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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.

The measurement of erythroid activity is based on the study of plasma iron kinetics. The radioiron injected should be bound specifically to transferrin, and the measurement of plasma 59Fe activity should be corrected for variation in plasma iron concentration. In addition, 59Fe-transferrin activity should be measured free of 59Fe-haemoglobin contamination. Analysis of the plasma 59Fe clearance curve over 14 days can give measures of total, effective and ineffective erythropoiesis, together with the red cell lifespan. Simpler ferrokinetic studies cannot be reliably used to assess erythropoiesis.

Ferrokinetic studies have fallen somewhat out of fashion and this is probably because T 1/2, PIT and percentage utilization give a poor reflection of the state of erythropoiesis. Recent advances have, however, enabled total, effective and ineffective erythropoiesis to be measured. The technique is simple but time-consuming, and analysis of the data requires access to computing facilities. Nevertheless, when bone marrow erythroid activity must be assessed these radioiron methods offer a rational approach.

1. The exchange of iron between plasma and erythroid and non-erythroid tissues was measured in 14 normal subjects, 17 iron-deficient patients, nine patients with primary idiopathic haemochromatosis and in 13 patients with haemolytic disorders. 2. The two main factors determining tissue iron turnover were shown to be the level of iron stores and the erythropoietic activity of the bone marrow.

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 amount and effectiveness of erythropoiesis was measured using 59Fe in 10 patients with the anaemia of chronic disease and in 10 iron deficient patients with a comparable degree of anaemia. In both conditions the anaemia was the result of the failure of the marrow to compensate for a modest degree of peripheral haemolysis but ineffective erythropoiesis was significantly greater in iron deficiency than in chronic disease. The results suggest that although the peripheral blood picture is similar in both conditions the anaemia of chronic disease cannot be attributed simply to iron deficient erythropoiesis.

Recently developed techniques for the investigation of iron kinetics were used to study the disturbance of iron metabolism in 19 untreated patients with Hodgkin's diseases (HD). The erythroid abnormality in newly diagnosed HD appears to be confined to those patients with systemic symptoms of weight loss, night sweats and fever, and consists of depression of marrow erythroid activity. These patients had a significnatly lower haemoglobin and serum iron concentration and a higher serum ferritin concentration, both when compared to normal subjects and to those patients with HD who lacked systemic symptoms. Ineffective erythropoiesis and red-cell destruction were not significantly increased. The present findings, confirm that HD patients with systemic symptoms have a depression of erythropoiesis, and that in these patients the marrow fails to respond to the stimulus of mild anaemia.

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.