Clinical development of human polymerized hemoglobin as a blood substitute.

Abstract

Although the efficacy of hemoglobin-based oxygen carriers was established more than 60 years ago, all prior clinical trials have demonstrated significant toxicity characterized by renal dysfunction, gastrointestinal distress, and systemic vasoconstriction. The mechanisms of these toxicities now appear to be understood. Tetrameric forms of the hemoglobin molecule extravasate from the circulation and interact with endothelium-derived relaxing factor, leading to unopposed vasoconstriction. Although numerous efforts are under way to chemically modify the native tetramer, it is likely that all tetrameric forms of the hemoglobin molecule will continue to extravasate. We have focused on developing a polymerized form of hemoglobin that is virtually free of unreacted tetramer. The development and characterization of this polymerized pyridoxylated hemoglobin solution (Poly SFH-P) is described. Clinical trials have been completed successfully in volunteers and are now under way to assess the safety and efficacy of Poly SFH-P as a clinically useful red blood cell substitute for treatment of acute blood loss in the setting of trauma and surgery.

• Authors: S A Gould, G S Moss
• Journal: World journal of surgery (World J Surg) 1996 Nov-Dec Vol. 20 Issue 9 Pg. 1200-7 ISSN: 0364-2313 [Print] United States
• PMID: 8864082 (Publication Type: Journal Article, Review)

Chemical References

• Blood Substitutes
• Hemoglobins
• polyhemoglobin-pyridoxal-5-phosphate
• Pyridoxal Phosphate

Topics

• Animals
• Blood Substitutes (therapeutic use)
• Clinical Trials as Topic
• Exchange Transfusion, Whole Blood
• Hemoglobins (therapeutic use)
• Humans
• Pyridoxal Phosphate (analogs & derivatives, therapeutic use)
• Vasoconstriction (physiology)