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Quantitative information on abnormalities of erythropoiesis and mechanisms of anaemia has been obtained in 136 anaemic patients by means of ferrokinetic studies. To derive a functional classification of anaemia based on ferrokinetic parameters, agglomerative hierarchical cluster analysis and principal coordinate analysis were utilized as techniques for unsupervised classification. Two main clusters were found and named anaemia with low potential erythropoiesis and with high potential erythropoiesis, since the most discriminant parameter between them was total erythroid iron turnover, a measure of total erythropoietic activity. A value of total erythropoiesis equal to 4 times the normal was found to discriminate these two types of anaemia in 94% of cases. Within the group with low potential erythropoiesis, three clusters showing different qualitative disturbances of erythropoiesis were singled out. Among patients with high potential erythropoiesis, two clusters were found. A value of effective erythropoiesis equal to 2.5 times the normal was shown to have a high discriminant power between these clusters. This threshold level distinguished between patients having ineffective erythropoiesis or peripheral haemolysis as the major mechanism of anaemia. The present functional classification of anaemia provides a complete picture of the different pathogenetic mechanisms and may represent the basis for a more rational diagnostic approach to erythroid disorders.

Ferrokinetic parameters were estimated in eight patients with primary acquired sideroblastic anaemia (PASA) by means of a mathematical model of iron kinetics. Both plasma 59Fe clearance and red cell utilization curves were used to identify the model parameters. The close agreement between experimental and theoretical data proved that the model can describe iron kinetics in sideroblastic anaemia. Ineffective erythropoiesis was found to be major factor in the production of the anaemia. Various degrees and patterns of peripheral haemolysis were observed. The storage iron was always markedly increased and a large non-erythroid iron turnover was calculated in the most severely affected patients. The results are compared with present knowledge of erythropoiesis in PASA.

Ferrokinetic studies were carried out in 8 patients with heterozygous beta-thalassaemia with anaemia of varying severity. Effective and ineffective erythropoiesis, mean red cell lifespan and non-erythroid iron turnover were estimated from the experimental data through a mathematical model of iron kinetics. Erythropoietic activity was markedly increased in all patients, but was variably ineffective (from 10 to 74%). A negative correlation (r = 0.855, P less than 0.01) was found between the amount of ineffective erythropoiesis and Hb level. Red cell lifespan was variably shortened and there was a negative correlation between the degree of daily peripheral haemolysis and Hb level (r = 0.733, P less than 0.05). Non-erythroid iron turnover was increased in most patients. The results provide quantitative measurements of the mechanisms responsible for the wide variation of the Hb level in heterozygous beta-thalaeeaemia. Ineffective erythropoiesis seems to be the major reason for the anaemia. Peripheral haemolysis contributes to it, especially in the most severely affected patients. The increased non-erythroid iron turnover may be responsible for the pathology which characterizes heterozygotes in the adult life.

Erythrokinetic parameters were estimated in six patients suffering from congenital dyserythropoietic anaemia type II (CDA II) by means of a mathematical model of iron kinetics. A wide variation in effectiveness of erythroid activity was observed, and a significant negative correlation was found between ineffective erythropoiesis and peripheral haemolysis. In four patients with prominent peripheral haemolysis, splenectomy was carried out. Marked improvement in their clinical condition and in haemoglobin level resulted.