Thrombopoietin: biology, clinical applications, role in the donor setting

Thrombopoietin (c-Mpl ligand) is the hematopoietic growth factor that is responsible for regulating the production of platelets from bone marrow megakaryocytes. This approximately 90 kd protein has recently been isolated and is comprised of an erythropoietin domain that is approximately 50% homologous to erythropoietin and a carbohydrate domain that is highly glycosylated and appears to stabilize the protein in the circulation. Thrombopoietin is produced in the liver and blood levels are determined by the mass of circulating platelets. However, there is no platelet "sensor." Rather platelets contain high affinity thrombopoietin receptors that bind and remove thrombopoietin from the circulation and thereby directly determine circulating levels. In vitro thrombopoietin stimulates both early and late megakaryocyte precursors as well as some erythroid and multipotential progenitor cells. When administered to normal animals, it stimulates platelet production up to six-fold without affecting other lineages. However, when given to animals following chemotherapy or irradiation, it stimulates erythroid and myeloid as well as platelet recovery. Several different recombinant thrombopoietin proteins are now entering clinical trials in humans and all preliminary reports confirm a potent thrombopoietic stimulus and apparent lack of toxicity. Thrombopoietin shows great promise in preventing the thrombocytopenia associated with chemotherapy, bone marrow transplantation, and other acute or chronic thrombocytopenic disorders. In transfusion medicine, thrombopoietin may help mobilize peripheral blood progenitor cells, stimulate donors for plateletpheresis, and enhance platelet survival and function during storage, Many studies are currently underway in all these areas and should soon establish the role of thrombopoietin in clinical medicine.