Oxidative Hemolysis and Precipitation

The propensity of certain chemicals and drugs to induce hemolytic anemias has been a subject of much interest for almost a century (1-4). The majority of substances so active are aromatic compounds containing amino-, nitro-, or hydroxy groups, although a number of inorganic compounds (e.g., hydroxylamines, nitrates, nitrites and chlorates) are also active (1-4). Such compounds usually cause red cell injury without evidence of specific toxicity to other cells or tissues. The hemolytic process is characterized by two rather distinctive features in the affected red cells: 1) the appearance of l)rownish or greenish derivatives of hemoglobin, including methemoglobin, according to most (3) but not all (4) reports; and 2) the formation within red cells of water-insoluble, stainable granules, generally termed Heinz bodies. There has been extensive debate as to the identity and significance of the hemoglobin discoloration following the adiministration of these compounds. Much of the disagreement may be attributed to the fact that many of the observations have been made in vivo, where pigments initially produced by the compound are mixed with the various products of hemoglobin catabolism. Furthermore, the fact that certain of the pigments produced, such as miiethemoglobin, are reversible, whereas certain others (including so-called sulfhemoglobin) are not (3), has undoubtedly led to conflicting observations. In those few studies where early, sequential observations have been made, methemoglobinemia has been striking albeit transient (5, 6). Studies of compounds such as phenylhydrazine, which are active against red cells in vitro as well as in vivo, have shown that hemoglobin may be changed in part to methemo-