What is the efficacy of polymerized hemoglobin blood substitutes?

Updated: Dec 11, 2018
  • Author: Sara J Grethlein, MD; Chief Editor: Emmanuel C Besa, MD  more...
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The development of polymerized hemoglobin was also a result of significant adverse effects caused by intravenous infusion of stroma-free hemoglobin. The cross-linking agent in this case was glutaraldehyde. However, it was discovered that the Hb-glutaraldehyde polymerization reaction was difficult to control and resulted in the formation of products of various molecular sizes.

PolyHeme (Northfield Laboratories Inc., Evanston, Ill) is a first-generation pyridoxylated polymerized hemoglobin made from outdated human blood. It is one of the few products currently being evaluated in a phase III clinical trial that is enrolling patients. It has a half-life of 24 hours, a shelf life longer than 12 months when refrigerated, and a p-50 of 28-30 mm Hg. In a phase II trial in 44 patients with acute trauma, PolyHeme reduced the required the number of allogenic red blood cell transfusions. Results of a trial published in 2002 showed that 75% of patients with red cell hemoglobin levels less than 1 gm% survived traumatic injury after receiving PolyHeme as compared to 16% of historical controls at the same hemoglobin level. [8]

Northfield laboratories was involved in a 720-patient phase III trial in trauma patients in which subjects were randomized to receive either PolyHeme or standard of care at the time of injury. On reaching the hospital, patients in the control arm receive blood as indicated whereas patient in the PolyHeme arm continued to receive PolyHeme for 12 hours, and then received blood, as indicated. Preliminary results indicated that 46 of 349 patients treated with PolyHeme died, whereas 35 of 363 patients in the control group died. The difference in mortality between the 2 groups at 30 days was not significant. Therefore, the trial seemed to show that although PolyHeme was not inferior to standard of care, it was not superior to it either.

Other first-generation polymerized hemoglobin products include HbOC-201 [9] (Hemopure manufactured by Biopure Corporation, Cambridge, Mass) and HemoLink (Hemosol Corporation, Mississauga, Canada).

Hemopure is a polymerized form of bovine hemoglobin with a p-50 of 30 mm Hg that is closer to human hemoglobin than stroma-free hemoglobin. It has an intravascular half-life of 8-23 hours and a shelf life of 36 months at room temperature. Hemopure is approved in South Africa for the treatment of adult surgical patients who are acutely anemic with the intention of eliminating or reducing the need for allogenic red blood cell transfusions. In the United States, phase II trials have been put on hold due to safety issues.

In December 2006, the Blood Products Advisory Committee of the FDA voted against recommending that the US Navy proceed with late-phase clinical trials of Hemopure. The main reason for this was the adverse effect profile of this compound since previous studies had shown that Hemopure could increase the risk of strokes and myocardial infarction. Biopure is currently addressing the FDA's questions regarding safety and efficacy of the product.

A comparative study of HBOC-201 versus allogeneic red blood cell (RBC) transfusions found that up to 7 units of HBOC-201 infused over the course of 6 days resulted in RBC transfusion avoidance in 43% of patients. [10, 11]

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