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This paper, by one of the legends of hematology, William Dameshek, and his colleague Edward Miller, is from the inaugural issue of Blood. By studying bone marrow specimens from controls, patients with acute or chronic immune thrombocytopenia, or patients with other thrombocytopenic disorders, the authors concluded that, in idiopathic thrombocytopenic purpura (ITP), production of platelets from megakaryocytes is defective, even while marrow megakaryocytes are greatly increased in number. This defect resolved after splenectomy. The authors appropriately credit E. Frank with having proposed defective platelet production from megakaryocytes in ITP in 1915. The idea that platelet production was defective in ITP was superseded or ignored for decades, but it has now been validated by the therapeutic effectiveness of the thrombopoietin mimetics in ITP.

A type of experimental hypersplenism characterized by splenomegaly and thrombocytopenia has been produced in the rat by the repeated intraperitoneal injection of methylcellulose. The urine of these animals was collected and given through a gastric tube to another group of normal rats for a period of 4 weeks. The results were a marked and rapidly developing thrombocytopenia, a delayed but definite anemia with mild reticulocytosis and leukocytosis. When the administration of urine was discontinued, the anemia regressed, but the thrombocytopenia persisted unmodified for 2 weeks. When the urine of hypersplenic rats was again given to this group for 6 additional weeks, it failed to induce anemia or to change the persistent thrombocytopenia. Intragastric administration of urine from normal rats, from rats made anemic by total body radiation and from the hypersplenic group after splenectomy to other groups of normal rats, failed to produce the same changes and only induced moderate leukocytosis. On the basis of these results, it is postulated that in experimental methylcellulose-hypersplenism in the rat there is a humoral factor(s) responsible for the thrombocytopenia, that this humoral factor(s) is eliminated in the urine and that when such urine is given to normal rats, it is responsible for the thrombocytopenia and partially for the anemia that are observed. Such factor(s) are in some important way related to the presence of the spleen.