The Anemia of the Di Guglielmo Syndrome (1959)

Abstract The physiopathology of the anemia of the Di Guglielmo syndrome (erythremic myelosis) was studied in 11 patients with the acute and chronic varieties of the disease. Ferrokinetic studies were performed in three additional patients. 1. The anemia was normochromic and macrocytic; in contrast to the mean corpuscular volume, which was elevated, the mean corpuscular hemoglobin was often normal. In several patients the mean corpuscular hemoglobin concentration was slightly lower than normal, suggesting slight hypochromia. 2. Reticulocytes were often increased but bore no relationship to the degree of the anemia nor to the shortening of the red cell life span. The reticulocyte count is an unreliable index of blood production in this disease. 3. The degree of erythroblastemia was highly variable. No direct correlation existed between the degree of erythroblastemia and the acuteness of the disease, nor was there any relationship between the degree of erythroblastemia and either the degree of anemia or the degree of erythrocytic destruction. 4. The bone marrow showed striking erythroblastic hyperplasia. This was usually of the megaloblastic type. Primitive erythroblasts (erythrogones) were conspicuous. The erythroblastic hyperplasia was out of proportion to the relatively minor reticulocytosis or the relatively slight diminution in red cell survival. 5. The nucleated red cells of the marrow showed variable numbers of megaloblasts and megaloblastoid forms, suggesting the presence of a vitamin B12 deficiency (pernicious anemia). However, the vitamin B12 concentration of the serum was elevated, and there was no response to the administration of vitamin B12 or folic acid. 6. Varying numbers of erythroblasts in the bone marrow and in the peripheral blood showed periodic acid-Schiff (PAS)-positive granules in the cytoplasm. No chemical abnormalities of hemoglobin could be detected either by the method of paper electrophoresis or by the alkali denaturation test. 7. Diminished red cell survival was present in most cases, but it was of a relatively slight degree. It was due to an "intracorpuscular" defect of the red cells. 8. The often great increase in fecal urobilinogen output as compared with a relatively minor rate of red cell destruction suggests "heme pigment diversion" or increased destruction of precursor red cells, as in pernicious anemia, where the same phenomenon has been observed. 9. The great increase in the number of erythroid cells in the bone marrow and the increased rate of iron turnover as compared with the relatively minor increase in red cell destruction and iron utilization point to an "ineffective" type of erythropoiesis. The high degree of "ineffective erythropoiesis" seen in this disease may be characteristic of the neoplastic proliferation of the red cell series. 10. In conclusion, the anemia of the Di Guglielmo syndrome is due to a combined disturbance: (1) an "ineffective" type of erythropoiesis of marked degree, perhaps due to an acquired (neoplastic) defect in the uptake or utilization of B12 by the erythroblasts and (2) increased hemolysis resulting from the increased destruction of defective red cells.