The essay is an opinion piece written and submitted by the authors, who are military medical professionals, and edited by Task & Purpose editors. Task & Purpose welcomes submissions of opinion pieces on military medicine.
The Department of Defense must prioritize development and fielding of dried plasma for the treatment of severe bleeding on the battlefield.
Hemorrhage, or uncontrolled bleeding, is a leading cause of death on the battlefield.1-3 The overwhelming majority of these deaths occur at or near the point of need before reaching a Military Treatment Facility (deployed, forward-staged medical facility with surgical capabilities). Torso injuries, more commonly known as the chest, abdomen, and pelvis area, continue to be a leading cause of death prior to reaching surgical care. Treatment of these injuries is difficult in the prehospital setting with the currently available tools in the medic’s aid bag.
Currently, the only available tool for the medics to temporize this blood loss is the use of Tranexamic Acid (TXA) and forward-staged blood products, which are available in limited quantities and have significant logistical challenges associated with cold-chain storage requirements. With these limitations in mind, the Joint Force needs a shelf-stable resuscitative product for immediate use to bridge injured patients until other blood products, evacuation and advanced care are available.
Dried Plasma (freeze-dried or spray-dried) can temporarily stabilize casualties who require blood transfusion. Dried Plasma was used liberally during World War II by the US military.4 Since 2008 it has been pending Food and Drug Administration (FDA) approvals and clinical data to set conditions for more widespread use. The time is now to ensure that Dried Plasma becomes readily available for battlefield use. Dried Plasma confers logistical advantages and, in civilian trauma studies, plasma transfusion within 20 minutes of injury has demonstrated to improve survival.5 It is long overdue that combat casualties of today are afforded the same benefits of Dried Plasma that casualties did during WWII.
To do this, a concerted effort to accomplish the following is needed:
(1) Identify and support industry partners that are facile with the biologics development process and manufacturing, specifically with expertise in blood-product development
(2) Generate sufficient demand (military and civilian) for the product to justify the development cost associated with this process and be sustainable within the market
(3) Rapidly integrate the developed Dried Plasma into the medical supply chain
(4) Fund necessary research to optimize the integration of Dried Plasma into trauma care
Dried Plasma
Dried Plasma , or DP, was used extensively by the US military among expeditionary forces during World War II and Korea, both alone and in combination with whole blood. By the end of World War II, over 13 million pints of blood had been processed into 10 million units of Dried Plasma and 3 million into whole blood.4
Dried Plasma has several advantages over other blood products for the US military including relatively long shelf life, portability, and temperature stability. Once plasma is dried, it can typically remain on the shelf for one to two years and withstand fluctuations in temperature while still retaining desired functionality. The logistical benefits allow for more flexible use on a kinetic battlefield. While whole blood remains the optimal product, it carries relatively greater logistical challenges.
Although Dried Plasma was previously available in the US, it was removed from the US market in 1968 secondary to ‘plasma hepatitis’. During this time, hepatitis transmission was not fully understood, and the plasma was not tested for transmittable diseases.6 However, today’s risk of hepatitis from plasma transfusion is less than 1 in 100,000 units transfused secondary to drastically improved testing and hemovigilance protocols.
Dried Plasma use is international – France, Israel, Germany, and South Africa use freeze-dried plasma routinely.7 These countries have a robust manufacturing or purchasing capability, eliminating the supply/demand mismatch that often occurs with cold-stored blood products. Freeze-dried plasma from France (Centre de Transfusion Sanguine des Armées) was made available to the US Special Operations Command (USSOCOM) under an Investigational New Drug (IND) protocol from the Food and Drug Administration in 2011, then extended to the conventional military in 2018 under an Emergency Use Authorization (EUA).8
Use of the product under an EUA carries challenges, as it requires substantial additional documentation and tracking that would otherwise not be required under routine clinical care. Moreover, there is a significantly limited inventory available, and it is only available to medical personnel directly supporting USSOCOM and specific conventional military missions. As such, the use of the French freeze-dried plasma has been quite limited within the US military combat setting.8
In a study in South Africa, freeze-dried plasma is used in lieu of blood products when blood products are not available, with findings suggesting there is a potential role for freeze-dried plasma when blood products are lacking.7 A landmark study in the United States demonstrated that plasma transfused shortly after injury en route to the hospital in the setting resulted in a 30% reduction in death compared to no plasma, particularly with longer transport times to the hospital. Dried Plasma would likely confer the same reasonable survival benefit and thus Dried Plasma should be urgently adopted into US military and civilian trauma systems.5
Since 2008, the US military has actively supported the development of FDA-approved Dried Plasma product. In 2018, Congress, through Public Law 115-92, directed the Department of Defense and FDA to collaborate for more rapid authorization of medical products critical to the Joint Force and development of a Dried Plasma product has been prioritized under this framework. As recently as 2021, Teleflex submitted a Biologics License Application (BLA) to the FDA for a Dried Plasma product developed under a Cooperative Research and Development Agreement with the US military. Other manufacturers are also working towards Dried Plasma development and FDA authorization with US Government support. However, there are no other Dried Plasma products authorized for use in the US beyond the afore-mentioned French freeze-dried plasma EUA, at the time of this publication.
Current Blood Product Use
The current US military standard for resuscitation after hemorrhagic injury is bleeding control in accordance with Tactical Combat Casualty Care guidelines and early transfusion of LTOWB.9 Hemorrhage control and early whole blood transfusion are the standards of care that have evolved through data from US Central Command (CENTCOM), and early transfusion of whole blood has become a civilian standard as well. However, risks persist regarding supply-demand matches. Even during the recent relatively low casualty-generating conflicts in CENTCOM, the demand signal for blood products was more than the supply. Blood products to support all operational environments are procured through the Armed Services Blood Program (ASBP, URL: https://health.mil/Military-Health-Topics/Health-Readiness/ASBP). The ABSP was established in 1951 by President Truman when it was recognized at the beginning of the Korean War that the Armed Forces needed to maintain a blood program that could always supply wartime operations.
When not enough stored blood is available – the Walking Blood Bank (WBB), formally called an Emergency Donor Panel (EDP), is activated. In the EDP, prescreened donors (the ‘bank’) donate blood in real-time for the casualty in need.10,11 While the Emergency Dried Plasma is a good contingency and emergency plan, there is a risk in large-scale combat operations (LSCO) that: 1) the environment might be too kinetic to execute the WBB safely; 2) casualty numbers may exceed the blood available from WBBs; and 3) obtaining blood regularly from healthy warfighters may reduce combat end-strength due to decreased function among the donors and variable timeframes they are removed from strenuous activity.12 In these cases, Dried Plasma provides an immediate resuscitation capability while other blood products are being obtained from the WBB or the patient is moved to another facility with blood.
Since 2017, Flight Medics have commonly carried 1-2 units of lifesaving blood during air evac missions,13 but this is limited by both refrigeration requirements and size/weight/cube limitations as 2 units of blood weigh 1 kilogram plus the weight of the cooler. All Special Operations Combat Medics carry blood products during combat operations and this practice has slowly permeated into conventional ground forces, but the pace of implementation is slow. Moreover, blood products are carried infrequently during training operations. Furthermore, LTOWB is temperature sensitive (1-10° C/32-42° F), and depending on ambient temperatures, medics can likely keep the blood at an appropriate temperature for only 6-48 hours. The Military Services are working to increase the ability to carry blood products far forward on the battlefield with standardized equipment and training. However, the capability currently varies across the Joint Force and is often driven at the unit-level.
The current U.S military Joint planning factors for blood and blood products (Class VIIIB) is 20% of wounded in action (WIA) will require blood product therapy. Based on an extensive planning factor review in 2022, the Joint Staff Surgeon, Joint Trauma System, ASBP, and Services recommended eight (8) units of whole blood or whole blood equivalents are needed for those WIA that require transfusion.14 These products include whole blood, red blood cells, and fresh frozen plasma. During LSCO against a peer adversary, there is the potential for 1000 (or more) casualties a day. Based on the accepted planning factors: 200 of the WIA will each require eight (8) units of whole blood equivalents transfused in the first 24 hours, for a total of 1600 units. This blood supply will be difficult to achieve in an environment with contested logistics, thus, we have an urgent need to deliver temperature-stable, logistically feasible blood products to the battlefield that can act as ‘golden hour extenders.’ From donor eligibility and availability in theater to contested logistics, Army and joint medicine need more blood product capabilities far forward to save lives. We need blood products like Dried Plasma at or near the point of need and/or casualty collection point.
Time is a crucial factor in saving lives from bleeding. The greatest benefit of transfusion after injury is when it occurs rapidly; in patients with transport times longer than 20 minutes – prehospital transfusion is a lifesaving capability.5,15 This underscores the imperative to field Dried Plasma to operational environments that will have prolonged transport. Dried Plasma and LTOWB transfusion are necessary in LCSO to decrease death from survival injuries. As mentioned above, Dried Plasma has logistical advantages in contested, resource-constrained and highly kinetic environments.
To save lives on future battlefields, the DoD must continue to push for Dried Plasma fielding and continue to fund high quality research studies to compare transfusion strategy outcomes. During operations in Iraq and Afghanistan, over 350,000 blood products were transfused – close to 120,000 of those being plasma. In contrast, during WWII, over 10 million pints of blood were collected and processed into dried plasma.4 On day one of LSCO, to be truly ready to manage the large volume of anticipated casualties – the US military should have tens of thousands of Dried Plasma units in its armamentarium to save lives on the battlefield. The time to ensure this is a viable capability is now!
Civilian Benefit
This investment by the DoD into future combat casualty care would also support civilian trauma care. The silver lining of every war is the advancement of all trauma care. Prehospital practices that were unheard of before the recent conflicts, including limb tourniquets and whole blood, have revolutionized trauma care in the US. The number of estimated patients annually that would benefit from prehospital blood products ranges from 54,000 to 900,000.16 Currently, there are limited regions that carry blood products prehospital, with the areas that do demonstrate improved outcomes.17
While civilian data is not centrally collected among all hospitals, more than 800 designated trauma centers in the US participate in the Trauma Quality Improvement Program performance improvement registry.18 The Trauma Quality Improvement Program mandates blood volume reporting within the first 4 hours of hospitalization, with data from 2020-2022 demonstrating that over 414,000 units of plasma were transfused into trauma patients, and highlighting the civilian demand for dried plasma. Moreover, there is a dire civilian need for blood products outside of trauma, such as bleeding during childbirth and gastrointestinal bleeding.
Civilian EMS systems are currently constrained by several factors that would be completely sidestepped by the widespread use of dried plasma. The constraints center around three major factors: the ability to (1) procure the blood products, (2) store the products in compliance with temperature requirements, and (3) circulate the blood to other locations to avoid discarding blood that does not get used within the expiration date. The room temperature shelf-stability of Dried Plasma mitigates those challenges, making it nearly as simple as carrying tranexamic acid. The benefit of his DoD investment would extend far beyond that of the battlefield.
DISCLAIMER:The views expressed in this article are those of the authors and do not reflect the official policy or position of the U.S. Army Medical Department, Department of the Army, Department of Defense, or the U.S. Government.
Contact Information
Steven Schauer
X (Twitter): @armyemdoc
Instagram: @armyemdoc
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