What is efficacy of stroma-free hemoglobin as a blood substitute?

Updated: Dec 11, 2018
  • Author: Sara J Grethlein, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Stroma-free hemoglobin has been investigated as an oxygen carrier since the 1940s, when researchers realized that native hemoglobin is not antigeneic. A solution containing stroma-free hemoglobin has many advantages over red blood cells, including the ability to withstand sterilization and a shelf life of approximately 2 years at room temperature for some products.

Solutions of acellular hemoglobin are not as effective at oxygenation as packed red blood cells because of their high affinity for oxygen. Red blood cells have adapted to release oxygen at an oxygen half saturation pressure of hemoglobin (p-50) of approximately 26.5 mm Hg. This is due to the allosteric effect of 2,3-bisphosphoglycerate (2,3-BPG), which shifts the oxyhemoglobin dissociation curve to the right. In the absence of 2,3-BPG, stroma-free hemoglobin has a p-50 of 12-14 mm Hg.

Unmodified free hemoglobin, when infused rapidly, splits into dimers and is cleared by glomerular filtration and uptake by the reticuloendothelial system.

When free hemoglobin was used initially, it caused a substantial increase in oncotic pressure because of its hyperosmolarity. Unfortunately, the initial attempts at transfusing stroma-free hemoglobin produced renal dysfunction, coagulopathy, and hypertension. Adverse effects were attenuated by various modifications to the hemoglobin molecule to prevent glomerular filtration and to stabilize the molecule to withstand heat and chemical purification during production. Hypertension induced by infusion of these products was out of proportion to the volume infused and has been more difficult to prevent. It is thought to result from hemoglobin binding to nitric oxide, which is a potent vascular endothelial relaxant.

Several approaches have been tried to decrease the avidity with which hemoglobin binds to oxygen. These adaptations include the addition of organic phosphate to serve the function of 2,3-BPG and adenosine triphosphate, cross-linking dimers of hemoglobin tetramers and polymerizing the tetramers to decrease oncotic pressure and prevent glomerular filtration. Hypertension has remained a significant adverse effect of stroma-free hemoglobin.

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