Abstract

BACKGROUND Whole blood (WB) transfusion received renewed interest after recent armed conflicts. The effectiveness as compared to blood component transfusion (BCT) is however still topic of debate. Therefore, this study investigated the effect of WB ± BCT as compared to BCT transfusion on survival in trauma patients with acute hemorrhage. METHODS Studies published up to the 16th of January 2023, including patients with traumatic hemorrhage comparing WB ± BCT and BCT were included in meta-analysis. Sub analyses were performed on the effectiveness of WB in the treatment of civilian or military trauma patients, patients with massive hemorrhage and on platelet (PLT):Red Blood Cell (RBC), plasma:RBC and WB:RBC ratios. Methodological quality of studies was interpreted using the Cochrane risk of bias tool. The study protocol was registered in PROSPERO under number CRD42022296900. RESULTS Random effect pooled odds ratio (OR) for 24-hours mortality in civilian and military patients treated with WB as compared to BCT was 0.72 (95% CI 0.53-0.97). In sub analysis of studies conducted in civilian setting (n = 20), early (4-hours, 6-hours and Emergency Department) and 24-hours mortality was lower in WB groups compared BCT groups: OR 0.65 (95% CI 0.44 - 0.96) and OR 0.71 (0.52 - 0.98). No difference in late mortality (28-days, 30-days, in-hospital) was found. In military settings (n = 7) there was no difference in early, 24-hours or late mortality between groups. WB groups received significant higher PLT:RBC (p = 0.030) during early treatment and significant higher PLT:RBC and Plasma:RBC ratios during 24-hours of treatment (p = 0.031 and p = 0.007). The overall risk of bias in the majority of studies was judged as serious due to serious risk on confounding and selection bias, and unclear information regarding co-interventions. CONCLUSION Civilian trauma patients with acute traumatic hemorrhage treated with WB ± BCT as compared to BCT had lower odds on early and 24-hours mortality. Additionally, WB transfusion resulted in higher plt:RBC and plasma:RBC ratios. LEVEL OF EVIDENCE Level III, systematic review and meta-analysis.

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.

Abstract

INTRODUCTION Low titer group O whole blood (LTOWB) resuscitation is increasingly common in both military and civilian settings. Data regarding the safety and efficacy of prehospital LTOWB remains limited. METHODS We performed a single center, prospective, cluster randomized, prehospital thru in-hospital whole blood pilot trial for injured air medical patients. We compared standard prehospital air medical care including red cell transfusion and crystalloids followed by in-hospital component transfusion to prehospital and in-hospital LTOWB resuscitation. Prehospital vital signs were used as inclusion criteria (SBP ≤ 90 mmHg and HR ≥ 108 bpm) or (SBP ≤ 70 mmHg) for patients at risk of hemorrhage. Primary outcome was feasibility. Secondary outcomes included 28-day and 24 hour mortality, multiple organ failure, nosocomial infection, 24 hr transfusion requirements and arrival coagulation parameters. RESULTS Between November 2018 thru October 2020, 86 injured patients were cluster randomized by helicopter base. The trial has halted early at 77% enrollment. Overall, 28-day mortality for the cohort was 26%. Injured patients randomized to prehospital LTOWB (n = 40) relative to standard care (n = 46) were similar in demographics and injury characteristics. Intent to treat Kaplan-Meier survival analysis demonstrated no statistical mortality benefit at 28 days (25.0% vs. 26.1%, p = 0.85). Patients randomized to prehospital LTOWB relative to standard care had lower red cell transfusion requirements at 24 hours (p < 0.01) and a lower incidence of abnormal thromboelastographic measurements. No transfusion reactions during the prehospital or in-hospital phase of care were documented. CONCLUSION Prehospital through in-hospital LTOWB resuscitation is safe and may be associated with hemostatic benefits. A large-scale clinical trial is feasible with protocol adjustment and would allow the effects of prehospital LTOWB on survival and other pertinent clinical outcomes to be appropriately characterized. LEVEL OF EVIDENCE II, Cluster randomized pilot trial.

Abstract

Our aim was to assess whether there is a difference in outcomes of potential "all-cause" harm in the transfusion of whole blood (WB) compared to blood components (BC) for any bleeding patient regardless of age or clinical condition. We searched multiple electronic databases using a pre-defined search strategy from inception to 2(nd) March 2021. 1 reviewer screened, extracted, and analysed data, with verification by a second reviewer of all decisions. We used Cochrane ROB1 and GRADE to assess the quality of the evidence. We used predefined subgroups of trauma and non-trauma studies in the analysis. We included six RCTs (618 participants) which compared WB and BC transfusion therapy in major bleeding, one trauma trial (n = 107), and 5 surgical trials (non-trauma) (n = 511). We GRADED evidence as very-low for all outcomes (downgraded for high and unclear risk of bias, small sample size, and wide confidence intervals around the estimate). Our primary outcome (all-cause mortality at 24-hours and 30-days) was reported in 3 out of 6 included trials. There was no evidence of a difference in mortality of WB compared to BC therapy (very-low certainty evidence). There may be a benefit of WB therapy compared to BC therapy in the non-trauma subgroup, with a reduction in the duration of oxygen dependence (1 study; n = 60; mean difference 5.9 fewer hours [95% Confidence Interval [CI] -10.83, -0.99] in WB group), and a reduction in hospital stay (1 study, n = 64, median difference 6 fewer days in WB group) (very-low certainty evidence). For the remaining outcomes (organ injury, mechanical ventilation and intensive care unit requirement, infection, arterial/venous thrombotic events, and haemolytic transfusion reaction) there was no difference between WB and BC therapy (wide CI, crossing line of no effect), though many of these outcomes were based on small single studies (very-low certainty evidence). In conclusion, there appears to be little to no difference in harms between WB and BC therapy, based on small studies with very low certainty of the evidence. Further large trials are required to establish the overall safety of WB compared to BC, and to assess differences between trauma and non-trauma patients.

Abstract

BACKGROUND The major causes of death of combat casualties in austere environments are related to hemorrhage and occur early after injury. The implementation of a walking blood bank may overcome the logistical issues raised using blood component therapy. Nonetheless, it is important to ensure that this buddy transfusion is not going to compromise the mission success by altering the donor's performance. The results available so far cannot rule out this issue with certainty. Therefore, this study aimed at investigating the immediate effect of a 450-ml blood donation on the performances of elite soldiers in laboratory and field environments. STUDY DESIGN AND METHODS This double-blind, randomized controlled study included two experiments. For both experiments, subjects were randomly assigned either to a control group (n(1) = n(2) = 7) or to a 450-ml-blood-bag donation group (n(1) = 7 and n(2) = 8). All participants underwent before and after a potential blood donation a multifactorial assessment including adapted physical tasks, hematological variables, vigilance parameters, and subjective assessments. RESULTS No significant results were evidenced in this study. There was no impact of blood donation on the participants' performances in both the hospital and the combat-like environments. CONCLUSION From a donor's point of view, a 450-ml blood donation has no impact on the required abilities of our elite soldiers to fulfill a demanding tactical mission. Thus, the results of this study support the fact that buddy transfusions could be part of the operational clinical armamentarium in austere environments for elite soldiers when no blood components are available.

Abstract

INTRODUCTION Hemorrhage is a leading cause of death among trauma patients, and is the most common cause of preventable death after trauma. Since the advent of blood component fractioning, most patients receive blood components rather than whole blood (WB). WB contains all of the individual blood components and has the advantages of simplifying resuscitation logistics, providing physiological ratios of components, reducing preservative volumes and allowing transfusion of younger red blood cells (RBC). Successful experience with fresh whole blood (FWB) by the US military is well documented. In the civilian setting, transfusion of cold-stored low titer type O whole blood (LTOWB) was shown to be safe. Reports of WB are limited by small numbers and low transfusion volumes. STUDY DESIGN We conducted a systematic review of the available published studies, comparing efficacy and safety of resuscitation with WB to resuscitation with blood components, in hemorrhaging trauma patients, using MEDLINE, EMBASE and ISI Web of Science. The main outcomes of interest were 24 hour and 30-day survival, blood product utilization and adverse events. Two reviewers independently abstracted the studies and assessed for bias. Sub-group analyses were pre-planned on the FWB and LTOWB groups separately. RESULTS Out of 126 references identified through our search strategy, five studies met the inclusion criteria. Only one study of FWB showed a significant benefit on 24 hour and 30-day survival. Other studies of both FWB and LTOWB showed no statistically significant difference in survival. There is an apparent benefit in blood product utilization with the use of WB across most studies. There were no reports of transfusion related reactions, however there was an increase in the organ failure rates in the FWB groups. CONCLUSIONS WB was not associated with a significant survival benefit or reduced blood product utilization. Nonetheless, it seems that the use of LTOWB is safe and might carry a significant logistic benefit. The quality of the existing data is poor and further high quality studies are required.

Abstract

Hemostatic resuscitation is currently considered a standard of care for the management of life-threatening hemorrhage, but in some critical settings the access to high quantities of blood components is problematic. Whole blood (WB) transfusion has been proposed as an alternative modality for hemostatic resuscitation of traumatic major bleeding. To assess the efficacy and safety of WB in trauma-associated massive bleeding, we performed a systematic review of the literature. We selected studies comparing WB transfusions to transfusion of blood components (COMP) in massive trauma bleeding; both randomized clinical trial (RCT) and observational studies were considered. The outcomes were mortality (30-day/in-hospital and 24-h mortality) and adverse events/transfusion reactions. The effect sizes were crude odds ratio (OR), adjusted OR and hazard ratio (HR). The methodological quality of studies was assessed using the Cochrane Risk of Bias tool for RCTs, and the ROBIN-1 tool for observational studies. The overall quality of the available evidence was assessed with the GRADE system. One RCT (2 reports) and 6 cohort studies were included (3642 adult patients; 675 receiving WB, 2967 receiving COMP). Three studies were conducted in military setting, and 4 in civilian setting. In the overall analysis, 30-day/in-hospital and 24-h mortality did not differ significantly between groups (very low quality of the evidence due to high risk of bias, imprecision and inconsistency). After adjustment for baseline covariates in three cohort studies, the OR for mortality was significantly lower in WB recipients compared to COMP (OR 0.22; 95% CIs 0.10/0.45) (moderate grade of evidence). Adverse events and transfusion reactions were overlooked and not consistently reported. The available evidence does not allow to draw definite conclusions on the short-term and long-term efficacy and safety of WB transfusion compared to COMP transfusion. Further well designed research is needed.

Abstract

INTRODUCTION Prehospital care in the combat environment has always been of great importance to the U.S. military, and trauma resuscitation has remained a cornerstone. More evidence continues to demonstrate the advantages of intervention with early transfusion of blood products at the point of injury. The military has recognized these benefits; as such, the Department of Defense Joint Trauma System and the Committee on Tactical Combat Casualty Care have developed new advanced resuscitation guidelines, which now encourage the use of whole blood (WB) in the prehospital setting. MATERIALS AND METHODS This general review of peer-reviewed journal articles was performed through an extensive electronic search from the databases of PubMed Central (MEDLINE) and the Cochrane Library. RESULTS Based on this literature search, the current evidence suggests that transfusion with WB is safe and efficacious. Additionally, soldier function is preserved after donating fresh WB in the field. Currently, the collection and implementation of WB is accomplished through several different protocol-driven techniques. CONCLUSION WB has become the favored transfusion product as it provides all of the components of blood in a convenient package that is easy to store and transport. Specifically, group O WB containing low titers of anti-A and -B antibodies has become the transfusion product of choice, offering the ability to universally fluid resuscitate patients despite not knowing their blood group. This new ability to obtain low titer group O WB has transformed the approach to the management of hemorrhagic shock in the prehospital combat environment.

Abstract

BACKGROUND Patients with hemorrhagic shock from trauma often require balanced blood product transfusion with red blood cells, plasma, and platelets. Resuscitation with whole blood resuscitation is becoming a common practice. We performed a systematic review and meta-analysis of studies comparing whole blood transfusion with balanced component therapy in patients suffering from traumatic hemorrhagic shock. METHODS We searched MEDLINE Ovid, EMBASE, and the Cochrane Library for human studies comparing whole blood with component blood therapy published from January 2007 to June 2019. We included studies from both civilian and military settings and that reported 24-hour, in-hospital, or 30-day mortality. We followed the Preferred Reporting Items in Systematic Reviews and Meta-Analyses (PRISMA) guidelines, assessing study quality, publication bias, and heterogeneity. We used meta-analytic models to determine the associations (odds ratio [OR] with 95% confidence interval [CI]) between whole blood transfusion and (1) 24-hour mortality, and (2) in-hospital or 30-day mortality. RESULTS A total of 1759 identified studies, 12 (reporting on n = 8431 patients) met inclusion criteria. There was heterogeneity in the design, setting, interventions, and outcomes of the studies. On meta-analysis, whole blood transfusion was not associated with 24-hour mortality (OR = 0.83; 95% CI = 0.56-1.24) or in-hospital/30-day mortality (OR = 0.79; 95% CI = 0.48-1.31). CONCLUSION In this systematic review and meta-analysis, compared with conventional component transfusion, whole blood was not associated with 24-hour or in-hospital mortality. However, there were important limitations with and heterogeneity among the primary studies. Additional study is needed to determine the effectiveness of whole blood.

Abstract

BACKGROUND Whole blood (WB) is optimal for resuscitation of traumatic haemorrhage. Walking Blood Banks (WBB) provide fresh whole blood (FWB) where conventional blood components or stored, tested WB are not readily available. There is an increasing interest in this as an emergency resilience measure for isolated communities and during crises including the COVID-19 pandemic. We conducted a systematic review and meta-analysis of the available evidence to inform practice. METHODS Standard systematic review methodology was used to obtain studies that reported the delivery of FWB (PROSPERO registry CRD42019153849). Studies that only reported WB from conventional blood banking were excluded. For outcomes, odds ratios (OR) and 95% confidence interval (CI) were calculated using random effects modelling due to high risk of heterogeneity. Quality of evidence was assessed using the GRADE system. RESULTS 27 studies published from 2006 - 2020 reported >10,000 units of FWB for >3000 patients (precise values not available for all studies). Evidence for studies was "low" or "very low" except for one study which was "moderate" in quality. FWB patients were more severely injured than non-FWB patients. Overall, survival was equivalent between FWB and non-FWB groups for 8 studies that compared these (OR 1.00 (95% CI 0.65, 1.55); p=0.61). However, the highest quality study (matched groups for physiological and injury characteristics) reported an adjusted OR of 0.27 (95% CI 0.13-0.58) for mortality for the FWB group; p<0.01. CONCLUSIONS Thousands of units of FWB from WBBs have been transfused in patients following life-threatening haemorrhage. Survival is equivalent for FWB resuscitation when compared to non-FWB, even when patients were more severely injured. Evidence is scarce and of relative low quality and may underestimate potential adverse events. Whereas WBB may be an attractive resilience measure, caution is still advised. WBBs should be subject to prospective evaluation to optimise care and inform policy. LEVEL OF EVIDENCE Therapeutic, level 3.