Haemolytic Anaemia in Osteopetrosis

The anaemia so frequently found in cases of osteopetrosis in children has been generally regarded as being due to poor development of the bone marrow cavity by failure of absorption and organization of primitive chondro-osteoid tissue (Warkany, 1959; Clifton and Frank, 1959; Aegerter and Kirkpatrick, 1958). In many cases, however, the severity of the anaemia has not corresponded with the radiological appearances of the medullary cavity, and alternative theories have been put forward to explain this discrepancy. Some workers have suggested that the anaemia is due to a primary bone marrow defect (McCune and Bradley, 1934), and others (Creveld and Heybroek, 1940) have postulated that the bone lesions and the anaemia are both part of a common developmental mesenchymal disturbance. Hepatosplenomegaly, a common feature of this disorder, has been taken to indicate increased extramedullary erythropoiesis, and in view of this, splenectomy in cases of osteopetrosis is considered therapeutically unsound. Recently, however, doubt has been thrown on the above beliefs, and evidence is now accumulating that although the spleen in osteopetrosis may be a site of blood formation, blood destruction is also actively taking place in this organ. Increased destruction of red cells was demonstrated by Zetterstrom (1957) when he found a reduced survival time of red cells tagged with radioactive chromium in a 10-year-old patient with osteopetrosis. Engfeldt, Karlberg and Zetterstrom (1955) demonstrated a reduced red cell survival time of the patient's and donor's cells in a child of 6 years. Sjolin (1959) noted a constant excess of nucleated red cells in the blood of four patients, and this, together with the presence of reticulocytosis, thrombocytopenia, and the absence of demonstrable haemolysing antibodies, led him to conclude that haemolysis and hypersplenism occurred in osteo-