Page 65 - JSOM Fall 2023

Artificial Blood Development

Implications for Military Medicine

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Vanessa R. Melanson, PhD ; Jeremy R. Hershfield, PhD *; Michael Kevin Deegan ;
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Hyeveen Cho ; Dion Perinon ; Stacey L. Bateman ; Jason Barnhill, PhD 7
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ABSTRACT
Massive hemorrhaging remains the most common cause of individual blood components. We also provide an overview of
preventable battlefield deaths. Blood used for trauma care several artificial blood products that could eventually be used
requires a robust donation network, capacity for long-term for hemorrhagic management at the point of care.
storage, and extensive and accurate testing. Bioengineering
technologies could offer a remedy to these constraints in the Human Blood Composition
form of blood substitutes—fluids that could be transfused
into patients to provide oxygen, carry away waste, and aid A brief description of the components of blood is necessary
in coagulation—that would be used in prolonged casualty to review its wide array of functions, as well as to better ap-
care and in far-forward settings, overcoming the obstacles of preciate blood’s complexity with respect to its artificial man-
distance and time. The different molecular properties of red ufacture. Blood is a complex fluid composed of cellular and
blood cells (RBCs), blood substitutes, and platelet replace- acellular components that are essential for human life. In ad-
ments contribute to their respective utilities, and each type is dition to oxygen delivery, blood is responsible for waste re-
currently represented in ongoing clinical trials. Hemoglobin moval, nutrient delivery, and the maintenance of fluid balance
oxygen carriers (HBOCs) are the most advanced RBC replace- in tissues, with important roles in the lymphatic, immune, and
ments, many of which are currently being evaluated in clinical digestive systems (Table 1). Blood’s myriad functions result
trials in the United States and other countries. Despite recent from its complex components: erythrocytes (RBCs), leukocytes
advancements, challenges remaining in the development of (white blood cells [WBCs]), and platelets. RBCs are integral to
blood alternatives include stability, oxygen capacity, and com- oxygen transport and are essentially transport vessels for he-
patibility. The continued research and investment in new tech- moglobin, the protein that delivers oxygen to tissues from the
nologies has the potential to significantly benefit the treatment lungs. WBCs are components of the immune system, compris-
of life-threatening emergency injuries, both on the battlefield ing various cell types that fight infection. WBCs include im-
and in the civilian sector. In this review, we discuss military mune response–mediating T and B lymphocytes, bactericidal
blood-management practices and military-specific uses of in- neutrophils, natural killer cells that limit the spread of dam-
dividual blood components, as well as describe and analyze aged cells and cells infected by pathogens, parasite-fighting eo-
several artificial blood products that could be options for fu- sinophils, and allergen-response–initiating basophils. Platelets
ture battlefield use. are cellular fragments vital to blood coagulation in response to
blood vessel injury. Acellular components of blood are essen-
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Keywords: artificial blood; blood substitutes; red blood cell tial for maintaining homeostasis. Electrolytes such as sodium,
substitutes; platelet replacements; biomanufacturing potassium, chlorine, and bicarbonate regulate osmotic pres-
sure and are vital in nerve excitation, muscle contractions, and
cell metabolism. Various proteins such as albumin, insulin, and
antibodies regulate fluid balance, act as signaling hormones,
Introduction
or defend the body from infection, respectively. Inactive mole-
Massive hemorrhaging has been the foremost cause of pre- cules—for instance, fibrinogen and prothrombin—respond to
ventable deaths for Warfighters for centuries, and the recent specific signals and aid in the coagulation cascade when the
combination of improvised explosive devices, increased caliber body suffers trauma. 4
weaponry, and armor-piercing munitions has led to a higher
incidence of hemorrhagic wounds since the 1990s. The cur- Blood Management in the Military
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rent battlefield standard of care is to preferentially provide
cold-stored low-titer O whole blood that is predominantly The military healthcare system is self-contained, encompass-
collected at military and federal installations. However, this ing all aspects of the distribution, storage, and transfusion of
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strategy depends on blood donations and a reliable cold- collected blood. The Armed Services Blood Program collects
chain transport process. In this review, we examine military whole blood and produces apheresis products (e.g., RBCs,
blood-management practices and the military-specific uses of plasma, platelets) at many military and federal installations
*Correspondence to jeremy.hershfield@westpoint.edu
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1 Dr Vanessa R. Melanson, Dr Jeremy R. Hershfield, 2LT Michael Kevin Deegan, 2LT Hyeveen Cho, 2LT Dion Perinon, and MAJ Stacey L.
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Bateman are affiliated with the Department of Chemistry and Life Science, United States Military Academy, West Point, NY. COL Jason Barnhill
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is affiliated with the Department of Chemistry and Life Science, United States Military Academy, West Point, NY, and with the Department of
Radiology, Uniformed Services University of the Health Sciences, Bethesda, MD.
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