matched cohort, even after controlling for hemoglobin (adjusted odds ratio, 8.9; CI, 2.8-28.4; p < 0.001). CONCLUSIONS RBC transfusions (and not anemia) are independently associated with increased odds of subsequent delirium/coma. However, storage age of RBCs does not affect delirium risk.

Abstract

BACKGROUND The TRACT trial established the timing of transfusion in children with uncomplicated anaemia (haemoglobin 4-6 g/dL) and the optimal volume (20 vs 30 mL/kg whole blood or 10 vs 15 mL/kg red cell concentrates) for transfusion in children admitted to hospital with severe anaemia (haemoglobin <6 g/dL) on day 28 mortality (primary endpoint). Because data on the safety of blood components are scarce, we conducted a secondary analysis to examine the safety and efficacy of different pack types (whole blood vs red cell concentrates) on clinical outcomes. METHODS This study is a secondary analysis of the TRACT trial data restricted to those who received an immediate transfusion (using whole blood or red cell concentrates). TRACT was an open-label, multicentre, factorial, randomised trial conducted in three hospitals in Uganda (Soroti, Mbale, and Mulago) and one hospital in Malawi (Blantyre). The trial enrolled children aged between 2 months and 12 years admitted to hospital with severe anaemia (haemoglobin <6 g/dL). The pack type used (supplied by blood banks) was based only on availability at the time. The outcomes were haemoglobin recovery at 8 h and 180 days, requirement for retransfusion, length of hospital stay, changes in heart and respiratory rates until day 180, and the main clinical endpoints (mortality until day 28 and day 180, and readmission until day 180), measured using multivariate regression models. FINDINGS Between Sept 17, 2014, and May 15, 2017, 3199 children with severe anaemia were enrolled into the TRACT trial. 3188 children were considered in our secondary analysis. The median age was 37 months (IQR 18-64). Whole blood was the first pack provided for 1632 (41%) of 3992 transfusions. Haemoglobin recovery at 8 h was significantly lower in those who received packed cells or settled cells than those who received whole blood, with a mean of 1·4 g/dL (95% CI -1·6 to -1·1) in children who received 30 mL/kg and -1·3 g/dL (-1·5 to -1·0) in those who received 20 mL/kg packed cells versus whole blood, and -1·5 g/dL (-1·7 to -1·3) in those who received 30 mL/kg and -1·0 g/dL (-1·2 to -0·9) in those who received 20 mL/kg settled cells versus whole blood (overall p<0·0001). Compared to whole blood, children who received blood as packed or settled cells in their first transfusion had higher odds of receiving a second transfusion (odds ratio 2·32 [95% CI 1·30 to 4·12] for packed cells and 2·97 [2·18 to 4·05] for settled cells; p<0·001) and longer hospital stays (hazard ratio 0·94 [95% CI 0·81 to 1·10] for packed cells and 0·86 [0·79 to 0·94] for settled cells; p=0·0024). There was no association between the type of blood supplied for the first transfusion and mortality at 28 days or 180 days, or readmission to hospital for any cause. 823 (26%) of 3188 children presented with severe tachycardia and 2077 (65%) with tachypnoea, but these complications resolved over time. No child developed features of confirmed cardiopulmonary overload. INTERPRETATION Our study suggests that the use of packed or settled cells rather than whole blood leads to additional transfusions, increasing the use of a scarce resource in most of sub-Saharan Africa. These findings have substantial cost implications for blood transfusion and health services. Nevertheless, a clinical trial comparing whole blood transfusion with red cell concentrates might be needed to inform policy makers. FUNDING UK Medical Research Council (MRC) and the Department for International Development. TRANSLATION For the French translation of the abstract see Supplementary Materials section.