The thin red line: Blood planning factors and the enduring need for a robust military blood system to support combat operations.

ABSTRACT: Battlefield lessons learned are forgotten; the current name for this is the Walker Dip. Blood transfusion and the need for a Department of Defense Blood Program are lessons that have cycled through being learned during wartime, forgotten, and then relearned during the next war. The military will always need a blood program to support combat and contingency operations. Also, blood supply to the battlefield has planning factors that have been consistent over a century. In 2024, it is imperative that we codify these lessons learned. The linchpins of modern combat casualty care are optimal prehospital care, early whole blood transfusion, and forward surgical care. This current opinion comprised of authors from all three military Services, the Joint Trauma System, the Armed Services Blood Program, blood SMEs and the CCC Research Program discuss two vital necessities for a successful military trauma system: (1) the need for an Armed Services Blood Program and (2) Planning factors for current and future deployed military ere is no effective care for wounded soldiers, and by extension there is no effective military medicine.

Blood consumption in the Role 2 setting: A Department of Defense Trauma Registry analysis.

BACKGROUND: The Role 2 setting represents the most far-forward military treatment facility with limited surgical and holding capabilities. There are limited data to guide recommendations on blood product utilization at the Role 2. We describe the consumption of blood products in this setting. STUDY DESIGN AND METHODS: We analyzed data from 2007 to 2023 from the Department of Defense Trauma Registry (DODTR) that received care at a Role 2. We used descriptive and inferential statistics to characterize the volumes of blood products consumed in this setting. We also performed a secondary analysis of US military, Coalition, and US contractor personnel. RESULTS: Within our initial cohort analysis of 15,581 encounters, 17% (2636) received at least one unit of PRBCs or whole blood, of which 11% received a submassive transfusion, 4% received a massive transfusion, and 1% received a supermassive transfusion. There were 6402 encounters that met inclusion for our secondary analysis. With this group, 5% received a submassive transfusion, 2% received a massive transfusion, and 1% received a supermassive transfusion. CONCLUSIONS: We described volumes of blood products consumed at the Role 2 during recent conflicts. The maximum number of units consumed among survivors exceeds currently recommended available blood supply. Our findings suggest that rapid resupply and cold-stored chain demands may be higher than anticipated in future conflicts.

Finding the bleeding edge: 24-hour mortality by unit of blood product transfused in combat casualties from 2002-2020.

BACKGROUND: Transfusion studies in civilian trauma patients have tried to identify a general futility threshold. We hypothesized that in combat settings there is no general threshold where blood product transfusion becomes unbeneficial to survival in hemorrhaging patients. We sought to assess the relationship between the number of units of blood products transfused and 24-hour mortality in combat casualties. METHODS: A retrospective analysis of the Department of Defense Trauma Registry supplemented with data from the Armed Forces Medical Examiner. Combat casualties who received at least one unit of blood product at US military medical treatment facilities (MTFs) in combat settings (2002-2020) were included. The main intervention was the total units of any blood product transfused, which was measured from the point of injury until 24 hours after admission from the first deployed MTF. The primary outcome was discharge status (alive, dead) at 24 hours from time of injury. RESULTS: Of 11,746 patients included, the median age was 24 years, and most patients were male (94.2%) with penetrating injury (84.7%). The median injury severity score was 17 and 783 (6.7%) patients died by 24 hours. Median units of blood products transfused was 8. Most blood products transfused were red blood cells (50.2%), followed by plasma (41.1%), platelets (5.5%), and whole blood (3.2%). Among the 10 patients who received the most units of blood product (164 units to 290 units), 7 survived to 24 hours. The maximum amount of total blood products transfused to a patient who survived was 276 units. Of the 58 patients who received over 100 units of blood product, 20.7% died by 24 hours. CONCLUSION: While civilian trauma studies suggest the possibility of futility with ultra-massive transfusion, we report that the majority (79.3%) of combat casualties who received transfusions greater than 100 units survived to 24 hours. These results do not support a threshold for futility of blood product transfusion. Further analysis as to predictors for mortality will help in situations of blood product and resource constraints. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

A prospective assessment of the time required to obtain one unit of fresh whole blood by civilian phlebotomists and Army laboratory technicians (68 K).

BACKGROUND: Resuscitation with blood products improves survival after major hemorrhage. Blood product administration at or near the point-of-injury (POI) amplifies this benefit. Size, weight, and cold-chain management challenges all limit the amount of blood medics can carry. Warm fresh whole blood (WFWB) transfusions from a pre-screened donor within the unit represent an alternative source of blood at the POI. We measured the time required for civilian and Army technicians performing phlebotomy frequently to obtain one unit of blood to serve as a goal metric for combat medics being trained in this skill. METHODS: We gathered demographic and experience data along with proportion of first intravenous cannulation attempt success, time to blood flow initiated, and time to unit draw complete. RESULTS: We prospectively enrolled 12 civilian phlebotomy technicians and 10 Army laboratory technicians performing whole blood collections on 50 and 68 donors respectively. The mean time from setup to needle insertion was 3.7 min for civilians versus 4.2 min for Army technicians. The mean time from blood flowing to the bag being full was 10.7 min versus 8.4 min for civilians versus Army technicians respectively. The mean bag weights were 514 g versus 522 g. First-pass intravenous cannulation success was 96% versus 98% respectively. CONCLUSIONS: We found a high first intravenous cannulation attempt success among both the civilian and Army technicians. Medians times were <5 min to obtain venipuncture and <11 min to obtain one unit. These findings provide time-based benchmarks for potential use during transfusion training among military medics.

A prospective assessment of the medic autologous blood transfusion skills for field transfusion preparation.

BACKGROUND: Data demonstrate the benefit of blood product administration near point-of-injury (POI). Fresh whole blood transfusion from a pre-screened donor provides a source of blood at the POI when resources are constrained. We captured transfusion skills data for medics performing autologous blood transfusion training. METHODS: We conducted a prospective, observational study of medics with varying levels of experience. Inexperienced medics were those with minimal or no reported experience learning the autologous transfusion procedures, versus reported experience among special operations medics. When available, medics were debriefed after the procedure for qualitative feedback. We followed them for up to 7 days for adverse events. RESULTS: The median number of attempts for inexperienced and experienced medics was 1 versus 1 (interquartile range 1-1 for both, p = .260). The inexperienced medics had a slower median time to needle venipuncture access for the donation of 7.3 versus 1.5 min, needle removal after clamping time of 0.3 versus 0.2 min, time to bag preparation of 1.9 versus 1.0 min, time to IV access for reinfusion of 6.0 versus 3.0 min, time to transfusion completion of 17.3 versus 11.0 min, and time to IV removal of 0.9 versus 0.3 min (all p < .05). We noted one administrative safety event in which an allogeneic transfusion occurred. No major adverse events occurred. Qualitative data saturated around the need for quarterly training. CONCLUSIONS: Inexperienced medics have longer procedure times when training autologous whole blood transfusion skills. This data will help establish training measures of performance for skills optimization when learning this procedure.

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.

Coagulation function of never frozen liquid plasma stored for 40 days.

BACKGROUND: Never frozen liquid plasma (LP) has limited shelf life versus fresh frozen plasma (FFP) or plasma frozen within 24 h (PF24). Previous studies showed decreasing factor activities after Day (D)14 in thawed FFP but no differences between LP and FFP until D10. This study examined LP function through D40. STUDY DESIGN AND METHODS: FFP and PF24 were stored at -20°C until assaying. LP was assayed on D5 then stored (4°C) for testing through D40. A clinical coagulation analyzer measured Factor (F)V, FVIII, fibrinogen, prothrombin time (PT), and activated partial thromboplastin time (aPTT). Thromboelastography (TEG) and thrombogram measured functional coagulation. Ristocetin cofactor assay quantified von Willebrand factor (vWF) activity. Residual platelets were counted. RESULTS: FV/FVIII showed diminished activity over time in LP, while PT and aPTT both increased over time. LP vWF declined significantly by D7. Fibrinogen remained high through D40. Thrombin lagtime was delayed in LP but consistent to D40, while peak thrombin was significantly lower in LP but did not significantly decline over time. TEG R-time and angle remained constant. LP and PF24 (with residual platelets) had initially higher TEG maximum amplitudes (MA), but by D14 LP was similar to FFP. CONCLUSION: Despite significant declines in some factors in D40 LP, fibrinogen concentration and TEG MA were stable suggesting stored LP provides fibrinogen similarly to frozen plasmas even at D40. LP is easier to store and prepare for prehospital transfusion, important benefits when the alternative is crystalloid.

Low titer group O whole blood resuscitation: Military experience from the point of injury.

INTRODUCTION: In the far forward combat environment, the use of whole blood is recommended for the treatment of hemorrhagic shock after injury. In 2016, US military special operations teams began receiving low titer group O whole blood (LTOWB) for use at the point of injury (POI). This is a case series of the initial 15 patients who received LTOWB on the battlefield. METHODS: Patients were identified in the Department of Defense Trauma Registry, and charts were abstracted for age, sex, nationality, mechanism of injury, injuries and physiologic criteria that triggered the transfusion, treatments at the POI, blood products received at the POI and the damage-control procedures done by the first surgical team, next level of care, initial interventions by the second surgical team, Injury Severity Score, and 30-day survival. Descriptive statistics were used to characterize the clinical data when appropriate. RESULTS: Of the 15 casualties, the mean age was 28, 50% were US military, and 63% were gunshot wounds. Thirteen patients survived to discharge, one died of wounds after arrival at the initial resuscitative surgical care, and two died prehospital. The mean Injury Severity Score was 21.31 (SD, 18.93). Eleven (68%) of the causalities received additional blood products during evacuation/role 2 and/or role 3. Vital signs were available for 10 patients from the prehospital setting and 9 patients upon arrival at the first surgical capable facility. The mean systolic blood pressure was 80.5 prehospital and 117 mm Hg (p = 0.0002) at the first surgical facility. The mean heart rate was 105 beats per minute prehospital and 87.4 beats per minute (p = 0.075) at the first surgical facility. The mean hospital stay was 24 days. CONCLUSION: The use of cold-stored LTOWB at POI is feasible during combat operations. Further data are needed to validate and inform best practice for POI transfusion. LEVEL OF EVIDENCE: Therapeutic study, level V.

Field-expedient thawing of fresh-frozen plasma.

INTRODUCTION: Frozen plasma is superior to crystalloids for hemorrhage resuscitation but remains logistically challenging in austere environments because of specialized clinical equipment for on-demand thawing. This research examines some ad hoc thawing techniques that have been implemented by military medical personnel. METHODS: Fresh-frozen plasma (FFP) units were thawed accordingly: using a slow cooker (three temperature settings) with preheated or room temperature water; affixing flameless ration heaters from meals ready-to-eat (MREs) to FFP and submerging in water; exposing FFP to electric kettle-boiled water; incubating with a sous vide immersion circulator; or using a clinical thawer (control). Hemostatic function, thrombin generation, factor activities, and essential chemistry were measured after thawing. RESULTS: Even at the highest temperatures, without preheated water the slow cooker doubled thawing time (62.5 min vs. control, 32.5 min; p < 0.0001), and the final temperature was 13.5°C versus 28.8°C in control (p < 0.01). When preheated, the slow cooker thawed in 31.3 minutes (p < 0.05), with a final temperature of 22.4°C. Kettle-boiled water thawed in 23.0 minutes with a final temperature of 25.1°C. The sous vide thawed in 28.1 minutes, with a final temperature of 20.2°C. MRE heaters were insufficient. Functional measures were similar in all conditions. DISCUSSION: In emergencies, protracted plasma thawing is unacceptable, and slower thawing methods also produced cryoprecipitate. Although no functional changes were observed with boiled water thawing, potential negative physiological impacts must be examined. Safe, controlled thawing can be obtained with the sous vide, although optimization requires further testing.

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.

Hemostatic characteristics of thawed, pooled cryoprecipitate stored for 35 days at refrigerated and room temperatures.

BACKGROUND: Cryoprecipitate's shelf life is limited due to concerns over decreased clotting factor activity and contamination with extended storage. Hemostatic characteristics of thawed cryoprecipitate stored up to 35 days at refrigerated and room temperatures were assessed. STUDY DESIGN AND METHODS: Pooled cryoprecipitate was thawed and aliquoted for storage at 1-6°C or 21-24°C. Samples were tested immediately after thawing and at 4 h, 24 h, 72 h, and weekly for 35 days. At each time point fibrinogen, factor VIII (FVIII), and von Willebrand factor (vWF) were assessed. Thrombin generation and rotational thromboelastometry (ROTEM) were also performed. Further, packed red cells, platelet concentrates, frozen plasma, and stored cryoprecipitate were combined (1:1:1:1) to simulate massive transfusion and analyzed by ROTEM. Day 35 samples were cultured for bacterial contamination. RESULTS: Precipitation was observed in refrigerated samples; however, these aggregates were easily resuspended upon warming in a 37°C water bath. No significant changes were observed in fibrinogen concentration or ROTEM at either temperature. FVIII and vWF declined significantly during storage. vWF, clot time, and thrombin generation were significantly better preserved with refrigeration. With simulated massive transfusion, fibrinogen function remained at or above the established range for whole blood at both storage temperatures. Bacterial contamination was not observed in cold stored or room temperature cryoprecipitate. CONCLUSION: The fibrinogen concentration and function of cryoprecipitate at extended storage durations are adequate for fibrinogen replacement in critical bleeding. These results support extension of the shelf life of cryoprecipitate when used for fibrinogen replacement.

Changes in donor antibody titer levels over time in a military group O low-titer whole blood program.

BACKGROUND: The ability to rapidly administer whole blood (WB) at the point of injury is an important intervention to save lives. This can be accomplished using low titer group O WB donors. Titers of immunoglobulin M anti-A and anti-B might change over time. This study describes titer testing in a large series of donors. STUDY DESIGN AND METHODS: Data were collected retrospectively from the Armed Services Blood Program and the Theater Medical Data Store. Soldiers assigned to the 75th Ranger Regiment were screened and titered upon completion of training or before deployment or during periodic unit readiness activities. A Ranger group O low-titer (ROLO) donor was defined as having titers of both anti-A and -B of less than 256 by immediate spin testing. RESULTS: Between May 2015 and January 2017, of a total of 2237 participating soldiers, 1892 (84.5%) soldiers underwent antibody titering once, while 266 (11.9%) were titered twice, 62 (2.8%) were titered three times, and 17 (0.8%) were titered at least four times. The mean age was 26.5 ± 6.5, and 2197 (98.2%) were male. A total of 69.5% of donors met ROLO donor criteria on the first test. The percentage of donors meeting universal-donor criteria increased to 83.5% on the second test, 91.1% on the third test, and 100% on the fourth and fifth tests. CONCLUSIONS: With successive titer testing, it appears that individuals display a tendency toward lower titers. This may indicate that titer testing may not be required after the second test if donors have been identified initially as low titer.

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.

The use of whole blood in US military operations in Iraq, Syria, and Afghanistan since the introduction of low-titer Type O whole blood: feasibility, acceptability, challenges.

BACKGROUND: Hemorrhage is the leading cause of preventable death in military and civilian traumatic injury. Blood product resuscitation improves survival. Low-titer Type O Whole Blood (LTOWB) was recently re-introduced to the combat theater as a universal resuscitation product for hemorrhagic shock. This study assessed the utilization patterns of LTOWB compared to warm fresh whole blood (WFWB) and blood component therapy (CT) in US Military Operations in Iraq/Syria and Afghanistan known as Operation Inherent Resolve (OIR) and Operation Freedom's Sentinel (OFS) respectively. We hypothesized LTOWB utilization would increase over time given its advantages. STUDY DESIGN AND METHODS: Using the Theater Medical Data Store, patients receiving blood products between January 2016 and December 2017 were identified. Product utilization ratios (PUR) for LTOWB, WFWB, and CT were compared across Area of Operations (AORs), medical treatment facilities (Role 2 vs. Role 3), and time. PUR was defined as number of blood products transfused/(number of blood products transfused + number of blood products wasted). RESULTS: The overall PUR for all blood products was 17.4%; the LTOWB PUR was 14.3%. Over the study period, the total number of blood products transfused increased 133%. Although the total whole blood (WB) increased from 2.1% to 6.6% of all products transfused, WFWB use remained at 2% while LTOWB transfusions increased from 0.5% to 4%. Transfusion of LTOWB occurred more in austere Role 2 facilities compared to Role 3 hospitals. CONCLUSIONS: LTOWB transfusion is feasible in austere, far-forward environments. Further investigation is needed regarding the safety, clinical outcomes, and drivers of LTOWB transfusions.