Wu.qxp 6/3/08 12:44 Page 32
Transfusion
Current and Future Alternatives for Allogeneic Blood Product Transfusions
a report by
Christopher A Tormey,
1
Michelle L Erickson
1
and YanYun Wu
2
1. Fellow, Transfusion Medicine, Department of Laboratory Medicine, Yale-New Haven Hospital; 2. Assistant Professor, Department of Laboratory Medicine,
Yale University School of Medicine, and Assistant Director, Blood Bank and Apheresis/Transfusion Service, Yale-New Haven Hospital, Connecticut
The transfusion of allogeneic blood products is a complex medical As a result of the potentially harmful effects of blood transfusion, the
therapy relying on materials that are often available only in short finite supply of blood products and the routine refusal of transfusion by
supply and carry a number of substantial risks for the recipient. some groups, several alternatives to allogeneic transfusion therapy have
Perhaps the most feared complication of transfusion is the been created. In addition, continuous progress has been made in the
transmission of infectious diseases. Patients receiving blood products development of synthetic platelets and oxygen-carrying molecules, as
are potentially exposed to any number of micro-organisms, including well as recombinant coagulation factor concentrates and human-derived
bacteria, parasites and viruses, despite thorough testing.
1
Less well coagulation factor/complex concentrates, which provide maximal
known, but equally problematic, are the adverse events associated therapeutic benefit while substantially eliminating or reducing the risk of
with the infusion of blood products, which include severe lung injury, transfusion-transmitted diseases. This aim of this article is to review the
red blood cell (RBC) haemolysis and anaphylactic reactions.
2,3
current status of alternatives to allogeneic transfusions and to highlight
Blood transfusion should be reserved for those instances where new transfusion-related therapies.
it is indicated and no other alternatives exist. Furthermore, blood
products are often in high demand and shortages in RBCs, platelets Alternatives to Red Blood Cell Transfusion
and plasma can be problematic even in those cases where transfusion The development of synthetic alternatives to RBC transfusion has
is clinically appropriate. primarily focused on artificial carriers that are designed to deliver oxygen
to peripheral tissues. Currently, there are two broad categories of
In some cases, blood transfusion may not be an option even when oxygen carriers: perflurocarbons and haemoglobin-based oxygen carriers
clinically indicated. Prior to blood product transfusion, the risks and (HBOCs).
8,9
In addition to these options, there are several other
benefits must be explained and patient consent given. Adult patients alternatives to RBC transfusion, which are discussed under the ‘Peri-
have the right to refuse blood transfusions altogether for personal or operative Transfusion Alternatives’ section of this article.
religious reasons. For example, well known for their refusal of all blood
transfusions, with the possible exception of factor concentrates, are over Perflurocarbons
6.7 million practising Jehovah’s Witnesses.
4
While the courts are able to Perflurocarbons (PFCs) are emulsions suspended in an aqueous medium that
offer protection to children in their best interests if parents refuse absorb and release oxygen by diffusion. PFCs have been used in clinical
necessary treatment, transfusion to a non-consenting adult is considered settings to increase oxygen delivery, particularly during cardiac surgery.
8,9
A
an assault. For such patients, alternatives to blood transfusion are of significant drawback for PFCs is an inability to deliver large quantities of
paramount importance.
5–7
oxygen. At best, oxygen delivery capacity approaches 30% of normal
human whole blood. PFCs also have relatively long half-lives, with excretion
occurring over weeks to months after exposure.
8,9
Additionally, the
Christopher A Tormey is a Transfusion Medicine Fellow in the Department of Laboratory
Medicine at Yale-New Haven Hospital and the Yale University School of Medicine. He recently
administration of these synthetic carriers can result in myalgias, fever and
completed a residency in clinical pathology (laboratory medicine) at the Yale University School
transient thrombocytopenia.
8,9
Although recent developments, such as a
of Medicine. Dr Tormey received his medical degree from New York Medical College and an
PFC formulation consisting of microbubbles that can increase oxygen
undergraduate degree in chemistry from the University of Chicago.
delivery capacity to nearly 50% of that of whole blood, improvements are
E: Christopher.tormey@yale.edu
necessary before PFCs can be considered a blood substitute in the future.
8,9
Michelle L Erickson is a Transfusion Medicine Fellow in the Department of Laboratory Medicine
at Yale-New Haven Hospital and the Yale University School of Medicine. She recently
Haemoglobin-based Oxygen Carriers
completed residencies in anatomical pathology and clinical pathology (laboratory medicine) at
the Yale University School of Medicine. Dr Erickson received an undergraduate degree in
An HBOC is a purified haemoglobin compound stripped of its red cell
biology from Cornell University, her medical degree from the University at Buffalo School of stroma and reduced to the fundamental oxygen-carrying component.
Medicine and Biomedical Sciences and her business degree from the University at Buffalo
HBOCs are designed to increase oxygen-carrying capacity while reducing
School of Management.
the risks commonly associated with allogeneic RBC transfusion.
YanYun Wu is an Assistant Professor of Laboratory Medicine at the Yale University School of
Significant problems encountered in previous formulations of HBOCs
Medicine, where she also serves as Director of the Transfusion Medicine Fellowship Program. were recipient renal dysfunction, nausea and vomiting.
8,9
Recipient
She is also Assistant Director of the Blood Bank and Apheresis/Transfusion Service at Yale-
vasoconstriction, due to nitric oxide scavenging by free haemoglobin,
New Haven Hospital. Dr Wu received her medical degree from Beijing Medical University and
was another problem encountered with initial HBOC products.
8,9
her PhD from Tulane University. She completed both residency and fellowship training in
First-
clinical pathology (laboratory medicine) and transfusion medicine at the Yale University
generation HBOC use was also limited by the short circulating half-lives
School of Medicine.
of these molecules. As such, current approaches in HBOC engineering
have focused on modification of the haemoglobin molecule to increase
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