Removing the barriers to prehospital blood: a roadmap to success.

ABSTRACT: This review describes the necessity, evolution, and current state of prehospital blood programs in the United States. Less than 1% of 9-1-1 Ground Emergency Medical Service agencies have been able to successfully implement prehospital blood transfusions as part of a resuscitation strategy for patients in hemorrhagic shock despite estimates that annually between 54,000 and 900,000 patients may benefit from its use. The use of prehospital blood transfusions as a tool for managing hemorrhagic shock has barriers to overcome to ensure it becomes widely available to patients throughout the United States. Barriers include 1) current state Emergency Medical Services clinicians' scope of practice limitations, 2) program costs and reimbursement of blood products, 3) no centralized data collection process for prehospital hemorrhagic shock and patient outcomes, 4) collaboration between prehospital agencies, blood suppliers, and hospital clinicians and transfusion service activities. The following paper identifies barriers and a proposed roadmap to reduce death due to prehospital hemorrhage.

The U.S. Armed Services Blood Program support to U.S. Central Command 2014-2021: Transformation of combat trauma resuscitation through blood product innovation and expansion of blood availability far forward.

BACKGROUND: The United States Armed Services Blood Program (ASBP) faced complex blood supply challenges during two decades of military operations in the U.S. Central Command (CENTCOM) and through an adaptive, responsive, and agile system, gained valuable insights on blood product usage in combat casualty care. STUDY DESIGN AND METHODS: A retrospective review of blood product introduction and utilization trends was compiled from ASBP data collected during CENTCOM operations from 2014 through 2021. RESULTS: During the study period, several blood products were introduced to the CENTCOM area of operations including Low Titer O Whole Blood (LTOWB), Cold-Stored Platelets (CSP), Liquid Plasma (LP), and French Freeze Dried Plasma (FDP) manufactured from U.S. sourced donor plasma, all while expanding Walking Blood Bank capabilities. There was a gradual substitution of component therapy for whole blood; blood utilization peaked in 2017. Transfusion of Fresh Whole Blood (FWB) from Walking Blood Banks decreased as fully pre-tested LTOWB was supplied by the ASBP. LTOWB was initially supplied in citrate-phosphate-dextrose (CPD) anticoagulant (21-day shelf life) but was largely replaced with LTOWB in citrate-phosphate-dextrose-adenine (CPDA-1) anticoagulant (35-day shelf life) by 2019. Implementation of prehospital transfusion and expansion of surgical and resuscitation teams led to an increase in the number of sites receiving blood. DISCUSSION: ASBP introduced new products to its inventory in order to meet changing blood product demands driven by changes in the Joint Trauma System Clinical Practice Guidelines and operational demands. These products were adopted into clinical practice with a resultant evolution in transfusion strategies.

Determining resuscitation outcomes in combat casualties: Design of the Deployed Hemostatic Emergency Resuscitation of Traumatic Exsanguinating Shock (Deployed HEROES) study.

BACKGROUND: During the course of the recent conflicts, the recommendations for resuscitation practices have evolved, but there has been no comprehensive comparative effectiveness study of these resuscitation strategies. The objective of this study was to describe the development and study design of the Deployed Hemostatic Emergency Resuscitation of Traumatic Exsanguinating Shock (Deployed HEROES) study-the first comprehensive analysis of military resuscitation practices in the deployed environment from October 2001 to October 2019. METHODS: This retrospective cohort study uses the Department of Defense Trauma Registry, Armed Services Blood Program database, and Military Trauma Mortality Review, while abstractors will use Theater Medical Data Store and Web Interface Patient Records to collect transfusion timing data. This study includes patients, who received blood products or died before receiving blood, treated at US military medical treatment facilities. The primary endpoints are survival at 6 hours, 24 hours, and 30 days postinjury. Secondary outcomes include infection, renal dysfunction, pulmonary dysfunction, and thromboembolic event. Exposure will be defined by blood product transfusion. Study groups will be frequency matched. Cox proportional hazards will compare patients who received warm fresh whole blood, low titer type-O whole blood, or only component therapy, while using adjustment for type of blood product transfused as a time-dependent covariate. Multilevel mixed-effects logistic regression will determine the effect of incompatible plasma in low titer type-O whole blood. RESULTS: An analysis plan for the Deployed HEROES study was developed with the aim of minimizing bias. CONCLUSION: This study will inform the optimal resuscitation strategies, which will potentially have a substantial impact on combat mortality. If whole blood is found to be the optimal transfusion strategy, this finding will be crucial in future operating environments involving dispersed medical assets. These results will provide critical information necessary for combat casualty care guidelines. LEVEL OF EVIDENCE: Prognostic and epidemiological; Level III.

Joint Trauma System, Defense Committee on Trauma, and Armed Services Blood Program consensus statement on whole blood.

Hemorrhage is the most common mechanism of death in battlefield casualties with potentially survivable injuries. There is evidence that early blood product transfusion saves lives among combat casualties. When compared to component therapy, fresh whole blood transfusion improves outcomes in military settings. Cold-stored whole blood also improves outcomes in trauma patients. Whole blood has the advantage of providing red cells, plasma, and platelets together in a single unit, which simplifies and speeds the process of resuscitation, particularly in austere environments. The Joint Trauma System, the Defense Committee on Trauma, and the Armed Services Blood Program endorse the following: (1) whole blood should be used to treat hemorrhagic shock; (2) low-titer group O whole blood is the resuscitation product of choice for the treatment of hemorrhagic shock for all casualties at all roles of care; (3) whole blood should be available within 30 min of casualty wounding, on all medical evacuation platforms, and at all resuscitation and surgical team locations; (4) when whole blood is not available, component therapy should be available within 30 min of casualty wounding; (5) all prehospital medical providers should be trained and logistically supported to screen donors, collect fresh whole blood from designated donors, transfuse blood products, recognize and treat transfusion reactions, and complete the minimum documentation requirements; (6) all deploying military personnel should undergo walking blood bank prescreen laboratory testing for transfusion transmitted disease immediately prior to deployment. Those who are blood group O should undergo anti-A/anti-B antibody titer testing.

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.

Conducting fresh whole blood transfusion training.

Fresh whole blood is the optimal resuscitation fluid for casualties in hemorrhagic shock according to the Committee on Tactical Combat Casualty Care and has demonstrated to improve outcomes in severely wounded patients. Like all medical interventions, fresh whole blood transfusions are not without risks, but similarly can be mitigated through increased training to develop provider knowledge and proficiency. To date, no literature has been published regarding the proper technique to conduct fresh whole blood transfusion training. This article provides a structured foundation to establish a standardized fresh whole blood transfusion training program to increase skill and preparedness for fresh whole blood protocol implementation. Using these techniques in a training environment, providers will be able to provide optimal resuscitation in hemorrhagic shock in austere environments.

The need for dried plasma - a national issue.

Recent studies have demonstrated that early transfusion of plasma or RBCs improves survival in patients with severe trauma and hemorrhagic shock. Time to initiate transfusion is the critical factor. It is essential that transfusion begin in the prehospital environment when transport times are longer than approximately 15 to 20 minutes. Unfortunately, logistic constraints severely limit the use of blood products in the prehospital setting, especially in military, remote civilian, and mass disaster circumstances, where the need can be most acute. US military requirements for logistically supportable blood products are projected to increase dramatically in future conflicts. Although dried plasma products have been available and safely used in a number of countries for over 20 years, there is no dried plasma product commercially available in the United States. A US Food and Drug Administration-approved dried plasma is urgently needed. Considering the US military, disaster preparedness, and remote civilian trauma perspectives, this is an urgent national health care issue.

Lifeline for the front lines: blood products to support the warfighter.

BACKGROUND: Hemorrhage is the leading cause of death on the battlefield. Damage control resuscitation guidelines in the US military recommend whole blood as the preferred resuscitation product. The Armed Services Blood Program (ASBP) has initiated low-titer group O whole blood (LTOWB) production and predeployment donor screening to make whole blood more available to military forces. STUDY DESIGN AND METHODS: ASBP donor centers updated procedures and labeling for LTOWB production. Donors are screened according to US Food and Drug Administration regulations and standard operating procedures. Group O donors are tested for anti-A and anti-B titer levels. Additionally, military personnel notified for pending deployment coordinate with their local ASBP donor center to complete whole blood donor prescreening. The process consists of completing a donor history questionnaire, processing of blood samples for blood group and infectious disease testing, and titer determination for group O personnel. RESULTS: Since March 2016, 7940 LTOWB units have been manufactured at ASBP donor centers and shipped in support of combat operations. Additionally, ASBP donor centers have screened several thousand service members before deployment. From these screenings, the donor low titer rate was 68% and infectious disease reactive test rate was extremely low (≤0.004). CONCLUSION: Whole blood is now the preferred blood product for resuscitation of combat trauma patients. The ASBP partnered with combat forces to screen personnel before deployment. Additionally, LTOWB is manufactured and shipped in support of combat operations. These efforts are expanding the availability of LTOWB for the warfighter.

Theater Blood Support in the Prehospital Setting.

The Army Blood Program (ABP) is charged with the responsibility of supporting the Warfighter on the battlefield, in addition to meeting garrison hospital blood requirements on a daily basis. Blood support concepts developed in response to Operation Iraqi Freedom/Operation Enduring Freedom combat operations are the cornerstone to maintaining current capabilities and shaping future endeavors.. The ABP is actively engaged with research, advanced development of blood products and medical technology to improve blood safety and efficacy for both our conventional and operational forces. The feasibility of frozen/deglycerolized red blood cell use in theater has been demonstrated. The use of Blood Group A plasma in the place of Blood Group AB plasma has been successful. Placement of cryoprecipitate at Role 2 medical facilities and the placement of blood products on MEDEVAC (Vampire Program missions) have proven invaluable in moving transfusion therapy closer to the point of Injury. The improved patient outcomes from earlier transfusion of blood products has driven the requirement for far-forward blood support. Now (more than ever), there are products and processes in place to meet the requirements for blood use in the prehospital setting.

NATO Blood Panel perspectives on changes to military prehospital resuscitation policies: current and future practice.

The North Atlantic Treaty Organization (NATO) Blood Panel exists to promote interoperability of transfusion practice between NATO partners. However, it has served as an important forum for the development of prehospital transfusion and transfusion in the austere environment. There are synergies with the trauma hemostasis and oxygen research community especially in the areas of innovation and research. Four presentations are summarized together with a review of some scientific principles. The past decade has already seen significant changes in early transfusion support. Sometimes practice has preceded the evidence and has stretched regulatory and logistic constraints. Ethical and philosophical issues are also important and require us to question "should we" and not just "could we." The challenge for the combined communities is to continue to optimize transfusion support underpinned by evidence-based excellence.

Treatment of blood with a pathogen reduction technology using ultraviolet light and riboflavin inactivates Ebola virus in vitro.

BACKGROUND: Transfusion of plasma from recovered patients after Ebolavirus (EBOV) infection, typically called "convalescent plasma," is an effective treatment for active disease available in endemic areas, but carries the risk of introducing other pathogens, including other strains of EBOV. A pathogen reduction technology using ultraviolet light and riboflavin (UV+RB) is effective against multiple enveloped, negative-sense, single-stranded RNA viruses that are similar in structure to EBOV. We hypothesized that UV+RB is effective against EBOV in blood products without activating complement or reducing protective immunoglobulin titers that are important for the treatment of Ebola virus disease (EVD). STUDY DESIGN AND METHODS: Four in vitro experiments were conducted to evaluate effects of UV+RB on green fluorescent protein EBOV (EBOV-GFP), wild-type EBOV in serum, and whole blood, respectively, and on immunoglobulins and complement in plasma. Initial titers for Experiments 1 to 3 were 4.21 log GFP units/mL, 4.96 log infectious units/mL, and 4.23 log plaque-forming units/mL. Conditions tested in the first three experiments included the following: 1-EBOV-GFP plus UV+RB; 2-EBOV-GFP plus RB only; 3-EBOV-GFP plus UV only; 4-EBOV-GFP without RB or UV; 5-virus-free control plus UV only; and 6-virus-free control without RB or UV. RESULTS: UV+RB reduced EBOV titers to nondetectable levels in both nonhuman primate serum (≥2.8- to 3.2-log reduction) and human whole blood (≥3.0-log reduction) without decreasing protective antibody titers in human plasma. CONCLUSION: Our in vitro results demonstrate that the UV+RB treatment efficiently reduces EBOV titers to below limits of detection in both serum and whole blood. In vivo testing to determine whether UV+RB can improve convalescent blood product safety is indicated.

US Army blood program: 2025 and beyond.

In preparing to support the Army in 2025 and beyond, the Army Blood Program remains actively engaged with the research and advanced development of blood products and medical technology to improve blood safety and efficacy in conjunction with the US Army Medical Research and Materiel Command. National and International Blood Bank authorities have noted that the US Army research and development efforts in providing new blood products and improving blood safety operate on the cutting edge of technology and are transformational for the global blood industry. Over the past 14 years, the Army has transformed how blood support is provided and improved the survival rate of casualties. Almost every product or process developed by or for the military has found an application in treating civilian patients. Conflicts have many unwanted consequences; however, in times of conflict, one positive aspect is the identification of novel solutions to improve the safety and efficacy of the blood supply.