Current and emerging treatments based on novel mechanisms for immune thrombocytopenia
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rrent and emerging treatments based on novel mechanisms for immune thrombocytopenia 1,2,3,4
Qiaozhu Zeng 1
& Xiaohui Zhang
1,2,3,4*
Peking University People’s Hospital, Peking University Institute of Hematology, Beijing 100044, China; 2 Collaborative Innovation Center of Hematology, Peking University, Beijing 100044, China; 3 Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China; 4 National Clinical Research Center for Hematologic Disease, Beijing 100044, China Received April 11, 2020; accepted June 16, 2020; published online August 7, 2020
Citation:
Zeng, Q., and Zhang, X. (2020). Current and emerging treatments based on novel mechanisms for immune thrombocytopenia. Sci China Life Sci 63, https://doi.org/10.1007/s11427-020-1757-2
Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by increased platelet destruction and impaired platelet production. The pathophysiology of ITP is complicated and incompletely understood. It is traditionally recognized that antibody-coated platelets are prematurely cleared via Fc-independent or dependent mechanism in the spleen, liver, or both. Antibody-mediated complement activation and desialylation can also destroy platelets. In addition, antibodies can inhibit megakaryocyte production and maturation. Abnormalities in cellular immunity have also been described, including skewing of T helper (Th) cells toward a type 1 T helper (Th1) and type 17 T helper (Th17) phenotype, reduction of regulatory T-cell activity, and an increase in cytotoxic T cells. Corticosteroids, intravenous immunoglobulin (IVIG), and anti-D are recommended as the standard first-line/initial treatments. However, only 30% to 50% of adult patients have a sustained response after glucocorticoids are discontinued. For ITP patients who do not have an initial response to glucocorticoids or who have recurrent decreases in platelet counts after glucocorticoids are discontinued, second-line/ subsequent treatments are needed, including thrombopoietin receptor agonist (TPO-RA), immunomodulators, and splenectomy. Besides, in recent years, many new drugs have also emerged in the management of ITP. Dosage, efficacy, safety, and principles of these treatments for ITP are summarized in *Corresponding author (email: [email protected])
Table S1 in Supporting Information. Mechanisms of action and advanced findings of TPO-RAs. In 2008, romiplostim and eltrombopag were licensed in the US for the treatment of primary ITP patients not responsive to or relapsing after first-line/initial treatment. Avatrombopag was approved in 2019 for the treatment of adults with chronic ITP. Increasing use of TPO-RAs in newly diagnosed and persistent ITP is also presented with more input from available real-world data. TPO-RAs bind to the TPO receptor, resulting in its conformational change, activation of the JAK2/STAT5, PI3K/AKT, and ERK pathway, thus an increase of megakaryocyte progenitor proliferation and platelet production. They have immunomodulatory effects on regulatory T and B
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