Circulating thrombopoietin concentrations in thrombocytopenic patients, including cancer patients following chemotherapy, with or without peripheral blood progenitor cell transplantation

Authors


Y. Gloria Meng Genentech Inc., 460 Point San Bruno Boulevard, South San Francisco, CA 94080, U.S.A.

Abstract

Thrombopoietin, the ligand for the c-mpl receptor, promotes proliferation and maturation of megakaryocytes. An ELISA using a chimaeric receptor, mpl-IgG, for capture, and rabbit antibody to thrombopoietin for detection was developed for the quantitation of thrombopoietin in human serum or plasma. This ELISA preferentially detects full-length thrombopoietin compared to the bioactive N-terminal half of the molecule which has homology to erythropoietin. Thrombopoietin was not detected (<0.16 ng/ml) in 88/89 healthy individuals. However, elevated thrombopoietin concentrations of up to 3 ng/ml were detected in 59/63 thrombocytopenic patients, including cancer patients following chemotherapy. In cancer patients receiving chemotherapy with (n = 12) or without (n = 6) peripheral blood progenitor cell transplantation, thrombopoietin concentrations varied inversely with platelet counts throughout the treatment period. In general, patients who received myeloablative chemotherapy on days −7 to −2 and peripheral blood progenitor cell transplantation on day 0 had high thrombopoietin levels (0.6–2.9 ng/ml) around day 5. Low platelet counts (<20 × 109/l) occurred between days 4 and 9. Patients who received high-dose chemotherapy on day 1 (equivalent to day −7 for transplantation patients) to day 6 without transplantation had high thrombopoietin concentrations (1.4–2.3 ng/ml) around day 13 and low platelet counts occurred between days 7 and 17.

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