I. Cavill

Iron stores in pregnancy.

Summary. Serum ferritin concentration has been measured during the course of pregnancy in 154 women. There was a rapid decrease in iron stores during early pregnancy irrespective of any iron therapy. Oral iron did, however, prevent the stores reaching iron deficient levels during the second half of pregnancy. The results suggest that maternal erythroid activity starts early in pregnancy and may exhaust the iron stores before the fetal demands for iron can be met.

Ferrokinetics and Erythropoiesis in Man: The Measurement of Effective Erythropoiesis, Ineffective Erythropoiesis and Red Cell Lifespan using 59Fe

Existing ferrokinetic methods do not provide a direct and quantitative measurement of effective and ineffective red cell production. A new method is described for calculating the daily uptake of iron by maturing red cells and the mean red cell lifespan. Ineffective erythropoiesis and non‐erythroid iron turnover are also measured. The method involves standard laboratory techniques but the analysis requires access to a computer. The preliminary results suggest that it will be a clinically useful tool for the investigation of erythroid disorders.

Erythropoiesis in pregnancy.

Summary. The reticulocyte count, serum ferritin and serum erythropoietin concentrations were measured during the course of pregnancy in 41 women. A decrease in iron stores early in pregnancy was accompanied by a significant rise in the reticulocyte count until the 28th week. Erythropoietin levels did not rise significantly until the 28th week of pregnancy and had fallen to the post‐natal level by 40 weeks. The results are consistent with an increase in erythropoietic activity early in pregnancy which did not appear to depend upon increased plasma erythropoietin levels.

Erythropoiesis and the Effect of Transfusion in Homozygous β-Thalassemia

THE erythropoietic abnormality in patients with homozygous β-thalassemia results from a genetically determined defect in globin (β-chain synthesis. Erythroid activity is vastly increased, and estim...

A Method for the Investigation of Reticuloendothelial Iron Kinetics in Man

Summary. A colloidal suspension of hydrolysed radio‐iron of high specific activity has been developed for the investigation of reticuloendothelial (RE) iron kinetics in man. Following intravenous injection this material is cleared rapidly by the RE system and the iron released into the plasma where it is bound to transferrin. There is no significant addition to the endogenous RE iron load, and it has proved possible to measure RE iron release without disturbing the normal iron flow.

Ferrokinetics and erythropoiesis in man: red-cell production and destruction in normal and anaemic subjects.

Recent advances in the analysis of plasma 59Fe clearance have produced a unified method for measuring effective and ineffective erythropoiesis (Ricketts et al, 1975). We have used this method to investigate the balance between red‐cell production and destruction in normal subjects and in patients with megaloblastic anaemia, iron deficiency anaemia and refractory hypoplastic anaemia. The results show that the normal marrow can maintain an appropriate red‐cell mass by altering red‐cell production to match destruction. In the anaemias we have studied there is an increased rate of either intra‐ or extra‐medullary red‐cell destruction. The response of the marrow may be limited by iron supply, by defective nuclear maturation or by some intrinsic marrow defect.

Erythropoiesis in the anaemia of rheumatoid arthritis

Erythropoietic activity and mean red‐cell lifespan were measured using 59Fe‐transferrin in 32 anaemic patients with active rheumatoid arthritis (RA) and in 20 haematologically normal subjects. Marrow iron turnover (MIT) in the patients was normal and in only 11 was red‐cell lifespan less than 70 d. Ineffective iron turnover (IIT) was significantly increased in those patients in whom there was evidence of iron deficiency (serum ferritin less than 12 μg/l) but in the remaining patients IIT was significantly less than in the normal subjects. In a further 19 patients with simple iron deficiency anaemia IIT was significantly increased. The marrow response to chronic inflammatory disease is clearly distinct from that seen in simple iron deficiency and this suggests different pathogenic mechanisms for these two anaemias.

THE REJECTED RETICULOCYTE

Erythropoiesis is a dynamic process: approximately 2 million new red cells are produced each second in adults. These cells emerge from the erythroblast population of the marrow without their nuclei but with a near complete complement of haemoglobin. Although the enucleate cells have lost most of their protein synthetic capabilities they retain a residuum of KNA. The polysomal remnants take on the appearance of a reticulum when stained supravitally. The eponymous reticulocytes loose this feature over the few days that they remain in the circulation. Their development towards mature erythrocytes also involves the loss of their residual RNA and may be accompanied by cell membrane and haemoglobin loss.

Ferrokinetics and Erythropoiesis in Man: An Evaluation of Ferrokinetic Measurements

The plasma iron clearance half‐time and plasma iron turnover have usually been interpreted as measures of total erythroid activity and the red‐cell utilization of 59Fe has been equated with effective red‐cell production. Erythrocyte iron turnover has sometimes been calculated as the product of plasma iron turnover and percentage utilization. We have assessed these measurements as estimates of erythroid activity by comparing them with total marrow iron turnover and red‐cell iron turnover determined by the method of Ricketts et al (1975) in 10 normal subjects and 51 patients with an uncomplicated haematological disorder. The results show that the plasma iron clearance half‐time does not reflect erythroid activity and that plasma iron turnover can be particularly misleading in patients with reduced marrow activity. Red‐cell utilization and erythrocyte iron turnover give a distorted reflection of effective erythropoiesis except in patients with erythroid hypoplasia. Marrow iron turnover and red‐cell iron turnover provide more realistic and generally applicable assessments of the degree and effectiveness of erythroid activity.

The Measurement of Red Cell Lifespan Using 59Fe

Summary. Red cell lifespan has been measured using 51Cr and 59Fe in 19 patients. 59Fe can be used to give results which agree closely with those obtained using 51Cr provided that the plasma 59Fe clearance curve is properly defined and the data analysed correctly. In some patients elution of 51Cr may be more than three times the normal level and the use of 59Fe may provide the only reliable estimate of red cell lifespan.