Plasma is the liquid component of blood that contains thousands of proteins, growth factors, buffers, antibodies, hormones, and enzymes. There is abundant preclinical and clinical data to suggest that plasma can not only replace the lost blood volume, but is also protective for various cells and organs. Although plasma is extremely effective, it requires type and cross match, frozen storage, and thawing before administration, which makes it impractical for austere military settings. Many of these limitations can be overcome by converting the plasma into a freeze-dried, shelf-stable, easy-to-store preserved product, which performs as well as fresh frozen plasma in models of hemorrhage and traumatic brain injury (TBI) . Dried plasma can be kept in storage for years without losing efficacy and can be reconstituted easily in sterile water at the time of need (Fig. 49.3). Surprisingly, it is not a new technology. In fact, freeze-dried (or lyophilized) plasma was developed during the Second World War and was widely used. It fell out of favor in the 1970s due to concerns about the spread of hepatitis (and later HIV) as the product was made from plasma pooled from multiple donors. The current manufacturing technologies that use single-donor plasma and robust screening tools for communicable diseases make the freeze-dried product as safe as the commonly used fresh frozen plasma. Freeze-dried plasma products are approved for clinical use in Europe, and are being used by NATO troops in the current conflicts, including administration to US military personnel. However, they are not approved for use in the USA at this time. Prompt approval by the FDA would result in significant logistical benefits to the civilian trauma centers, as well as the US military forces.

Platelets with their limited shelf-life of up to 7 days storage at 20–24 °C represent a particularly challenging logistical problem for combat casualty care. Cryopreserved platelets (CPP) , stored in a special preservative solution, could reduce the logistic challenge as they could be stored for at least 2 years at −20 °C to −80 °C. CPPs have been studied in heart surgery patients and in cancer patients with extremely low platelet counts due to chemotherapy. CPPs are presently used in Europe, although the Food and Drug Administration has not yet licensed them for use in the USA.

In addition to plasma, lyophilized or freeze-dried platelets have also been created and studied. Freeze-dried platelets retain much of their native function and clotting capabilities, though other functions are lost during the current lyophilization process. They have a short duration of action and circulation time, suggesting that they can function more as an active and rapid hemostatic agent by forming primary hemostatic plugs and serving as a “scaffold” to support more long-term clot formation. Additional advances in the freeze-drying process may further improve and enhance the function of these platelets once they are reconstituted from the powder form. Taken together, these two advances in platelet storage have the potential to greatly expand the availability and longevity of platelet products, and to enhance the ability to carry platelets to even the most forward battlefield scenarios.

This exciting advance involves the production of blood cells outside of the human body to provide blood products that are safe, effective, readily available, and do not rely on human blood donors as a supply source. Theoretically, blood pharming could provide an alternative to red blood cell or platelet blood donation by producing large quantities of on-demand, universally compatible blood products free of risk for alloimmunization. This technology would utilize progenitor or “stem” cells that have the potential to differentiate into the desired cell type (red blood cell, platelet, etc.). These blood products would be produced in laboratory machines known as “bioreactors”, and could allow for controlled creation of the desired cell types and potentially even selective enhancement of their oxygen-carrying and hemostatic properties (Fig. 49.4). Because the blood products are grown in bioreactors, they could additionally be free of known and unknown infectious organisms. The Defense Advanced Research Projects Agency provided funding starting in 2007 to develop an automated culture and packaging system that would yield a fresh supply of transfusable red blood cells from readily available cell sources. While not yet clinically available, this technology has unlimited potential to revolutionize the creation and supply maintenance for blood products. In addition, these machines could also be scaled down and simplified so that they could become part of the standard equipment of a forward military treatment facility.

Soon after September 11, 2001, the US Department of Defense (DOD) funded intensive efforts to develop advanced hemostatic dressings. These collaborative efforts were extremely productive, and very rapidly a number of advanced hemostatic bandages/agents were developed, tested, and deployed. Since then, the original products have been further refined and many effective agents are now widely available. The current challenge is how to control bleeding in sites that are not within the reach of a bandage. These sites are typically within the chest or the abdominal cavity, and are now classified as “noncompressible truncal hemorrhage” (NCTH) . This is clearly the next frontier in hemorrhage control research, and many efforts are under way to develop agents that can control or stop NCTH. Some of the most promising include injectable self-expanding foam, vascular occlusive balloons, and special abdominal tourniquets. There is no one technology that would work in all anatomical locations, and most likely multiple complimentary methods will have to be developed and deployed in the future.