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 ma rrow megakaryocytes. This similar to 90 kd protein has recently been i solated and is comprised of an erythropoietin domain that is similar t o 50% homologous to erythropoietin and a carbohydrate domain that is h ighly glycosylated and appears to stabilize the protein in the circula tion. Thrombopoietin is produced in the liver and blood levels are det ermined by the mass of circulating platelets. However, there is no pla telet ''sensor.'' Rather platelets contain high affinity thrombopoieti n receptors that bind and remove thrombopoietin from the circulation a nd thereby directly determine circulating levels. In vitro thrombopoie tin 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 w ithout affecting other lineages. However, when given to animals follow ing chemotherapy or irradiation, it stimulates erythroid and myeloid a s well as platelet recovery. Several different recombinant thrombopoie tin proteins are now entering clinical trials in humans and all prelim inary reports confirm a potent thrombopoietic stimulus and apparent la ck of toxicity. Thrombopoietin shows great promise in preventing the t hrombocytopenia associated with chemotherapy, bone marrow transplantat ion, and other acute or chronic thrombocytopenic disorders. In transfu sion medicine, thrombopoietin may help mobilize peripheral blood proge nitor cells, stimulate donors for plateletpheresis, and enhance platel et survival and function during storage. Many studies are currently un derway in all these areas and should soon establish the role of thromb opoietin in clinical medicine. (C) 1996 Wiley-Liss, Inc.