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.

Romiplostim administration shows reduced megakaryocyte response-capacity and increased myelofibrosis in a mouse model of MYH9-RD

“…4,5 Second-generation thrombopoietic agents, which stimulate megakaryocytopoiesis by binding to the thrombopoietin (TPO) receptor, 6 may be an option for increasing the platelet count in MYH9-RDs. Two of these TPO receptor agonists have completed phase 3 trials in primary immune thrombocytopenia (eltrombopag, a nonpeptide TPO receptor agonist, and romiplostim, a peptide TPO receptor agonist 7,8 ) and have been recently approved in several countries for treatment of certain patients with immune thrombocytopenia.…”

“…4,5 Second-generation thrombopoietic agents, which stimulate megakaryocytopoiesis by binding to the thrombopoietin (TPO) receptor, 6 may be an option for increasing the platelet count in MYH9-RDs. Two of these TPO receptor agonists have completed phase 3 trials in primary immune thrombocytopenia (eltrombopag, a nonpeptide TPO receptor agonist, and romiplostim, a peptide TPO receptor agonist 7,8 ) and have been recently approved in several countries for treatment of certain patients with immune thrombocytopenia.Eltrombopag administration has recently been tested in patients with MYH9-RDs in a phase 2, multicenter trial, showing moderate increase in platelet counts and reduction in bleeding tendency, 9 suggesting that these new thrombopoietic agents could also represent an interesting therapeutic option for patients with MYH9-RDs. However, platelets in MYH9-RDs differ from platelets in idiopathic thrombocytopenic purpura, and it is unknown whether stimulation of megakaryocytopoiesis by TPO receptor agonists may cause additional changes in these MYH9-RD platelets.…”

Risk of Thromboembolism in Patients with Immune Thrombocytopenia

“…They promote megakaryocyte differentiation, proliferation, and platelet production [50]. In these patients with ITP treated with TPO-R agonists, a significant number of TEEs has been reported (0 to 6.7%) [51][52][53][54][55][56][57][58][59][60][61][62][63] ( Table 2).…”

Primary antiphospholipid syndrome patient associated with refractory thrombocytopenia and Factor V Leiden mutation treated with eltrombopag

“…Son yillarda refrakter İTP tedavisinde kullanilan yeni bir ilaç grubu TPO ( trombopoetin) reseptör agonistleridir. Bu grupta yer alan ve şu anda dünyada ruhsatli olarak kullanilan iki ilaç Romiplostim ve Eltrombopag, TPO reseptörünü aktive ederek trombosit yapimini arttirir [18]. İTP tedavisinde eltrombopag tedavisine yanit oranlari %80 civarindadir [19][20][21].…”