Abstracts from the First International Sickle Cell Anaemia Conference

Errors occurred in publication of two of the abstracts from the First International Sickle Cell Anaemia Conference (BLOOD 34:727-737, November 1969). On page 733, the abstract "The Irreversibly Sickled Cell" listed authorship incorrectly, and in the second column of that page (733), the paragraph beginning "Androgens stimulate erythropoiesis," should have been preceded by title and author lines as a new abstract. The abstracts are repeated below in their correct form:

THE IRREVERSIBLY SICKLED CELL. John F. Bertles.

Sickle-cell anemia (Hb SS disease) provides opportunities to study in man the significance of a variability from cell to cell in the relative proportions of similar proteins which coexist within individual members of a cell population. Work from this laboratory has shown that net synthesis of fetal hemogloblin (Hb F) is least in erythroid precursors destined to become irreversibly sickled cells (ISC), and that these morphologically obvious deviants suffer preferential destruction. Cell content of total hemoglobin is constant from cell to cell: hence absolute amounts of Hb S and Mb F vary reciprocally within any one Hb SS cell population.

Structural deformation of erythrocyte membranes by a filamentous alignment of deoxygenated Hb S molecules is presumably responsible for reversible sickling, but hemoglobin within ISC can be either filamentous (sickled) or structureless (non-sickled). Further definition of ISC and non-ISC by transmission electron microscopy has revealed an aberrant appearance of ISC membranes suggesting structural damage. A characteristically tight longitudinal ordering of filaments in deoxygenated ISC probably mimics filament arrangement during postulated periods of sequestration which led to irreversible cell distortion.

It appears likely from these studies that low net synthesis of Hb F during early maturation of an erythroid precursor is responsible for this ultimate chain of events: (a) facilitated sickling; (b) increased tendency to sequestration; (c) membrane damage and consequent irreversible deformation; and (d) cell death.

ANDROCEN THEORY AND SICKLE CELL ANEMIA, William C. Mentzer, Charles S. August, and David G. Nathan.

Androgens stimulate erythropoiesis; in sickle hemoglobin syndromes an additional effect—inhibition of sickling—has recently been proposed. We treated 2 female SS disease patients with IM testosterone enanthate for 2-3 months and observed an elevation of 255 cc. and 460 cc. in their respective total RBC volumes with a concomitant rise in hemoglobin concentration. Work capacity (measured by ergometry) and sense of well being improved. Therapy did not alter the ⁵¹Cr RBC life span or the sickling proclivities of the patient’s erythrocytes. The latter was assessed by enumeration of irreversibly sickled cells, by the Na metabisulfite test, and by studies of K+ loss from ouabainized RBC exposed to varying O₂ tensions. Total fetal hemoglobin, synthesis of gamma chains by reticulocytes, and the usual heterogeneous distribution of Hb F in erythrocytes were unchanged by therapy. Whole blood vicosity, measured in a rotational viscometer, and RBC deformability, measured by a millipore filtration, were unimproved. A third patient, a male treated with oral oxymethalone, experienced the expected rise in total red cell volume. Unlike our previous patients, his RBC lifespan (⁵¹Cr) was slightly lengthened by therapy and his irreversibly sickled cells fell from 35 per cent to 5 per cent. Fetal hemoglobin and viscosity were not altered by therapy. In this patient, androgens may have influenced the sickling phenomenon but if so the mechanism remains obscure.

Complications of androgen therapy include fluid retention and priapism which led to cessation of therapy after 2 weeks in an 8 year old male. Reversible virilization of females was also observed.

Further study of the effect of androgens in sickle cell syndromes with particular reference to possible effects on the rate of sickling are in progress.