Page 68 - JSOM Fall 2023

TABLE 3 Developmental Stages of Red Blood Cell and Platelet Replacement Products
Product Name Type Source Action Clinical Trials Approval
Hemotech 18 Cross-linked and Bovine hemoglobin Oxygen carrier Preclinical and initial None
surface-modified– conjugated with ATP, clinical trials undertaken
HBOC adenosine, and reduced outside U.S.
glutathione
Hemospan Surface-modified– Oxygenated polyethylene Oxygen carrier Phase III clinical trials in None
(MP4OX) 19 HBOC glycol-modified human U.S. complete
hemoglobin
Hemopure Cross-linked and Bovine hemoglobin Oxygen carrier Expanded access Approved in South
(HBOC-201) 20– 23 polymerized HBOC (compassionate use) and Africa and Russia
investigation new drug
trials underway to treat
anemia
Oxyglobin Cross-linked and Bovine hemoglobin Oxygen carrier Canine anemia trials were Approved for
(HBOC-301) 24,31 polymerized HBOC completed in late 1990s veterinary use
PolyHeme ®25,26 Cross-linked and Glutaraldehyde, human Oxygen carrier Phase III clinical trials in None
polymerized HBOC hemoglobin U.S. ongoing
Diaspirin Cross-linked HBOC Human hemoglobin Oxygen carrier Phase III clinical trial in None
(DCLHb) 27,28 U.S. complete
ErythroMer 29,30 Cross-linked, Amphiphilic Oxygen carrier Animal testing only None
polymeric polymerization of
nanoparticle HBOC hemoglobin using
polyethylene imine
OxyBridge HBOC: Hyperpolymerized Oxygen carrier Animal testing only None
™
(VIR-HBOC) 32,33 Surface-modified–, human hemoglobin
cross-linked LEH
Perftoran ® PFOC Perfluorocarbon Oxygen carrier Outside U.S. only Approved in Russia
(Vidaphor) 35 emulsion in a surfactant and Mexico for
and electrolyte solution hemorrhagic shock
Oxycyte 36–38 PFOC Perfluorocarbon-based Oxygen carrier Phase II clinical trials for None
oxygen carrier treating traumatic brain
injury completed in U.S.,
Israel, and Switzerland
Oxygent 39 PFOC Emulsion of Oxygen and Phase II trials to determine None
perfluorooctyl bromide CO carrier oxygen-carrying capacity in
2
non-traumatic respiratory-
compromised patients
PHER-O2 40 PFOC Perfluorocarbon-based Oxygen carrier Preclinical trials ongoing None
oxygen carrier
Fluosol-DA 41 PFOC Perfluorocarbon emulsion Oxygen and Phase III clinical trials in FDA approved in
CO carrier U.S. complete 1989 and removed
2
from market in 1994
SynthoPlate 50 Platelet Liposome with integral Hemostatic agent Animal testing only None
vWF and collagen-
binding peptides
PlateletBio 51–53 Platelet Platelet-like cells Platelet Novel research None
replacement and
hemostatic agent
ATP = adenosine triphosphate; HBOC = hemoglobin oxygen carrier; LEH = liposome-encapsulated HBOC; PFOC = perfluorocarbon-based
artificial oxygen carrier; vWF = von Willebrand factor

Platelet Replacements Two platelet substitutes in development are SynthoPlate
Platelets are essential elements of blood that are responsible (Haima Therapeutics) and PlateletBio (PlateletBio). Syntho-
for coagulation. However, their broader roles include im- Plate is a hemostatic agent that is generated as a liposome with
munologic responses, angiogenesis, tissue regeneration, and integral von Willebrand factor and collagen-binding peptides.
wound healing. Physical, spatial, and temporal factors influ- In murine and porcine studies, it has reduced life- threatening
ence different populations of platelets. Therefore, the in vitro hemorrhage and prevented exsanguination. In a much ear-
50
production of platelets could allow these different functions to lier stage of development, PlateletBio consists of artificial
be tailored for specific uses. In response to injury and trauma, platelet-like cells specifically designed to replace platelets and
platelets that produce stromal cell-derived factor 1 (SDF-1), a act as a hemostatic agent. 51–53
CXC chemokine that binds to the CXCR4 receptor, have been
shown to promote the recruitment of endothelial progenitor Blood Product Comparison
48
cells to arterial thrombi in vivo. Researchers have recently
generated platelets in vitro in a novel microfluidic system, RBC replacements are leading the artificial blood race, and
demonstrating the formation of a significant number of func- one HBOC (Hemopure) is FDA-approved for compassionate
tional platelets from their precursor, megakaryocytes. 49 use. However, unencapsulated HBOCs might not be the ideal

66 | JSOM Volume 22, Edition 3 / Fall 2023