1. By exposing hemoglobin solutions to an alkaline reagent at a pH of 12.7 it was found that normal pigment is completely denatured within one minute. Thus even small amounts of more resistant hemoglobins, which may also be present in the solution, can be readily detected. Fetal hemoglobin, which is alkali resistant, may remain demonstrable until the end of the second year of life. 2. Alkali resistant hemoglobins were regularly encountered in sickle cell anemia (but not in the trait), in the more fully developed Mediterranean syndromes, and in 1 out of 4 families with hereditary spherocytosis. In addition to these hereditary hemolytic disorders, abnormally denaturing hemoglobin fractions were observed in 3 instances of chronic aregenerative anemia, and, irregularly, in patients with untreated pernicious anemia, acute and chronic leukemia and myelophthisic anemia. All other kinds of anemias were found to have only normally denaturing pigments. 3. Three definite types of hemoglobin are identifiable at present by means of electrophoresis and denaturation. These have been designated as type N (normal adult), type F (fetal), and type S (sickle cell hemoglobin). The hypothesis is advanced that the resistant fraction in the hereditary hemolytic syndromes may represent a continued production of fetal pigment beyond the physiologic age limit and the appearance of the abnormal hemoglobins in the "acquired" disorders may indicate a reactivation of such a mechanism. The implications of such an assumption for the distribution of the various types of hemoglobin in sickling erythrocytes are discussed. 4. The diagnostic significance of the denaturation test and its limitations are outlined.
The results of starch block electrophoresis of normal adult hemoglobin in the various disease states has been reported. The slow-moving fraction, A2, is elevated in all patients so far studied with thalassemia. Some patients with Addisonian pernicious anemia also show an increase in this fraction. Cord blood contains very little A2. The A2 fraction has no correlation with the severity of the disease. The A2 fraction found on starch seems to be identical with the small, fast-moving component noted in the Tiselius apparatus at acid pH. Iron deficiency anemia of the acquired type tends to have a lower amount of A2 than normal, with an increase to average normal values after therapy.
By means of fractional denaturation, it is possible to follow the progress of alkaline degradation of resistant hemoglobins. A characteristic pattern was established for the fetal compound. The alkali resistant hemoglobin fractions in Mediterranean anemia and in some acquired hematologic conditions (acute leukemia and chronic aregenerative anemia) behaved like the fetal pigment. In sickle cell anemia only 4 out of 11 specimens were found to have fetal hemoglobin, whereas the others seem to have a fetal-like compound. Similarly, in 2 members of one family with hereditary spherocytosis, the resistant pigment was also fetal-like. The significance of these findings for the hypothesis that the resistant hemoglobin fractions in these disorders represent either a continuation or a reactivation of the production of the embryonic pigment is discussed.
(1) Four Negro patients with mild sickle cell-thalassemia disease (heterozygous for the genes for S hemoglobin and for thalassemia) are described. In contrast to reports in the literature, some of these patients are only mildly anemic, or not anemic at all. In three, the values for MCV and MCH are decreased, but in one, all hematologic indices are normal. All four individuals show leptocytosis and elevated reticulocyte levels. (2) Hemoglobin analyses, consisting of a combination of electrophoresis and the alkali denaturation technic, demonstrate the S + A + F pattern in three, and the S + A pattern in the fourth. These patterns are considered pathognomonic for sickle cell-thalassemia disease. They may be sharply differentiated from the S + F pattern, encountered in classical (homozygous) sickle cell anemia, and from the A + S pattern found in the heterozygous sickle cell trait. The various types of hemoglobin are reported in the sequence of their quantitative representation in the hemolysate. Hemoglobin analysis is indispensable for the recognition of the different types of sickle cell disease. (3) Evidence is cited that clinically almost asymptomatic sickle cell-thalassemia disease is probably not too rare in the American Negro population. (4) The genetic aspects of the production of fetal hemoglobin are discussed. It is postulated that the production of fetal hemoglobin is also under genetic control. The genes for fetal hemoglobin are not alleles of the genes for normal adult hemoglobin and are physiologically almost completely suppressed by the latter. Pathologic genes may render this suppression incomplete.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.