Abstract 168

Osteopetrosis, or marble bone disease, is an inherited disorder of bone formation characterized by decreased bone resorption, resulting in dense, fragile bones. In the neonatal presentation, patients usually manifest hepatosplenomegaly, leukocytosis, lymphadenopathy, thrombocytopenia, and, occasionally, anemia. Although anemia and thrombocytopenia in these patients are thought to be due to hypersplenism and extravascular hemolysis, the exact pathogenesis has not yet been confirmed. Tpo, a physiologic regulator of platelet production, is decreased in the blood of patients with thrombocytopenia due to platelet destruction, whereas it is increased in thrombocytopenic patients with megakaryocyte deficiency. Thus, measurements of Tpo levels may be useful to discern the underlying mechanism of decreased platelet counts. In order to shed light on the mechanisms of thrombocytopenia in osteopetrosis, we serially assessed, by ELISA, plasma. Tpo concentrations in a term newborn infant who was diagnosed with osteopetrosis on the basis of typical skeletal lesions, hepatosplenomegaly, anemia, and thrombocytopenia(90×103/mm3). Treatment with prednisone (1 mg/kg/d) was established starting on day 3 of life. The figure shows reciprocal changes in plasma Tpo levels and platelet counts on different days of life. Tpo increased to 2,533 pg/ml at the nadir of the platelet count and decreased as platelets increased. However, after the recovery Tpo was still exceedingly above normal. These data indicate an inverse correlation between Tpo levels and platelet counts in osteopetrosis. This suggests that megakaryocyte deficiency is an important contributor to thrombocytopenia in this condition.Figure

figure 1

Figure 1