Thomas Mathis MS-3, AEMT, USAR MC‎
Abdul-Rahman Saleh MS-3, MLS‎
Kevin Le MS-3, EMT-B
Campbell University School of Osteopathic Medicine


Blood products are an essential component of trauma resuscitation. In the experience of ‎both the Afghan and Iraq Wars as well as that of operating rooms and emergency departments ‎throughout the country, timely administration of blood products has proven to decrease ‎morbidity and mortality in prehospital trauma victims suffering from hemorrhagic shock.1-2 The ‎benefit is so significant that civilian helicopter-based EMS programs routinely provide ‎prehospital transfusion to hemodynamically unstable trauma patients.3 The benefit of ‎concurrent hemorrhage control and blood product administration cannot be understated. ‎However, the practices surrounding prehospital blood products is still in its infancy, with ‎different agencies and organizations coming to vastly different conclusions as to its feasibility ‎and application. Through an organized review of the current literature, we provide a summary ‎of the contemporary trends related to prehospital transfusion practices and a window into the ‎future advances of both transfusion products and the trauma systems which incorporate them. ‎

The Past

Prehospital transfusion was first reported as early as the Franco-Prussian war of 1870 for ‎high-risk combat casualties, yet its modern use was only recently cemented with US military ‎combat casualties in the Afghan and Iraq Wars.4 The evolution of prehospital transfusion can be ‎tracked by the intervening conflicts that the United States has experienced. World War I and the ‎interwar years saw advances in blood typing and agglutination, but it wasn’t until World War II, ‎when plasma products were perfected, that medics and military physicians began regularly ‎administering plasma transfusions to battlefield trauma patients. The Korean War saw the role ‎of blood product transfusion diminish and the advent of balanced salt solution resuscitation as a ‎method for preventing post-traumatic renal failure.2,5 The influence of this transition still lingers ‎today, and it was not until the 1980’s that new emphasis was placed on hemostasis over ‎perfusion in a strategy that is commonly referred to as damage control resuscitation (DCR).5 ‎However, the use of crystalloids remains ubiquitous.‎

While the use of intravenous salt solutions might temporarily increase the intravascular ‎volume and blood pressure, there is no increase in the oxygen carrying capacity of the ‎hemocardiovascular system.6 Crystalloid infusion in traumatic shock causes dilutional ‎coagulopathy, anemia, endothelial damage, and tissue edema, leading to increased morbidity ‎and mortality. In 1994, Bickel et al. published a groundbreaking article in the New England ‎Journal of Medicine which showed delayed fluid resuscitation improved survival among ‎patients with penetrating torso trauma and reduced length of hospital stay.7 More recently, a ‎‎2014 meta-analysis found that mortality increased in patients with traumatic shock who ‎received liberal fluid resuscitation versus a restrictive fluid strategy.8 In 2015, a retrospective ‎analysis of 941 prehospital trauma patients found that those receiving more than one liter of ‎crystalloid fluid had a significantly increased likelihood of requiring transfusion in the ‎emergency department.9 ‎

Intensive study of its negative effects has instigated a steady decline in the role ‎crystalloids play in trauma resuscitation. Blood product transfusion has emerged as the gold ‎standard for volume replacement in DCR even in the prehospital setting, with the US Military’s ‎Committee on Tactical Combat Casualty Care (CoTCCC) recommending whole blood (WB) as ‎the fluid of choice in 2014. However, in subsequent years after that recommendation, the ‎CoTCCC found that 7% of all military prehospital trauma casualties continued to receive ‎crystalloid infusion compared with 2% receiving packed red blood cells (pRBCs) and 0.5% ‎receiving WB.2 Additionally, many studies pertaining to the influence of prehospital blood ‎products cite frequent crystalloid crossover of treatment groups as a persistent limiting factor. ‎As such, there continues to be a precipitous gap between the clinical ideal and the practical ‎application of prehospital blood transfusion. However, there is a growing movement within the ‎military and civilian community to close this disparity today. ‎

The Present ‎

In recent years, the trauma community has shown early transfusion of blood products to ‎be both safe and beneficial. Plasma, packed red blood cells (pRBCs), and platelets have all been ‎intensively scrutinized. In 2018, a study of helicopter-based prehospital plasma administration, ‎commonly referred to as the PAMPeR trial, demonstrated extensive reduction in 30-day ‎mortality for trauma victims comprising a wide array of morbidities, including prolonged ‎transport time, blunt force etiology, traumatic brain injury, and on-scene transfusion initiation.10 ‎Coincidentally, a competing 2018 study, known as the COMBAT trial, found that there was no ‎increase in transfusion related adverse events associated with plasma administration during ‎urban ground-based EMS transportation, but there was no significant survival benefit at 28-‎days.11 However, multiple post hoc combined analyses of both trials found increased 24-hour ‎and 28-day survival when study groups were controlled for age, injury severity and trial ‎cohorts.12 Plasma was shown not only to replace clotting factors themselves but also to stabilize ‎the endothelium and innate immune system, decreasing vascular leakage and edema. ‎

In addition to plasma, pRBCs are one of the most commonly employed blood products ‎in the field today. Eighty-four percent of French mobile emergency and resuscitation teams are ‎able to transfuse pRBCs in the prehospital setting. However, only 25.3% of US helicopter EMS ‎programs independently carry uncrossmatched blood as of 2016. Experience with pRBCs varies ‎from less than seven years to greater than 35 years amongst developed countries.13 Despite the ‎disparate experience and accessibility of pRBCs, it is safe and efficacious. In a systematic ‎review of prehospital pRBC transfusion, eleven separate civilian EMS studies reported no ‎transfusion reactions, but patients were more likely to be hypocalcemic and hypothermic upon ‎arrival. While a mortality benefit of pRBC administration was not consistently found in the ‎same review, six civilian studies and all military studies did show increased survival at various ‎time intervals, although not a single study analyzed was a randomized control trial.14‎

The last of the commonly utilized, prehospital blood products are platelets. The ‎transfusion of platelets achieves early hemostasis in a massive hemorrhage following a ‎substantial traumatic injury. In the US, the majority of platelets are stored at room temperature ‎in bulky storage agitators with constant agitation to prevent clotting. To fully utilize the ‎benefits of platelets in a timely manner with practicality, cold stored platelets (CSP) were ‎developed, which intrinsically has one unit of plasma for suspension. The major limitation ‎associated with CSP is shelf life since it expires in three days. CSPs are now being carried on ‎helicopters and administered to trauma victims in the prehospital setting, typified by trauma ‎center guidelines developed by the Mayo Clinic. In the prehospital transfusion setting, the CSP ‎unit is given after the administration of a pRBC unit. The administration of the CSP unit in ‎conjunction with pRBCs results in a 1:1:1 ratio of platelets, plasma, and pRBCs.15-16‎

The PROPPR trial, a 2015 hospital-based randomized control trial studying the ‎application of a 1:1:1 platelet, plasma, and pRBC transfusion ratio found that recipients had ‎similar survival rates and decreased propensity for exsanguination at 24 hours compared to a ‎‎1:1:2 ratio.17 This indirectly validates current transfusion practices in the prehospital setting. As ‎of 2017, the Mayo Clinic transfuses trauma patients on critical care transports with a 1:1:1 ratio, ‎starting with one unit each of cold stored platelets and pRBCs, and then subsequently ‎transfusing one unit of cold stored whole blood (WB). In both the dual unit and WB stages, the ‎combination of components achieves a 1:1:1 ratio of platelets, plasma, and pRBCs. Norwegian ‎helicopter EMS, instituting a national transfusion initiative in 2013, prefers a “plasma first” ‎methodology of freeze-dried plasma, pRBCs, and leukocyte reduced WB. In both the practices ‎of the Mayo Clinic and Norwegian HEMS, the most significant barriers to adoption and practice ‎have been storage capabilities and product wastage.15 Additional innovation is needed to ‎increase blood product adoption and improve the functionality of prehospital transfusion.‎

The Future

The Mayo Clinic’s WB strategy alludes to the ease with which plasma, platelets, and ‎pRBCs can be administered in a 1:1:1 ratio through a single transfusion product. The utilization ‎of whole blood provides a balanced resuscitation method with the ease of one bag and one ‎storage setting. Whole blood also offers the advantages of lower transfusion volume, ease of ‎administration, and exposure of the patient to only a single donor.18 ‎

The practicality and benefit of a low titer type O whole blood (LTOWB) transfusion ‎protocol has been trialed throughout the country with positive results. Since 2018, the ‎Southwest Texas Regional Advisory Council trauma service has performed LTOWB prehospital ‎transfusions in both urban and rural environments by air and ground transport. In retrospective ‎analysis, prehospital transfusions showed decreased incidence of massive transfusion events ‎compared to no prehospital transfusion. Additionally, patients receiving prehospital LTOWB ‎required less initial volume replacement. ED mortality was reduced and length of stay mortality ‎trended toward improvement.19 In a prospective, cluster randomized pilot study known as the ‎PPOWER trial, the University of Pittsburgh Medical Center demonstrated that prehospital ‎transfusion with LTOWB significantly lowered red cell component requirements at 6 hours and ‎‎24 hours. Additionally, prehospital LTOWB lowered K time and maximal amplitude ‎thromboelastography indices compared to pRBC prehospital transfusion. This study validated ‎the feasibility of a large, multicenter prospective trial of LTOWB in the future.20‎

While storage of cold stored blood products serves as one of the major challenges ‎associated with prehospital transfusions, the Norwegian emergency medical service has ‎demonstrated the practicality of freeze-dried plasma (FDP). FDP stored at room temperature is ‎dissolved in 200-300 ml of sterile water and is ready to be injected in three to six minutes. FDP ‎has been assessed safe to use with over 500,000 units of FDP transfused without any reported ‎side effects.15 FDP also provides the same neuroprotection as compared to fresh plasma in ‎animal surgical models of TBI.21 The Israeli Defense Force (IDF) Medical Corps instituted a ‎strategic plan in 2012 that designated FDP as the resuscitation fluid of choice in the prehospital ‎setting. The IDF found in a retrospective analysis of casualties from 2013 to 2016 that FDP ‎improved INR and fibrinogen levels, but failed to show meaningful benefit in hemoglobin or ‎platelet levels.21 Similarly, a study of IDF storage practices found that under field conditions ‎there was negligible degradation of FDP clotting factors at twelve months.22 Representing its ‎potential for civilian EMS, a single center, retrospective analysis of FDP use in Southeast ‎England helicopter evacuations demonstrated quicker transfusion initiation times and lower ‎pRBC volumes needed in treatment of critical trauma patients.23 Globally, FDP is considered ‎safe and effective with many advanced organizations adopting its use, but multicenter, ‎randomized control trials are still needed to validate these claims. ‎


Blood product transfusion, coupled with prompt control of compressible hemorrhage, is ‎the greatest intervention currently available to prehospital providers to decrease morbidity and ‎mortality in trauma patients. However, the transfusion of blood products in the prehospital ‎setting in a timely manner includes multiple practical challenges particularly with limited ‎resources and personnel. Yet, the establishment of prehospital transfusion criteria is crucial and ‎lifesaving. Various observational studies highlight improvement in care and mortality with the ‎utilization of prehospital, blood product transfusion, but few randomized control trials have ‎been able to illustrate the benefits definitively. Whole blood and freeze-dried plasma offer ‎perhaps the greatest promise in providing this resuscitation modality to the greatest number and ‎diversity of EMS organizations. Concerted efforts should be made not only to prove these ‎products’ validity through prospective study, but also to innovate new methods for ‎incorporating them into the standard logistics of prehospital services. ‎


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