Studies on the metabolism of B12 and folic acid were performed in patients with heavy hookworm infection and severe iron deficiency anemia, and in patients with light infection, noninfected patients and normal subjects. Patients with heavy hookworm infection showed a marked decrease of the serum B12 as compared with normal subjects. Eight of 21 cases studied showed values of serum B12 below 100 µµg./ml. Twelve of 13 patients with severe hookworm infection showed impairment of the pteroylglutamic acid intestinal absorption; however, none of them exhibited megaloblastic proliferation in the bone marrow. They all recovered with iron therapy alone. The patients with light infection and the noninfected patients with iron deficiency anemia did not demonstrate significant differences from the normal subjects studied.
Morphology of the peripheral blood and bone marrow, iron, folic acid and vitamin B12 metabolism and estimation of erythrokinetics have been made in 17 patients with megaloblastic anemia of pregnancy. The peripheral blood showed the classic picture of megaloblastic anemia of pregnancy previously reported. Nine cases exhibited megaloblastic series in the marrow and 8 cases intermediate megaloblastic series. Folic acid malabsorption was observed in 12 cases. The malabsorption was still present after remission in 6 of 7 cases studied. Folic acid induced complete or partial remission in all the cases but one. In cases with partial remission iron deficiency anemia developed and responded adequately to iron therapy. The average of the serum level of vitamin B12 showed a diminution of approximately 39 per cent below normal level. Normal pregnant women belonging to the same social condition of the patients and well-to-do pregnant women showed the same reduction. The erythrokinetics demonstrated that megaloblastic hyperplasia and iron turnover values do not correlate with the reticulocyte count. This indicates that the marrow activity was ineffective in terms of red cell production. This marrow dysfunction was associated with an increased rate of red cell destruction: approximately 4 times normal. The clinical and laboratory data collected suggest the division of megaloblastic anemia cf pregnancy into two types: pure megaloblastic anemia of pregancy, and megaloblastic anemia associated with iron deficiency. The morphologic characteristics, the amount of hemosiderin contained in the bone marrow, the reticulocyte count, plasma iron, T ½ plasma iron clearance, plasma iron turnover, and response to treatment may permit one to separate one type from another.
Iron metabolism, balance of red cell production and destruction and iron absorption from hemoglobin were determined in 11 patients with heavy hookworm infection and severe anemia. The plasma iron, total iron binding capacity, bone marrow hemosiderin and plasma Fe59 clearance are in agreement with the idea that the anemia associated with hookworm infection is of the iron deficiency type. The rate of red cell production measured by the E/M ratio, absolute reticulocyte count and plasma iron turnover showed an increase to about twice normal, while the rate of destruction estimated by the T ½ erythrocyte survival showed a destruction about 5 times normal. This unbalance between production and destruction could explain the severity of the anemia. The increase of fecal urobilinogen output to twice normal was interpreted as due to the metabolism of the hemoglobin lost into the intestine rather than to an increase of hemolysis. The estimation of fecal blood loss in the patients whose red cells were tagged with Cr51 and Fe59, showed that the radioactivity counted with Fe59 was only about 63 per cent of the radioactivity counted with Cr51. This difference was interpreted as due to iron absorption from the hemoglobin lost into the intestine. The mean daily fecal excretion of iron reaches 4.7 mg. Since the iron metabolism in these patients is in equilibrium, we have concluded that the iron loss is replaced by the iron from food; this is in addition to the 3 mg. hemoglobin iron which is reabsorbed from the blood lost into the gut.
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