title: Thrombopoietic agents.
abstract: Thrombopoietin (TPO) is the key cytokine involved in thrombopoiesis, and is the endogenous ligand for the thrombopoietin receptor that is expressed on the surface of platelets, megakaryocytes, and megakaryocytic precursors. First-generation thrombopoietic agents were recombinant forms of human TPO, and their development was discontinued after prolonged thrombocytopenia due to neutralizing auto-antibodies cross-reacting with endogenous TPO was observed. Second-generation thrombopoiesis-stimulating molecules are now available, which have unique pharmacological properties and no sequence homology to endogenous TPO. Two of these new agents, romiplostim and eltrombopag, have already completed phase III trials in primary immune thrombocytopenia and have been granted marketing authorization for use in this disease. Phase II and III trials with these novel drugs are ongoing in other conditions characterized by thrombocytopenia, such as chemotherapy, chronic liver disease, and the myelodysplastic syndromes. Most of the other second-generation thrombopoietic growth factors are in early phase clinical development.
authors.affiliation: Department of Haematology, St George's Hospital, London, United Kingdom. Roberto.Stasi@stgeorges.nhs.uk
authors.forename: Roberto
authors.initials: R
authors.lastname: Stasi
authors.forename: Jenny
authors.initials: J
authors.lastname: Bosworth
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rhodes
authors.forename: Muriel S
authors.initials: MS
authors.lastname: Shannon
authors.forename: Fenella
authors.initials: F
authors.lastname: Willis
authors.forename: Edward C
authors.initials: EC
authors.lastname: Gordon-Smith
mesh_terms: D000818:Animals; D001565:Benzoates / Q000627:therapeutic use; D006801:Humans; D006834:Hydrazines / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D011961:Receptors, Fc / Q000627:therapeutic use; D053628:Receptors, Thrombopoietin / Q000819:agonists; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000188:drug therapy; D034061:Thrombopoiesis / Q000187:drug effects; D013926:Thrombopoietin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D001565:Benzoates; D006834:Hydrazines; D011720:Pyrazoles; D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins; D013926:Thrombopoietin; C488777:romiplostim; C520809:eltrombopag