Hookworm Anemia: Iron Metabolism and Erythrokinetics

Iron metabolism, balance of red cell production and destruction and ironabsorption from hemoglobin were determined in 11 patients with heavy hookworm infection and severe anemia.

The plasma iron, total iron binding capacity, bone marrow hemosiderinand 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 twicenormal, while the rate of destruction estimated by the T erythrocytesurvival showed a destruction about 5 times normal. This unbalance betweenproduction and destruction could explain the severity of the anemia.

The increase of fecal urobilinogen output to twice normal was interpretedas due to the metabolism of the hemoglobin lost into the intestine rather than toan increase of hemolysis.

The estimation of fecal blood loss in the patients whose red cells weretagged with Cr⁵¹ and Fe⁵⁹, showed that the radioactivity counted with Fe⁵⁹was only about 63 per cent of the radioactivity counted with Cr⁵¹. This difference was interpreted as due to iron absorption from the hemoglobin lostinto the intestine.

The mean daily fecal excretion of iron reaches 4.7 mg. Since the ironmetabolism in these patients is in equilibrium, we have concluded that theiron 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.

Submitted on January 9, 1961 Accepted on April 2, 1961     

Relation Between Severity of Anemia and Erythropoietin Titer in Human Beings

Patients with severe hematologic disorders may have elevated erythropoietintiters in plasma or urine at higher hemoglobin concentrations than those associated with elevated titers in experimental animals or patients anemic as aresult of simple blood loss. Patients with "primary" hematologic disease mayhave a measurable titer of erythropoietin in the plasma and urine at hemoglobinconcentrations up to 8 Gm./100 ml., but patients with iron-deficiency anemiashow elevated titers in the urine only with hemoglobin concentrations at orbelow 4 Gm./100 ml. and in the plasma below 5 Gm./100 ml. The abruptnesswith which the titer rises and the severity of the anemia required beforemeasurable titers appear are similar in man and in rabbits, sheep and dogs.The fact that no measurable erythropoietin titer can be demonstrated whenthe hemoglobin concentration is well below that required for intense stimulation of erythropoiesis and the abruptness of the rise at hemoglobin concentration of 4 Gm./100 ml. or less suggest that erythropoietin may not bean important factor in the control of erythropoiesis except in extreme circumstances. On the other hand, these facts may be explained more simply by theinsensitivity of the assay methods used.

Submitted on March 13, 1961 Accepted on May 6, 1961     

Genetics of the HL-A System in a Venezuelan Heterogeneous Population

Abstract. HL-A antigen and gene frequencies of 206 unrelated adults living in the cities of Caracas and Maracaibo have shown that this heterogeneous Venezuelan population sample possess 11 specificities of the first (LA) HL-A series and 15 specificities of the second (Four) series. HL-A2, HL-A9, HL-A5 and W5 showed frequencies higher than those observed in Caucasoid populations. The most frequent haplotypes were 2, W5; 2, 5; 9, 12; 2, 12 and 2, X₂. No outstandingly high value for gametic association between the alleles of the 2 HL-A series was observed, but haplotypes formed by antigens with dissimilar frequencies in Caucasoids, Negroids and American Indian tribes have shown statistically significant D values. Genetic distance calculated using the HL-A system alone showed that this population is closer to the average Caucasoid and Negroid populations tested at the 5th International Histocompatibility Workshop than to 2 American Indian tribes living in the same country.     

Y-chromosome biallelic polymorphisms and Native American population structure

It has been proposed that women had a higher migration rate than men throughout human evolutionary history. However, in a recent study of South American natives using mtDNA restriction fragment polymorphisms and Y-chromosome microsatellites we failed to detect a significant difference in estimates of migration rates between the sexes. As the high mutation rate of microsatellites might affect estimates of population structure, we now examine biallelic polymorphisms in both mtDNA and the Y-chromosome. Analyses of these markers in Amerinds from North, Central and South America agree with our previous findings in not supporting a higher migration rate for women in these populations. Furthermore, they underline the importance of genetic drift in the evolution of Amerinds and suggest the existence of a North to South gradient of increasing drift in the Americas.     

Recovery of blood group antibodies from erythrocyte powder

A powder from dried human erythrocyte stromata was prepared todetermine whether normal autoantibodies could be recovered from unsensitized erythrocyte powder and to study some of the properties of anti-A,anti-B and anti-Rh_o(D) antibodies recovered from sensitized powder.

Twenty-five samples of unsensitized erythrocyte powder of all ABO bloodgroups were tested. The amount of eluted powder was as great as 200 mg.,representing about 25 ml. of packed red cells. In no instance could antibodybe detected in the eluates. This negative finding could be explained in threeways: by lack of antibody production, in disagreement with Landsteiner’srule; by neutralization of antibody by a corresponding antigen before itreached the circulation; or by immediate elimination of sensitized erythrocytesfrom the circulation.

The eluate of A erythrocyte powder sensitized with O serum agglutinatedboth A and B red cells. After neutralization with A polysaccharides, theanti-A antibody disappeared and anti-B remained. These experiments appearto support the theory of the multispecific character of natural antibodies.

Rh-positive erythrocyte powder was sensitized with an incomplete anti-D(anti-Rh_o) serum and eluted in saline. The eluate did not agglutinate Rhpositive cells, but sensitized them for the action of Coombs’ serum. The mixture of Coombs’ serum with the eluate also produced agglutination of Rh-positive cells. These phenomena are explained as being due to the lack of orthe very small amount of ballast proteins in the saline eluate.

Submitted on May 14, 1958 Accepted on February 27, 1959