Whole blood transfusion in the treatment of acute hemorrhage, a systematic review and meta-analysis
The journal of trauma and acute care surgery. 2023
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.
Minimal tactical impact and maximal donor safety after a buddy transfusion: A study on elite soldier performances in both laboratory and field environments
Transfusion. 2021;61 Suppl 1:S32-s42
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.
Effectiveness and safety of whole blood compared to balanced blood components in resuscitation of hemorrhaging trauma patients - A systematic review
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.
The use of whole blood in traumatic bleeding: a systematic review
Internal and emergency medicine. 2020
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.
Patients with massive trauma bleeding (7 studies, n= 3642).
Whole blood (WB) transfusion (n= 675).
Blood components (COMP), (n= 2967).
In the overall analysis, 30-day/in-hospital and 24-h mortality did not differ significantly between groups. After adjustment for baseline covariates in three cohort studies, the odds ratio for mortality was significantly lower in WB recipients compared to COMP. Adverse events and transfusion reactions were overlooked and not consistently reported.
Practical Considerations for a Military Whole Blood Program
Mil Med. 2020
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.
Patients from a prehospital combat environment.
Systematic review on the use of whole blood (WB) in prehospital setting.
The collection and implementation of WB is accomplished through several different protocol-driven techniques. 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.
Whole blood transfusion versus component therapy in trauma resuscitation: a systematic review and meta-analysis
Journal of the American College of Emergency Physicians open. 2020;1(4):633-641
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.
Fresh whole blood from walking blood banks for patients with traumatic hemorrhagic shock: a systematic review and meta-analysis
J Trauma Acute Care Surg. 2020
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.
Trauma, time, and transfusions: a longitudinal analysis of coagulation markers in severely injured trauma patients receiving modified whole blood or component blood products
OBJECTIVE The current study leveraged data from the Early Whole Blood (EWB) trial to explore the effects of modified whole blood (mWB) versus component (COMP) transfusions on coagulation parameters over time using longitudinal statistical methods. STUDY DESIGN AND METHODS The EWB study was a single-center randomized controlled trial, approved by the local IRB. Adult patients at highest-level trauma activations were randomized into mWB or COMP groups. Coagulation status was evaluated (at times 0, 3, 6, 12, and 24 h postadmission) using thrombelastography, platelet aggregometry, and calibrated automated thrombograms. Longitudinal statistical analyses with generalized estimating equations (GEE) were used to evaluate the effects of group, time, transfusion types, and their respective interactions on changes in measured coagulation markers. RESULTS A total of 59 patients were enrolled and adhered to protocol in the EWB trial, 25 in the mWB group, and 34 in the COMP group. Patients in both the mWB and COMP groups demonstrated a significant decline in their thrombelastography parameters during the first 3-6 h, specifically K-time, alpha-angle, maximum amplitude, G, and LY30. Patients receiving mWB exhibited improved thrombin potential than those receiving COMP. Platelet count and function declined over time in both mWB and COMP groups; however, platelet aggregation in response to ristocetin in the mWB group was significantly improved at 12 h compared with the COMP group. The longitudinal GEE model revealed significant group-time interactive effects on the changes in coagulation markers and significant effect of platelet transfusions on improvements in coagulation profile. CONCLUSIONS We observed significant interactive group-time effects, indicating that the types of transfusion as well as the time of transfusion significantly affect the patient's coagulation status. Our pilot data suggest that there is an improvement in platelet function with mWB, but further studies are needed. Regardless, platelet transfusions were associated with improvements in coagulation over time in both the groups.
A randomized controlled pilot trial of modified whole blood versus component therapy in severely injured patients requiring large volume transfusions
Annals of Surgery. 2013;258((4):):527-33.
OBJECTIVES To determine whether resuscitation of severely injured patients with modified whole blood (mWB) resulted in fewer overall transfusions compared with component (COMP) therapy. BACKGROUND For decades, whole blood (WB) was the primary product for resuscitating patients in hemorrhagic shock. After dramatic advances in blood banking in the 1970s, blood donor centers began supplying hospitals with individual components [red blood cell (RBC), plasma, platelets] and removed WB as an available product. However, no studies of efficacy or hemostatic potential in trauma patients were performed before doing so. METHODS Single-center, randomized trial of severely injured patients predicted to large transfusion volume. Pregnant patients, prisoners, those younger than 18 years or with more than 20% total body surface area burns (TBSA) burns were excluded. Patients were randomized to mWB (1 U mWB) or COMP therapy (1 U RBC+ 1 U plasma) immediately on arrival. Each group also received 1 U platelets (apheresis or prepooled random donor) for every 6 U of mWB or 6 U of RBC + 6 U plasma. The study was performed under the Exception From Informed Consent (Food and Drug Administration 21 code of federal regulations [CFR] 50.24). Primary outcome was 24-hour transfusion volumes. RESULTS A total of 107 patients were randomized (55 mWB, 52 COMP therapy) over 14 months. There were no differences in demographics, arrival vitals or laboratory values, injury severity, or mechanism. Transfusions were similar between groups (intent-to-treat analysis). However, when excluding patients with severe brain injury (sensitivity analysis), WB group received less 24-hour RBC (median 3 vs 6, P = 0.02), plasma (4 vs 6, P = 0.02), platelets (0 vs 3, P = 0.09), and total products (11 vs 16, P = 0.02). CONCLUSIONS Compared with COMP therapy, WB did not reduce transfusion volumes in severely injured patients predicted to receive massive transfusion. However, in the sensitivity analysis (patients without severe brain injuries), use of mWB significantly reduced transfusion volumes, achieving the prespecified endpoint of this initial pilot study.