A second approach to red cell substitutes which has been investigated is stroma free hemoglobin. This is produced by lysing red cells and releasing the hemoglobin. These preparations must be processed too remove all traces of the stroma and bacterial endotoxin. If this is not done, the stroma can cause severe renal damage. Even minute traces of endotoxin will cause a severe reaction in the recipient.

Free hemoglobin must be treated by one of several techniques to increase the dwell time in the body. Hemoglobin is a relatively small molecule which can be excreted across the kidney. To increase the dwell time in the body, the hemoglobin is either complexed to a larger molecule such as albumin or dextran, or chemically treated to cross link the molecules so the molecular size and weight is large enough to exceed the renal threshold.

Highly purified hemoglobin can also be prepared by recombinant cell cultures.

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