The Turnover of Hemoglobins A, F, and A2 in the Peripheral Blood of Three Patients With Thalassemia*

Influence of hemoglobin precipitation on erythrocyte metabolism in alpha and beta thalassemia

“…The erythrocytes of patients with beta thalassemia and hemoglobin H disease can be separated by centrifugation into young and old cohorts (1)(2)(3)(4). In beta thalassemia the young cells contain less hemoglobin F (2,3) and, if the patient is splenectomized, more insoluble membrane-bound inclusions of precipitated alpha chains (4)(5)(6)(7).…”

“…In beta thalassemia the young cells contain less hemoglobin F (2,3) and, if the patient is splenectomized, more insoluble membrane-bound inclusions of precipitated alpha chains (4)(5)(6)(7). In hemoglobin H disease, the young cells contain more soluble hemoglobin H, whereas inclusions of precipitated beta chains are detected in the older cells (1,4,8,9).…”

Protein synthesis in a cell free human reticulocyte system: ribosome function in thalassemia.

“…This seems unlikely on the basis of several considerations. First, thalassemia major generally represents a chronic hemolytic state with as marked erythroid hyperplasia as that encountered in any of the chronic hemolytic anemias to which it is being compared (25). Second, the ribosome and polyribosome content per reticulocyte is not significantly different in the cells of thalassemic and nonthalassemic subjects.…”

Introduction of David G. Nathan, MD

“…Together David and Frank described the red cell abnormalities observed in pyruvate kinase deficiency (3-6) and the rare but fascinating defects that follow excessive monovalent cation permeability (7)(8)(9)(10). During that period David also became fascinated by the thalassemia problem (11,12) and with a then Harvard Medical student, the late Robert Gunn, wrote a classic paper that brought attention to the role of unbalanced hemoglobin synthesis in the pathogenesis of the anemia (13). David and I picked up on this theme in a paper noting that the genetic defect in the production of a single globin peptide produced a clinical syndrome of hyperproliferation (14).…”