Blood substitutes as pharmacotherapies in clinical practice

Abstract

Polymerized hemoglobin preparations have proven 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.

Artificial oxygen carriers as a possible alternative to red cells in clinical practice

“…7 The quantity of gas dissolved is linearly related to its partial pressure and, when the partial pressure of arterial oxygen (pO 2 ) increases, the amount of oxygen carried by PFCs increases too. 4,6 Oxygen release to the tissues is almost complete when there is a high pO 2 gradient between arterial blood and the tissues. 7 High pO 2 is required to maximize the amount of oxygen transported.…”

“…4 PFCs do not have the oxygen-bonding properties of hemoglobin but act as simple solvents, and the transportation and release of gases are based on physical solubility. 6 Their oxygen kinetics are characterized by a linear relationship between partial pressure of arterial oxygen and oxygen content. 7 The quantity of gas dissolved is linearly related to its partial pressure and, when the partial pressure of arterial oxygen (pO 2 ) increases, the amount of oxygen carried by PFCs increases too.…”

“…6 The risks involved in transfusions include transmission of infections, delayed postoperative wound healing, transfusion reactions, transfusion-related acute lung injury, immunomodulation and the potential for cancer recurrence. [13][14][15] The incidence of transmission of the human immunodeficiency virus (HIV) by means of blood transfusions is around one in one million to one in 2.5 million units of blood, and the risk of hepatitis C is about one in 100,000 to one in 350,000 units.…”

“…These include preoperative autologous blood donation, preoperative use of erythropoietin, acute normovolemic hemodilution, perioperative blood salvage, pharmacological treatment (antifibrinolytic drugs, desmopressin and anti-inflammatory agents), hypotensive anesthesia, surgical techniques, acceptance of minimal hemoglobin levels and blood substitutes. 2,6 One attractive alternative to allogenic RBCs is synthetic blood substitutes, which can be applied independently of blood-group typing. 7 Currently, research on blood substitutes is centering on synthetically manufactured perfluorocarbons and hemoglobin solutions, i.e.…”

“…3 The ideal characteristics for blood substitutes are: nonantigenic properties; similarity to natural hemoglobin in terms of oxygen and carbon dioxide transport and delivery; absence of renal toxicity; stability at room temperature; sufficient half-life in circulation; long shelf life; ease of use; no overloading of the reticuloendothelial system; and low cost. [4][5][6] The development of modified hemoglobin solutions in the 1980s was an improvement, in which the products showed stability and fewer side effects. 5 Arterial oxygen carriers based on perfluorocarbons or hemoglobin-based oxygen carriers (HBOCs) are alternatives to allogenic red blood cells (RBCs).…”