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American Journal of Therapeutics 2002This review article discusses the development and implementation of a number of blood substitutes, including hemoglobin-based oxygen carriers (HBOCs) and... (Review)
Review
This review article discusses the development and implementation of a number of blood substitutes, including hemoglobin-based oxygen carriers (HBOCs) and perfluorocarbons. This review article will introduce the reader to blood substitutes by discussing an overview of an ideal blood substitute, the history of HBOCs and perfluorocarbons, strategies of oxygen carrying, side effects of HBOCs and perfluorocarbons, current clinical trials, and the future of blood substitutes.
Topics: Animals; Blood Substitutes; Clinical Trials as Topic; Fluorocarbons; Humans
PubMed: 12237737
DOI: 10.1097/00045391-200209000-00012 -
Annales Chirurgiae Et Gynaecologiae 2001Despite increasing safety of blood supplies, and blood conservation strategies, the need for blood transfusion is increasing. Due to storage characteristics, blood is... (Review)
Review
BACKGROUND
Despite increasing safety of blood supplies, and blood conservation strategies, the need for blood transfusion is increasing. Due to storage characteristics, blood is not always available when it is needed.
AIMS
Review the necessity for an oxygen carrying blood substitute. Review the history of the compounds that may become blood substitutes, and briefly describe those in clinical trials.
MATERIAL AND METHODS
Review of literature in the area of blood substitutes.
RESULTS AND CONCLUSIONS
There is a need for oxygen carrying blood substitutes. Despite disappointments in recent clinical trials leading to withdraw of some compounds, there are several promising products nearing clinical approval.
Topics: Biological Transport; Blood Substitutes; Blood Transfusion; Fluorocarbons; Hemoglobins; Humans; Oxygen
PubMed: 11459262
DOI: No ID Found -
British Journal of Haematology Nov 2000
Review
Topics: Blood Preservation; Blood Substitutes; Costs and Cost Analysis; Erythrocyte Transfusion; Fluorocarbons; HIV Infections; Hemodilution; Hemoglobins; Hemorrhage; Humans; Military Medicine; Perfusion; Transfusion Reaction
PubMed: 11122077
DOI: 10.1046/j.1365-2141.2000.02326.x -
Artificial Cells, Blood Substitutes,... Jan 2000A novel series of perfluorocarbon (PFC) emulsions, based on perfluorodecalin (C10F18) and stabilised with up to 2.5% (w/v) of lecithin have been produced for evaluation... (Review)
Review
A novel series of perfluorocarbon (PFC) emulsions, based on perfluorodecalin (C10F18) and stabilised with up to 2.5% (w/v) of lecithin have been produced for evaluation as injectable, temporary respiratory gas-carrying blood substitutes. Some formulations contained 1.0% (w/v) of perfluorodimorpholinopropane (C11F22N2O2) to retard droplet growth through molecular diffusion (Ostwald Ripening). Other emulsions contained novel, amphiphilic fluorinated surfactants, such as, for example, the monocarbamate, C8F17C2H4NHC(O)(CH2CH2O)2Me (designated compound P6), at 0.1% (w/v) to enhance stability. Emulsions were prepared by homogenisation, were steam sterilisable and were stable for > 300 days (25 degrees C). Injection of rats (7.5 ml kg-1 b.w.) with emulsions produced significant (P < 0.05), transient increases in liver and spleen weights. One emulsion inhibited phorbol 12-myristate 13-acetate (PMA)-stimulated, Luminol-enhanced, chemiluminescence of human polymorphonuclear leucocytes (PMNL) in vitro, suggesting possible applications in ischaemic tissues for suppressing PMNL-mediated inflammation. The P6 fluoro-surfactant inhibited spontaneous platelet aggregation in hirudin-anticoagulated human blood in vitro, suggesting possible applications as an anti-thrombotic agent.
Topics: Adjuvants, Immunologic; Animals; Blood Substitutes; Drug Stability; Fluorocarbons; Humans; Platelet Aggregation Inhibitors
PubMed: 10676575
DOI: 10.3109/10731190009119783 -
Artificial Cells, Blood Substitutes,... 2006In this brief overview, recent progress and current status of blood substitute research and development is summarized. Current blood substitute development efforts are... (Review)
Review
In this brief overview, recent progress and current status of blood substitute research and development is summarized. Current blood substitute development efforts are focused on red blood cell substitutes but substitutes for platelets and other blood components are also in progress. Red cell substitutes currently in various stages of development are semi-synthetic or synthetic oxygen carriers that include "stealth" or "masked" red cells, hemoglobin-based oxygen carriers and perfluorocarbon-based oxygen carriers. Artificial platelets (or platelet substitutes) are in early stages of development and include human platelet fragments or particles of synthetic/semi-synthetic materials or recombinant human serum albumin coupled with platelet surface receptor fragments. Of note, some recombinant clotting factors (Factors VII, VIII, IX) have already been successfully developed and licensed for treatment of hemophilia. In addition, some future approaches and prospects of blood component replacement therapeutics are discussed.
Topics: Blood Coagulation Factors; Blood Substitutes; Hematopoietic Stem Cell Transplantation; Humans; Platelet Transfusion; Recombinant Proteins
PubMed: 17090427
DOI: 10.1080/10731190600973725 -
Transfusion Medicine Reviews Apr 1993Since our review 5 years ago, a new generation of PFC emulsion has been developed and is undergoing extensive testing. This new generation is the result of the... (Review)
Review
Since our review 5 years ago, a new generation of PFC emulsion has been developed and is undergoing extensive testing. This new generation is the result of the application of physicochemical principles, applied to both the choice of the PFC itself and the emulsifier, as well as advances in emulsion-producing technology. The efficacy of PFCs in general for oxygen transporting capability has been fully recognized, as exemplified by the limited license issued to Fluosol. The latter also represents the recognition of the relative absence of major toxicity of PFCs in general. The development of new products owes much to the lessons learned during the past 20 years and to advances made in the physical chemistry of PFCs. These advances now permit the rational selection or design of the most appropriate PFC and the design of emulsifiers best suited for the purpose. Perflubron represents a clear advance over the Fluosol-DA-type formulation. It is only one but the most advanced of the second-generation products. At least three other commercial entities (Hema-Gen/PFC, Green Cross, Adamantech) are also developing products based on the above principles. Five years ago we concluded that, in spite of the enormous complexity of PFC emulsions as large volume parenterals, they have shown remarkable biocompatibility. The advances in the past 5 years have confirmed this conclusion. The advances occurring during the past 5 years show that the application of the proper technology can lead to product improvement, and that PFC preparations with significant transfusional and nontransfusional potential are, in fact, feasible. It remains to be seen whether high PFC-content emulsion can be successfully deployed in initial, prehospital resuscitation situations. The high PFC content will reduce the absolute requirement for the maintenance of FIO2 > 0.8 in the case of Fluosol-DA for optimal efficacy. The second-generation products also seem to lend themselves to intraoperative use, because they can be removed from the blood postoperatively by plasmapheresislike methods. They are also suitable in combination with autologous blood donation/transfusion. All of these potential applications are in various stages of exploration and, if found to be efficacious, will likely conserve the supply of whole blood and blood components. The nontransfusional applications, particularly those in diagnostic imaging, seem to show substantial promise. Because they involve smaller doses than transfusional applications, they may enter clinical use earlier. The applications in radiation and chemotherapy of malignant diseases represent an intermediate position between the transfusional and nontransfusional uses.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Animals; Blood Substitutes; Fluorocarbons; Hemorrhage; Humans; Neoplasms; Oxygen
PubMed: 8481603
DOI: 10.1016/s0887-7963(93)70127-3 -
Artificial Organs Mar 2014
Topics: Blood Substitutes; Evaluation Studies as Topic; Humans
PubMed: 24606130
DOI: 10.1111/aor.12281 -
Trends in Biotechnology Sep 2014Here, we discuss recent advances in the development of artificial red blood cell (RBC) substitutes, illustrating lessons learned from initial attempts using... (Review)
Review
Here, we discuss recent advances in the development of artificial red blood cell (RBC) substitutes, illustrating lessons learned from initial attempts using perfluorocarbon (PFC) emulsions and acellular hemoglobin-based oxygen carriers (HBOCs). We also highlight novel oxygen-containing microparticles, nanoparticles, and stem cell-derived RBC products, with emphasis on improvements in biocompatibility and oxygen delivery. In addition, we envision future developments for the rational design of advanced blood substitutes that aim to address unmet clinical needs.
Topics: Biomedical Research; Blood Substitutes; Fluorocarbons; Humans; Nanoparticles; Oxygen; Stem Cells
PubMed: 24929580
DOI: 10.1016/j.tibtech.2014.05.001 -
Advanced Drug Delivery Reviews Feb 2000As an alternative to transfusion of red blood cells, intravenously (iv) administered artificial oxygen (O(2)) carriers are intended to increase the reduced O(2) carrying... (Review)
Review
As an alternative to transfusion of red blood cells, intravenously (iv) administered artificial oxygen (O(2)) carriers are intended to increase the reduced O(2) carrying capacity of blood in the case of acute severe anemia, i.e. hemorrhagic shock or extreme normovolemic hemodilution (ANH). Actually, two groups of artificial O(2) carriers are investigated: ultrapurified, stroma-free hemoglobin solutions (SFH) of human or bovine origin and synthetically produced perfluorocarbons (PFC). SFH may be administered in large amounts and are suitable for 1:1 replacement of blood losses in case of hemorrhage as well as for isovolemic exchange of blood during ANH. In both situations SFH solutions effectively restore (hemorrhagic shock) and maintain (extreme ANH) tissue oxygenation despite extremely low hematocrit values. The vasopressor property of the isolated Hb molecule leads to a species-dependent (rodent>pig>human) increase in systemic and pulmonary vascular resistance, but leaves overall distribution of cardiac output uninfluenced. Due to the particulate nature of PFC emulsions, iv administration has to be restricted to small doses (3-4.5 ml/kg body weight for the actually investigated 60% w/v perflubron emulsion) in order to avoid overload of the reticuloendothelial system. Thus PFC emulsions are unsuitable for isovolemic blood replacement in hemorrhagic shock or ANH. Low-dose iv PFC administration in already hemodiluted subjects, however, creates an additional margin of safety to guarantee adequate tissue oxygenation which allows for further, extreme ANH, without risking tissue hypoxia.
Topics: Animals; Blood Substitutes; Cattle; Humans; Oxygen; Oxygen Consumption; Perfusion
PubMed: 10837788
DOI: 10.1016/s0169-409x(99)00048-4 -
Artificial Cells, Blood Substitutes,... Jan 2001
Review
Topics: Blood Substitutes; Consumer Product Safety; Forecasting; Health Services Needs and Demand; Hemoglobins; Humans; Hypertension; Nitric Oxide
PubMed: 11280680
DOI: 10.1081/bio-100001251