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Thrombopoietin: Platelets on Demand
- University of Washington, Seattle, WA 98195 Acknowledgment: The author thanks all of his collaborators who contributed to studies of thrombopoietin biology. Grant Support: In part by grants R01 DK 43719, R01 CA 31615, and R01 DK 49855 from the National Institutes of Health. Requests for Reprints: Kenneth Kaushansky, MD, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195.
We are still without a trustworthy medicine which can always be relied upon to control purpura.
Sir William Osler, 1892
In many respects, this dilemma is as poignant today as it was when it was first penned by the famous physician. Severe thrombocytopenia complicates the course of many patients with naturally occurring or iatrogenic states of bone marrow failure. Because more patients with cancer are now undergoing stem cell transplantation and aggressive therapy, the transfusion of platelet concentrates now exceeds that of red blood cells. Unfortunately, many problems often arise in patients receiving platelet transfusions; these include a high incidence of adverse reactions, refractoriness to subsequent platelet transfusions, and high costs. Accelerated recovery of the patient's own platelet production would obviously be highly desirable. Unfortunately, until only recently, our understanding of thrombopoiesis lagged far behind our understanding of other blood cells.
Ever since James Homer Wright began to stain blood smears and noticed a small disc-shaped cytoplasmic fragment, which he termed a blood plate [1], physicians have sought to understand the regulation of platelet production. Pioneering work in the early 1960s and 1970s provided a hierarchical model of stem cell maturation and the in vitro assays necessary to characterize and purify some of the humoral regulators of this process. These events, which shaped hematopoietic research for three decades, have yielded impressive results. With the cloning of erythropoietin [2] and granulocyte colony-stimulating factor (G-CSF) [3] in the mid-1980s, the hormones primarily responsible for erythrocyte and neutrophil production became available for clinical use. However, notably absent from these physiologic and biotechnical success stories was an understanding of platelet production and the hormone that was thought to be the primary regulator of the process: thrombopoietin.
The term thrombopoietin was first used by Kelemen in 1958 to describe the humoral substance responsible for …
