Thrombopoietin.

By Shirley Ebbe I T HAS BEEN CLEAR for almost 20 years that platelet production is subject to homeostatic regulatory mechanisms that result in stimulation when the platelet count is li w’ and suppression when it is high.2 In spite of elapsed time, the physiologic processes that are involved in those regulatory mechanisms are not clear. Thrombocytopoiesis may be regulated by a humoral thrombopoietin, much as erythropoiesis is regulated by erythropoietin. This is an attractive hypothesis which seems to be gaining in popularity and for which there is some experimental support. The analogy implies that a low platelet concentration would cause a specific hormone, thrombopoietin, to be produced, that the hormone would stimulate megakaryocytopoiesis, and that production of the hormone would be suppressed by thrombocytosis. A number of investigators have found that the passive transfer of plasma or serum from thrombocytopenic animals or human beings to assay animals will result in increased production of platelets in the recipients. Two reports3’4 indicate that thrombopoietin is present in the blood of animals with a normal complement of plateleis and that its level is increased in those with thrombocytopenia. These results suggest that the normal rate of platelet production may be maintained by the constant stimulatory effect of thrombopoietin and support the concept that regulation is achieved by variation in the production ofthis hormone. It should be pointed out, however, that the site of production, stimulus for production, chemical nature, and mechanism of action of this proposed hormone are unknown. In some rodents, erythropoiesis ceases completely if the hematocrit is raised to less than twice normal. In spite of production of much larger increments in platelet count, platelet production has persisted, at a reduced rate, even though thrombopoietin has not been demonstrable in the plasma of the animals with transfusion-induced thrombocytosis.3’4 Thus, megakaryocytopoiesis may not be totally dependent on thrombopoietin. Alternatively, thrombopoietin production may not have been completely suppressed by the high platelet counts. When platelet production is stimulated experimentally by acute depletion of circulating platelets, a number of changes occur endogenously. Megakaryocytes increase in size, ploidy, number, and maturation rate. The platelets produced are of increased size, and an increase in the rate of platelet production is