الفهرس 
PHYSIOLOGICAL BASISOnly 14 pages are availabe for public view
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Abstract
Allogeneic blood transfusions have been associated with several risks and complications and with worse outcomes in a substantial number of patient populations and clinical scenarios. Allogeneic blood is costly and difficult to collect, transport, and store. Global and local shortages are imminent. Alternatives to transfusion provide many advantages, and their use is likely to improve outcomes as safer and more effective agents are developed.
Current demands over the blood supply in developed and developing nations will compound over time. Red cell substitutes have a promising value proposition for transfusion services, because they hold the promise of increasing the availability of blood products and removing donor and contamination safety risks. On the other hand, existing products suffer from critical shortcomings such as vasoactivity; but it should also pointed out that substitutes not based on human blood introduce potentially more complex safety hazards.
Current efforts are have been made to develop hemoglobin-based oxygen carriers as blood substitutes in light of the worldwide shortage of
safe and viable allogeneic donor blood. There are now viable approaches
to modify the intrinsic biologic properties of hemoglobin to produce improved hemoglobin-based oxygen carriers. Polymerized hemoglobin
preparations have proved most successful in clinical trials due to their improved side effect profile. The goal is to evaluate blood substitutes with enhanced intravascular retention, reduced osmotic activity, and attenuated hemodynamic derangements such as vasoconstriction. Although not without substantial morbidity and mortality, the current safety of allogeneic blood transfusion demands that comparative studies show minimal adverse effects as well as efficacy and potential for novel applications.
Since the inception of allogeneic blood transfusion, the search for an alternative to the use of stored packed red blood cells has been underway. Over the last 10 years, modified hemoglobin solutions in the form of hemoglobin-based oxygen carriers (HBOCs) have made significant strides toward becoming clinically available and useful. Although HBOCs are not yet ready for regular use in the clinical arena, this may change in the near future as HBOC products continue to improve and as the elucidation of the mechanisms of any adverse effects becomes clearer.
Hemoglobin-based oxygen carriers (HBOCs) were initially developed to provide an alternative to blood transfusion. With the realization that hemoglobin solutions not only are red blood cell substitutes but also have a number of additional properties, including hemodynamic effects related to their oncotic and nitric oxide–scavenging effects, the broader concept of ‘‘hemoglobin therapeutics’’ was born. Promising effects on oxygen transport and the microcirculation need to be confirmed, and the results of studies with newer, second-generation HBOCs are eagerly awaited. In the meantime, possible adverse effects need to be carefully evaluated before HBOCs can be widely used in the ICU, emergency room, or prehospital setting.
Human polymerized hemoglobin (PolyHeme) is a universally compatible oxygen carrier developed for use when red blood cells are unavailable and oxygen-carrying replacement is needed to treat life-threatening anemia. The benefit-to-risk ratio of PolyHeme is favorable when blood is needed but is not available or an option.
Molecular biology has been applied to the development of hemoglobin based oxygen carrier (HBOC) proteins that can be expressed in bacteria or yeast. Cross-linked polymers of recombinant hemoglobin have the characteristics of molecular size, molecular stability, and oxygen delivery to hypoxic tissue suitable for an HBOC.