The limit of hemoglobin synthesis in hereditary hemolytic anemia

The Anemia of Liver Disease: Observations on Its Mechanism 1

“…This is in contrast to the distribution of Crp5 following the injection of CrP1-tagged hemoglobin solutions, and suggests that the spleen is the major site of red cell destruction in patients with cirrhosis and anemia. The correlation present between the rate of red cell detruction and a maintained degree of anemia implies that the production of hemoglobin by the marrow is proportional to the degree of anoxia and approaches a maximum as anoxic stimulation increases, rather than reaching a maximum beyond which anemia commences, as has been implied by Crosby and Akeroyd (43).…”

Control of marrow production by the level of iron supply

“…Crosby (12) demonstrated a maximum marrow production response of three to six times normal in a single individual undergoing rapid phlebotomy for treatment of hemochromatosis. In hemolytic anemia patients he was able to show a similar level of maximum marrow production (7).…”

“…Whereas the iron delivered from normal reticuloendothelial stores or orally administered iron is sufficient for a marrow production response of only two to three times normal, the increased iron supply from nonviable red cells, hemolysis, or iron dextran infusions permits marrow production to rise acutely to levels of four to eight times normal. INTRODUCTION Although erythropoiesis has been extensively studied in a wide spectrum of disease states (1)(2)(3)(4)(5)(6)(7), there have been very few studies of the characteristics of the normal marrow response to varying degrees of anemia (8)(9)(10)(11)(12)(13)(14)(15). The wide variation in the level of red cell production which occurs with different anemias has been considered to be a function of both the relative level of hematocrit depression and a variety of biochemical abnormalities and cofactor deficiencies which interfere with cell growth and maturation.…”

Hypocatalasemia: A New Genetic Carrier State*

“…However, in individuals heterozygous for the gene responsible for hemoglobins S or C, only 30 to 40 per cent of the hemoglobin is of the abnormal type (41,42). Individuals homozygous for either of these genes, with all the hemoglobin abnormal, have a significantly decreased hematopoietic reserve (43,44). This leads to the conclusion that a probably quite minor change in a gene, so small as to result in a single amino acid substitution in a protein, may at the same time very significantly reduce what may roughly be termed "gene efficiency," i.e., as judged by the quantity of end product (45).…”