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

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

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.