Abstract
In recent years, great advances have been made in elucidating the pathogenesis of thrombocytopenia and the mechanisms of thrombopoiesis. Drawing upon decades of basic science and clinical research, the pathways behind the immune-mediated destruction of platelets have opened new avenues. This has led to the application of safer and more efficacious immunosuppressive agents, such as the anti-CD20 monoclonal antibody rituximab, or potentially altering the co-stimulatory pathways of the immune system with an anti-CD40L (CD154) monoclonal antibody. This has been coupled with the discoveries of the genetic and molecular pathways in thrombopoiesis, including the identification and cloning of thrombopoietin (TPO) and its receptor. The use of recombinant TPO, such as PEG-rHuMGDF and rhTPO, to treat thrombocytopenia have paved the way for alternative peptidyl and nonpeptidyl thrombopoietic agents that are considered to be nonimmunogenic. Those that have undergone evaluation in humans include the Amgen megakaryopoiesis protein (AMG) 531 compound, eltrombopag, and AKR-501. Additional TPO mimetics show promise in vitro and await future development.
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