Fig. 3.--Series of cells from a case of severe progressive pernicious anemia of unknown etiology; preparation made two days antemortem: _a_, Nucleated red blood-corpuscles characterized as normoblasts by the intense staining of the nuclei; _a'_ and _a"_, karyokinetic figures in erythrocytes; the protoplasm finely punctate; _b_, beginning karyolysis in a megaloblast; _c_, erythroblasts with coarse granulation of the protoplasm; _d_, nuclear remains (?) and fine granulation of the protoplasm; _e_ and _f_, finely punctate red blood-corpuscles; _g_, megalocyte with two blue nuclei; nuclear remains (?) in the polychrome protoplasm. (Nothnagel-Lazarus.)] The red corpuscles show marked variation in size and shape (Plate VIII and Fig. 84). There is a decided {207} tendency to large oval forms, and despite the abundance of microcytes, the average size of the corpuscles is generally strikingly increased. Polychromatophilia and basophilic degeneration are common. Nucleated red cells are always present, although in many instances careful search is required to find them. In the great majority of cases megaloblasts exceed normoblasts in number. This ratio constitutes one of the most important points in diagnosis, since it is practically unknown in other diseases. Blood-plaques are diminished. The rare and rapidly fatal anemia which has been described under the name of _aplastic anemia_ is probably a variety of pernicious anemia. Absence of any attempt at blood regeneration explains the marked difference in the blood picture. Red corpuscles and hemoglobin are rapidly diminished to an extreme degree. The color index is normal or low. The leukocyte count is normal or low, with relative increase of lymphocytes. Stained smears show only slight variations in size, shape, and staining properties of the red cells. There are no megaloblasts, and few or no normoblasts. (2) Chlorosis.--The clinical symptoms furnish the most important data for diagnosis. The blood resembles that of secondary anemia in many respects. The most conspicuous feature is a decided decrease of hemoglobin (down to 30 or 40 per cent. in marked cases), accompanied by a slight decrease in number of red corpuscles. The color-index is thus almost invariably low, the average being about 0.5. As in pernicious anemia, the leukocytes are normal or decreased in number, with a relative increase of lymphocytes. {208} In contrast to pernicious anemia (and in some degree also to secondary anemia) the red cells are of nearly uniform size, are uniformly pale (Fig. 84), and their average diameter is somewhat less than normal. Changes in size, shape, and staining reactions occur only in severe cases. Erythroblasts are rarely present. The number of plaques is generally decreased.