U.S. cities will not meet blood product resuscitation standards during major mass casualty incidents: Results of a THOR-AABB working party prospective analysis.

BACKGROUND: Mass casualty incidents (MCIs) create an immediate surge in blood product demand. We hypothesize local inventories in major U.S. cities would not meet this demand. STUDY DESIGN AND METHODS: A simulated blast in a large crowd estimated casualty numbers. Ideal resuscitation was defined as equal amounts of red blood cells (RBCs), plasma, platelets, and cryoprecipitate. Inventory was prospectively collected from six major U.S. cities at six time points between January and July 2019. City-wide blood inventories were classified as READY (>1 U/injured survivor), DEFICIENT (<10 U/severely injured survivor), or RISK (between READY and DEFICIENT), before and after resupply from local distribution centers (DC), and features of DEFICIENT cities were identified. RESULTS: The simulated blast resulted in 2218 injured survivors including 95 with severe injuries. Balanced resuscitation would require between 950 and 2218 units each RBC, plasma, platelets and cryoprecipitate. Inventories in 88 hospitals/health systems and 10 DCs were assessed. Of 36 city-wide surveys, RISK inventories included RBCs (n = 16; 44%), plasma (n = 24; 67%), platelets (n = 6; 17%), and cryoprecipitate (n = 22; 61%) while DEFICIENT inventories included platelets (n = 30; 83%) and cryoprecipitate (n = 12; 33%). Resupply shifted most RBC and plasma inventories to READY, but some platelet and cryoprecipitate inventories remained at RISK (n = 24; 67% and n = 12; 33%, respectively) or even DEFICIENT (n = 11; 31% and n = 6; 17%, respectively). Cities with DEFICIENT inventories were smaller (p <.001) with fewer blood products per trauma bed (p <.001). DISCUSSION: In this simulated blast event, blood product demand exceeded local supply in some major U.S. cities. Options for closing this gap should be explored to optimize resuscitation during MCIs.

Resuscitation with blood products in patients with trauma-related haemorrhagic shock receiving prehospital care (RePHILL): a multicentre, open-label, randomised, controlled, phase 3 trial.

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.

Training trial of critical care paramedics for non-medical authorisation of blood.

The use of pre-hospital blood transfusion by air ambulance crews is increasing. Blood transfusion is traditionally 'authorised' by doctors, not prescribed. However, there is an increasing interest in extending the capability of authorisation to other practitioners - that is, non-medical authorisation (NMA). A UK framework for nurses and midwives has existed since 2007, but training for critical care paramedics (CCPs) has been limited. The Resuscitation with Pre-Hospital Blood Products (RePHILL) trial was launched in 2016, requiring pre-hospital administration of red cells and LyoPlas. Authorisation was initially restricted to doctors, leading to missed recruitment by paramedic-only crews. The trial protocol was amended in 2019 to permit NMA following suitable training and stakeholder consultation. We present a targeted training programme designed to support paramedic-led transfusion within the framework of the pre-hospital trial. We considered the knowledge and skills required for NMA and compared this with baseline knowledge from paramedic training to identify the training gap. We examined examples of existing military and civilian NMA training to develop a targeted programme for a single air ambulance. The four elements of our training programme were pre-course online training, previous trial participation, face-to-face training and competency assessment. Training was delivered to three CCPs, who cascaded the training to 14 colleagues. The training time was one morning, including a face-to-face session and assessment. Novel topics included physiological triggers for transfusion and transfusion risks in the pre-hospital environment. Paramedics were encouraged to recognise and report new patterns of adverse events. Reflective feedback suggests the programme provided CCPs the knowledge to autonomously recruit trial patients and authorise transfusion.

Transfusion support during mass casualty events.

Transfusion support is an essential element of modern emergency healthcare. Blood services together with hospital transfusion teams are required to prepare for, and respond to, mass casualty events as part of wider healthcare emergency planning. Preparedness is a constant collaborative process that actively identifies and manages potential risks, to prevent such events becoming a 'disaster'. The aim of transfusion support during incidents is to provide sufficient and timely supply of blood components and diagnostic services, whilst maintaining support to other patients not involved in the event.

Evaluating apheresis platelets at reduced dose as a contingency measure for extreme shortages.

BACKGROUND: The COVID19 pandemic highlights the need for contingency planning in the event of blood shortages. To increase platelet supply, we assessed the operational impact and effect on platelet quality of splitting units prior to storage. STUDY DESIGN AND METHODS: Using production figures, we modeled the impact on unit numbers, platelet counts, and volumes of splitting only apheresis double donations into three units (yielding ⅔ doses), or all standard dose units in half. To assess quality, eight pools of three ABO/Rh-matched apheresis (Trima Accel) double donations in plasma were split to ⅔ and ½ volumes in both Terumo and Fresenius storage bags. These were irradiated and subject to maximal permitted periods of nonagitation (3 × 8 h) before comparing platelet quality markers (including pH, CD62P expression) to Day 9 of storage. RESULTS: Splitting all double donations into three predicted inventory expansion of 23% overall whereas halving all standard dose units clearly doubles stock. In our study, ⅔ and ½ doses contained 153 ± 15 × 109 (~138 ml) and 113 ± 11 × 109 (~102 ml) platelets respectively. Following storage, higher pH was observed in ⅔ than in ½ doses and in Terumo compared to Fresenius bags. The higher pH was reflected in better quality markers, including lower CD62P expression. Despite the differences, on Day 8 (of pH monitoring at expiry) all ⅔ doses and most ½ doses were ≥pH 6.4. CONCLUSION: A strategy to split apheresis platelets in plasma to lower doses is feasible, maintains acceptable platelet quality, and should be considered by blood services in response to extreme shortages.

Civilian walking blood bank emergency preparedness plan.

BACKGROUND: The current global pandemic has created unprecedented challenges in the blood supply network. Given the recent shortages, there must be a civilian plan for massively bleeding patients when there are no blood products on the shelf. Recognizing that the time to death in bleeding patients is less than 2 h, timely resupply from unaffected locations is not possible. One solution is to transfuse emergency untested whole blood (EUWB), similar to the extensive military experience fine-tuned over the last 19 years. While this concept is anathema in current civilian transfusion practice, it seems prudent to have a vetted plan in place. METHODS AND MATERIALS: During the early stages of the 2020 global pandemic, a multidisciplinary and international group of clinicians with broad experience in transfusion medicine communicated routinely. The result is a planning document that provides both background information and a high-level guide on how to emergently deliver EUWB for patients who would otherwise die of hemorrhage. RESULTS AND CONCLUSIONS: Similar plans have been utilized in remote locations, both on the battlefield and in civilian practice. The proposed recommendations are designed to provide high-level guidance for experienced blood bankers, transfusion experts, clinicians, and health authorities. Like with all emergency preparedness, it is always better to have a well-thought-out and trained plan in place, rather than trying to develop a hasty plan in the midst of a disaster. We need to prevent the potential for empty shelves and bleeding patients dying for lack of blood.

Temperature mapping in an air ambulance helicopter: Implications for the delivery of pre-hospital transfusion.

BACKGROUND: Pre-hospital blood products, including freeze-dried plasma, are increasingly carried on air ambulance helicopters. The purpose of this study was to map the temperatures within a civilian air ambulance and consider the implications for pre-hospital transfusion. MATERIALS AND METHODS: We conducted a single-site prospective observational study in the United Kingdom. Tinytag temperature data-loggers (Gemini, UK) were secured on to three locations throughout an air ambulance, and one was placed inside an insulated drug-pouch. Temperatures were monitored at 5-min intervals. Data were downloaded monthly and processed using R and MKT software to collate maximum, minimum, and day/night mean kinetic temperatures (MKTs). Blood was transported in Credo ProMed 4 containers (Peli Products, S.L.U) and monitored with QTA data-loggers (Tridentify, Sweden). RESULTS: A total of 344,844 temperature recordings were made on 302 days during a 12-month period from January 2019. The external ambient temperatures varied seasonally from -7.1°C to 31.2°C, whereas internal temperatures ranged from -0.3°C to 60.6°C. The warmest area was alongside the left front-crew position (range 1.9-60.6°C, MKT 24.8°C). The lowest daytime MKT (16.9°C) and range (1.7°C-36.4°C) were recorded next to the patient stretcher. Temperatures ranged from 4.2°C to 40.1°C inside the insulated drugs-pouch, exceeding 25°C on 47 days (15%) and falling below 15°C on 192 days (63%) In contrast, thermally packed blood maintained a range of 2-6°C. CONCLUSION: The temperatures within an air ambulance varied throughout the cabin and often exceeded the external ambient temperature. Appropriately selected thermal protection and monitoring is required for the successful delivery of pre-hospital transfusion, even in a temperate climate.

Effect of parachute delivery on red blood cell (RBC) and plasma quality measures of blood for transfusion.

BACKGROUND: Parachute airdrop offers a rapid transfusion supply option for humanitarian aid and military support. However, its impact on longer-term RBC survival is undocumented. This study aimed to determine post-drop quality of RBCs in concentrates (RCC), and both RBCs and plasma in whole blood (WB) during subsequent storage. STUDY DESIGN AND METHODS: Twenty-two units of leucodepleted RCC in saline, adenine, glucose, mannitol (SAGM) and 22 units of nonclinical issue WB were randomly allocated for air transportation, parachute drop, and subsequent storage (parachute), or simply storage under identical conventional conditions (4 ± 2°C) (control). All blood products were 6-8 days post-donation. Parachute units were packed into Credo Cubes, (Series 4, 16 L) inside a PeliCase (Peli 0350) and rigged as parachute delivery packs. Packs underwent a 4-h tactical flight (C130 aircraft), then parachuted from 250 to 400 ft before ground recovery. The units were sampled aseptically before and after airdrop at weekly intervals. A range of assays quantified the RBC storage lesion and coagulation parameters. RESULTS: Blood units were maintained at 2-6°C and recovered intact after recorded ground impacts of 341-1038 m s-2 . All units showed a classical RBC storage lesion and increased RBC microparticles during 42 days of storage. Fibrinogen and clotting factors decreased in WB during storage. Nevertheless, no significant difference was observed between Control and Parachute groups. Air transportation and parachute delivery onto land did not adversely affect, or shorten, the shelf life of fresh RBCs or WB. DISCUSSION: Appropriately packaged aerial delivery by parachute can be successfully used for blood supply.

Ebola virus antibody decay-stimulation in a high proportion of survivors.

Neutralizing antibody function provides a foundation for the efficacy of vaccines and therapies1-3. Here, using a robust in vitro Ebola virus (EBOV) pseudo-particle infection assay and a well-defined set of solid-phase assays, we describe a wide spectrum of antibody responses in a cohort of healthy survivors of the Sierra Leone EBOV outbreak of 2013-2016. Pseudo-particle virus-neutralizing antibodies correlated with total anti-EBOV reactivity and neutralizing antibodies against live EBOV. Variant EBOV glycoproteins (1995 and 2014 strains) were similarly neutralized. During longitudinal follow-up, antibody responses fluctuated in a 'decay-stimulation-decay' pattern that suggests de novo restimulation by EBOV antigens after recovery. A pharmacodynamic model of antibody reactivity identified a decay half-life of 77-100 days and a doubling time of 46-86 days in a high proportion of survivors. The highest antibody reactivity was observed around 200 days after an individual had recovered. The model suggests that EBOV antibody reactivity declines over 0.5-2 years after recovery. In a high proportion of healthy survivors, antibody responses undergo rapid restimulation. Vigilant follow-up of survivors and possible elective de novo antigenic stimulation by vaccine immunization should be considered in order to prevent EBOV viral recrudescence in recovering individuals and thereby to mitigate the potential risk of reseeding an outbreak.

London 2017: Lessons learned in transfusion emergency planning.

BACKGROUND AND OBJECTIVES: Hospitals prepare for emergencies, but the impact on transfusion staff is rarely discussed. We describe the transfusion response to four major incidents (MIs) during a 6-month period. Three events were due to terrorist attacks, and the fourth was the Grenfell Tower fire. The aim of this paper was to share the practical lessons identified. METHODS: This was a retrospective review of four MIs in 2017 using patient administration systems, MI documentation and post-incident debriefs. Blood issue, usage and adverse events during the four activation periods were identified using the Laboratory Information Management System (TelePath). RESULTS: Thirty-four patients were admitted (18 P1, 4 P2, 11 P3 and 1 dead). Forty-five blood samples were received: 24 related to nine MI P1 patients. Four P1s received blood components, three with trauma and one with burns, and 35 components were issued. Total components used were six red blood cells (RBC), six fresh frozen plasma (FFP) and two cryoprecipitate pools. Early lessons identified included sample labelling errors (4/24). Errors resolved following the deployment of transfusion staff within the emergency department. Components were over-ordered, leading to time-expiry wastage of platelets. Careful staff management ensured continuity of transfusion services beyond the immediate response period. Debriefing sessions provided staff with support and enabled lessons to be shared. CONCLUSIONS: Transfusion teams were involved in repeated incidents. The demand for blood was minimal. Workload was related to sample handling rather than component issue. A shared situational awareness would improve stock management. A laboratory debriefing system offered valuable feedback for service improvement, staff training and support.

Re-introducing whole blood for transfusion: considerations for blood providers.

Whole blood is the original blood preparation but disappeared from the blood bank inventories in the 1980s following the advent of component therapy. In the early 2000s, both military and civilian practice called for changes in the transfusion support for massive haemorrhage. The 'clear fluid' policy was abandoned and replaced by early balanced transfusion of platelets, plasma and red cells. Whole blood is an attractive alternative to multi-component therapy, which offers reduced hemodilution, lower donor exposure and simplified logistics. However, the potential for wider re-introduction of whole blood requires re-evaluation of haemolysins, storage conditions and shelf-life, the need for leucocyte depletion/ pathogen reduction and inventory management for blood providers. This review addresses these questions and calls for research to define the optimal whole blood product and the indications for its use.

Fresh whole blood from walking blood banks for patients with traumatic hemorrhagic shock: A systematic review and meta-analysis.

BACKGROUND: Whole blood is optimal for resuscitation of traumatic hemorrhage. Walking Blood Banks provide fresh whole blood (FWB) where conventional blood components or stored, tested whole blood are not readily available. There is an increasing interest in this as an emergency resilience measure for isolated communities and during crises including the coronavirus disease 2019 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 whole blood from conventional blood banking were excluded. For outcomes, odds ratios (ORs) and 95% confidence interval (CI) were calculated using random-effects modeling because of high risk of heterogeneity. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation system. RESULTS: Twenty-seven studies published from 2006 to 2020 reported >10,000 U of FWB for >3,000 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. Fresh whole blood patients were more severely injured than non-FWB patients. Overall, survival was equivalent between FWB and non-FWB groups for eight 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). CONCLUSION: Thousands of units of FWB from Walking Blood Banks have been transfused in patients following life-threatening hemorrhage. Survival is equivalent for FWB resuscitation when compared with non-FWB, even when patients were more severely injured. Evidence is scarce and of relative low quality and may underestimate potential adverse events. Whereas Walking Blood Banks may be an attractive resilience measure, caution is still advised. Walking Blood Banks should be subject to prospective evaluation to optimize care and inform policy. LEVEL OF EVIDENCE: Systematic/therapeutic, level 3.

Triage tool for the rationing of blood for massively bleeding patients during a severe national blood shortage: guidance from the National Blood Transfusion Committee.

The emerging COVID-19 pandemic has overwhelmed healthcare resources worldwide, and for transfusion services this could potentially result in rapid imbalance between supply and demand due to a severe shortage of blood donors. This may result in insufficient blood components to meet every patient's needs resulting in difficult decisions about which patients with major bleeding do and do not receive active transfusion support. This document, which was prepared on behalf of the National Blood Transfusion Committee in England, provides a framework and triage tool to guide the allocation of blood for patients with massive haemorrhage during severe blood shortage. Its goal is to provide blood transfusions in an ethical, fair, and transparent way to ensure that the greatest number of life years are saved. It is based on an evidence- and ethics-based Canadian framework, and would become operational where demand for blood greatly exceeds supply, and where all measures to manage supply and demand have been exhausted. The guidance complements existing national shortage plans for red cells and platelets.

Emergency preparedness, resilience and response guidance for UK hospital transfusion teams.

OBJECTIVES: To present Emergency Preparedness, Resilience and Response (EPRR) guidance for Hospital Transfusion Teams on behalf of the National Blood Transfusion Committee emergency planning working group. BACKGROUND: The Civil Contingencies Act 2004 requires healthcare organisations to demonstrate that they can deal with major incidents while maintaining critical services. Recent mass casualty events and the use of transfusion-based resuscitation have highlighted the evolving role of the Hospital Transfusion Team. METHODS: This multi-disciplinary advice is informed by recent global and national experience, the 2018 NHS England clinical guidelines for Major Incidents, and stakeholder workshops. GUIDANCE: Transfusion staff should be familiar with local EPRR plans including casualty type and numbers. Staff should be exercised as part of wider Trust preparation, with documented roles and responsibilities. Transfusion support should be proactive and include blood issue, regulatory compliance and sample handling. Robust LIMS-compatible emergency identification systems are essential to minimise errors. Emergency stock management requires rapid assessment of existing stock and estimated demand before re-ordering. Initial demand should be based on 2 to 4 red blood cells (RBC) per patient admitted. Patients with significant haemorrhage may require further red cells and early haemostatic support. Where "universal" components are demanded, they should be gender appropriate. Senior staff should lead the response, log and communicate key decisions, and prepare for post-incident recovery. CONCLUSIONS: Transfusion teams have an important role in ensuring continuity of transfusion support. Teams should develop their EPRR plans based on local plans and national guidance. Emergency preparedness should include post-incident debriefing for ongoing staff support and future service improvement.