R. L. Verwilghen

Ineffective Erythropoiesis with Morphologically Abnormal Erythroblasts and Unconjugated Hyperbilirubinaemia

Four cases of congenital dyserythropoietic anaemia in two families are described. The evidence for a dyserythropoietic state is discussed and the suggestion made that the hyperbilirubinaemia of the unconjugated type is mainly due to intramedullary bilirubin formation. Many abnormal multinucleated erythroblasts were found in the bone marrow. The evidence for a membrane defect and a possible haemoglobin abnormality have been presented.

DYSERYTHROPOIESIS AND DYSERYTHROPOIETIC ANAEMIA

When, for one or other reason, haemopoiesis is disturbed it may at times be difficult to know how to describe the phenomenon which has occurred, especially if the disturbance is both quantitative and qualitative. The random use of such terms as aplasia, hypoplasia, dyshaemopoiesis, dyserythropoiesis and dyserythropoietic anaemia may give rise to confusion. It would seem rational to use the terms aplasia and hypoplasia to describe conditions in which there is a quantitatively decreased haemopoiesis, so that the bone marrow produces and releases an insufficient number of blood cells into the circulation. Dysplasia, on the other hand, would describe the situation where there is a qualitative abnormality of the bone marrow. This may result in inefficient or ineffective haemopoiesis or, if limited to the erythroid cells (i.e. dyserythropoiesis), in ineffective erythropoiesis. It implies either a defect primarily of a stem cell with consequent abnormality of development of the cell line or lines, or an abnormal environmental state within the bone marrow which inhibits normal cell proliferation, or a combination of both factors. In practice hypoplasia alone is the exception rather than the rule and aplastic anaemia is usually accompanied by dysplasia. Dysplasia may occur in a wide range of diseases which primarily affect either the nucleus or the cytoplasm of the erythroblast. It is present in megaloblastic anaemias, thalassaemia and erythroleukaemia. A dyserythropoietic component of greater or lesser severity occurs in aplastic anaemia, myelosclerosis, iron deficiency and iron utilization defects, including acquired sideroblastic anaemias, and in infections (Lewis, 1969; Dreyfus et a!, 1969a). It also occurs as a congenital disorder (Crookston et al, 1969; Verwilghen et al, 1969), and (? rarely) as a primary acquired defect (Lewis, 1969, 1972). The term dyserythropoietic anaemia should be confined to these congenital and acquired primary cases in order to distinguish them from the dysplasia which is associated with identifiable diseases. Congenital sideroblastic anaemias might be included in this group. It is important to correlate morphological and functional aspects of dysplasia and to establish diagnostic criteria for making the diagnosis of dyserythropoietic anaemia.

Quantitative Assessment of Erythropoiesis in Bone-marrow Expansion Areas Using Fe-52

Summary. Quantitative 52Fe scans were performed in 180 patients. Expansion of bone marrow was observed in 70. This bone marrow expansion was a nearly constant feature in haemolytic anaemia and in sideroblastic anaemia. It occurred in a third of the patients with myelofibrosis. In patients with polycythaemia rubra vera, expansion was noticed in only two out of seven. Erythropoiesis in expansion areas occurred despite persistence of fat in the iliac crest bone marrow biopsy. It could exist with a slight increase in erythropoiesis and might develop only after a long period of erythropoietic stimulation.Increased marrow activity can take place without erythropoietic expansion in long bones. The fraction of iron uptake in expansion areas did not exceed a third of total marrow iron uptake. With increasing erythropoiesis, the increase in iron uptake in expansion areas was less marked than the increase in the central areas. Erythropoiesis in expansion areas was usually not of major quantitative importance but could nevertheless reach the erythropoiesis of a normal adult.

Anabolic Agents and Relative Polycythaemia

after the administration of testosterone an increase in the haemoglobin concentration may occur, and the difference in haemoglobin concentration between males and females has been ascribed to this hormonal influence. This hypothesis has been confirmed experimentally by Kennedy (1962). An increase in the haemoglobin concentration has also been brought about by the administration of ‘anabolic’ drugs (Booij and Kuypers, 1962; Everse and Van Keep, 1962). Both testosterone and anabolic drugs have induced remissions in congenital and acquired aplastic anaemia (Kennedy and Gilbertson, 1957; Shahidi and Diamond, 1959, 1961; Kennedy, 1962). These authors also reported polycythaemia in some cases following treatment with androgens or anabolic drugs. Gardner and Pringle (1961) have described polycythaemia in a woman suffering from a tumour of the adrenal cortex. Booij and Kuypers (1962) reported two cases of polycythaemia after prolonged administration of Nandrolone‐phenylpropionate (Durabolin) at high dosage, and they also demonstrated that this drug had an erythropoietic action in rats. But, like most other workers they based their observations only on measurements on peripheral blood and they made no blood volume determinations. Thus they were unable to distinguish between an increase in haemoglobin concentration due to a decrease of the plasma volume and an absolute increase of the whole red cell mass. Kennedy (1957), however, observed a return to normal values of the red cell mass during treatment of breast cancer with testosterone and even an increase exceeding the normal values in some of the patients. Unfortunately no plasma volume determinations were made.

The spleen and haemolysis: evaluation of the intrasplenic transit time.

The mean intrasplenic red cell transit time (STT) and the slow mixing splenic red cell volume (SSV) have been measured in patients with hereditary spherocytosis (HS), autoimmune haemolytic anaemia (AIHA) and lymphoproliferative disease (LD). There was an inverse relationship between the mean red cell life span (MRCLS) and the STT in HS (r=–0·96, P<0·001) and in AIHA (r=–0·90, P<0·001). No such relationship existed in LD. The size of the spleen and the SSV were not related to the severity of haemolysis. Our data offer strong evidence for the conditioning effect of the spleen on HS‐ and AIHA red cells and suggest that the STT is an index of the adverse effect of the spleen on red cells in patients with HS or AIHA.